Library

Landmark Trials

A curated reference of foundational trials in medicine — selected for clinical impact and teaching value.

Heart Failure

41 trials

A-HeFT

Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.

2004

AC01

Safety, pharmacokinetics, and exploratory efficacy of the oral ghrelin receptor agonist AC01 in heart failure with reduced ejection fraction (GOAL-HF1): a randomised, double-blind, placebo-controlled,

2026

AIRE

Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.

1993

ATTR-ACT

Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.

2018

CARE-HF

CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.

2005

CHAMPION

Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.

2011

CHARM-Added

Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.

2003

CHARM-Alternative

Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.

2003

CIBIS-II

Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.

1999

COMPANION

CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.

2004

CONSENSUS

Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.

1987

COPERNICUS

Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.

2001

DANISH

Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.

2016

DAPA

Letter by Qin et al Regarding Article “Dapagliflozin in Patients Hospitalized for Heart Failure: Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial and Meta-Analysis of Sodium-Glucos

2026

DAPA-HF

Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.

2019

DELIVER

Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.

2022

EMPEROR-Preserved

Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.

2021

EMPEROR-Reduced

Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.

2020

EMPHASIS-HF

Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.

2011

EPHESUS

Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.

2003

EXPLORER-HCM

Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.

2020

FINEARTS-HF

Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.

2024

GALACTIC-HF

Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.

2021

I-PRESERVE

Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.

2008

MADIT-CRT

CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.

2009

MADIT-II

Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.

2002

MERIT-HF

Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.

1999

PARADIGM-HF

Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.

2014

PIONEER-HF

Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.

2019

RAFT

CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.

2010

RALES

Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.

1999

SAVE

Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.

1992

SCD-HeFT

ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.

2005

SGLT2

Abstract Although the beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in heart failure (HF) have been well established, it is unknown whether SGLT2 inhibition confers benefit i

2026

SHIFT

Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.

2010

SOLVD

Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.

1991

STRONG-HF

High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.

2022

TOPCAT

Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.

2014

Val-HeFT

Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.

2001

VALOR-HCM

Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.

2022

VICTORIA

Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.

2020

Hypertension

14 trials

ACCOMPLISH

Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.

2008

ACCORD-BP

Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.

2010

ALLHAT

First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.

2002

ASCOT-BPLA

Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.

2005

HOPE-3

Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.

2016

HYVET

Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.

2008

INVEST

Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.

2003

LIFE

Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.

2002

PATHWAY-2

Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.

2015

RADIANCE-HTN

Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.

2018

SPRINT

Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.

2015

STEP

Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.

2021

SYMPLICITY

Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.

2014

VALUE

Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.

2004

Lipid Management

18 trials

4S Scandinavian

Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.

1994

AFCAPS

Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.

1998

AIM-HIGH

Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.

2011

CLEAR

Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.

2023

FOURIER

Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.

2017

HPS

Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.

2002

HPS2-THRIVE

Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.

2014

IMPROVE-IT

Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.

2015

ODYSSEY

Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.

2018

ORION-10

Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.

2020

ORION-11

Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.

2020

PROMINENT

Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.

2022

PROVE-IT

High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.

2004

REDUCE-IT

Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.

2019

REVEAL

Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.

2017

STRENGTH

Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.

2020

TNT

Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.

2005

WOSCOPS

Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.

1995

Atrial Fibrillation

19 trials

ACTIVE-A

Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.

2009

ACTIVE-W

Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.

2006

AFFIRM

Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.

2002

ARISTOTLE

Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.

2011

ATHENA

Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.

2009

ATLAS

Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.

2012

AVERROES

Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.

2011

CABANA

Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).

2019

CASTLE-AF

Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.

2018

EARLY-AF

Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.

2021

EAST-AFNET

Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.

2020

PFA-SHAM

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.

2026

PRAGUE-17

LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.

2020

PREVAIL

Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.

2014

PROTECT-AF

Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.

2009

RACE

Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.

2002

RE-LY

Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.

2009

ROCKET-AF

Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.

2011

STOP-AF

Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.

2021

Coronary Artery Disease

42 trials

BARI

Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.

2009

CANTOS

Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.

2017

COLCOT

Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.

2019

COMPASS

Low-dose rivaroxaban + aspirin vs aspirin alone in stable CAD/PAD — reduced major CV events.

2017

COMPLETE

Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.

2019

COURAGE

PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.

2007

CULPRIT-SHOCK

Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.

2017

DANAMI-3

FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.

2015

DAPA-MI

Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.

2023

ECLS-SHOCK

VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.

2023

EMPACT-MI

Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.

2024

EXCEL

PCI vs CABG in left main CAD — similar 5-year composite outcomes; controversial 10-year mortality signal.

2016

FAME

FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.

2009

FAME

FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.

2012

FREEDOM

CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.

2012

GUSTO-I

Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.

1993

HOST-EXAM

Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.

2021

IABP-SHOCK

IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.

2012

ISAR-REACT

Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.

2019

ISCHEMIA

Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.

2020

ISCHEMIA-CKD

Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.

2020

ISIS-2

Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.

1988

LoDoCo2

Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.

2020

MASTER-DAPT

1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.

2021

MATRIX

Radial vs femoral access and bivalirudin vs heparin in ACS — radial reduced major bleeding and net adverse events.

2015

MINT

BACKGROUND: The optimal transfusion strategy in patients with acute myocardial infarction (AMI) and anemia may be influenced by sex differences in pathophysiology and cardiovascular outcomes.

NOBLE

PCI vs CABG in left main CAD — CABG superior on composite endpoint.

2016

ONTARGET

Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.

2008

ORBITA

PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.

2017

ORBITA-2

PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.

2023

PEGASUS-TIMI

Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.

2015

PLATO

Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.

2009

RITA-3

Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.

2002

RIVAL

Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.

2011

SHOCK

Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.

1999

STICH

CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — long-term mortality benefit with CABG.

2011

STOPDAPT-2

1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.

2019

SYNTAX

PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.

2009

TIMACS

Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.

2009

TIMI

Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.

1999

TRITON-TIMI

Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.

2007

TWILIGHT

Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.

2019

Valvular Heart Disease

14 trials

AVATAR

Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.

2021

COAPT

MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.

2018

EARLY-TAVR

Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.

2024

EVERESTII

MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.

2011

Evolut

Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.

2019

MITRA-FR

MitraClip + medical therapy vs medical therapy alone in HF with secondary MR — no benefit (contrast COAPT).

2018

MITRA-HR

MitraClip plus medical therapy vs medical alone in secondary MR — outcomes differed between COAPT and MITRA-FR cohorts.

2018

NOTION-3

Impact of Angina on Outcome After Percutaneous Coronary Intervention in Patients Undergoing Transcatheter Aortic Valve Implantation: Insights From the NOTION-3 Trial

2026

PARTNER

TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.

2011

PARTNER

TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.

2016

PARTNER

TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.

2019

RECOVERY

Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.

2020

SURTAVI

Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.

2017

TRILUMINATE

Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.

2023

Perioperative & Antithrombotic

11 trials

Cardiac Arrhythmia

5 trials

Diabetes & Cardiometabolic

55 trials

ACCORD

Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.

2008

ACCORD-Lipid

Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.

2010

ACCORD-MIND

Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.

2011

ACHIEVE-1

Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.

2025

ACHIEVE-2

Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 tri

2026

ADVANCE

Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.

2008

AMPLITUDE-O

Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.

2021

ATTAIN-MAINTAIN

Abstract Incretins have improved the management of obesity and its related complications, but maintaining these health benefits requires ongoing administration, which can be challenging.

2026

CANTATA-SU

Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.

2013

CANVAS

Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.

2017

CARMELINA

Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.

2019

CAROLINA

Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.

2019

CREDENCE

Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.

2019

DAPA-CKD

Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.

2020

DECLARE-TIMI

Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.

2018

DELIVER

Placeholder twin endocrine entries — see SURPASS series for additional tirzepatide outcomes.

2024

DEVOTE

Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.

2017

DPP

Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.

2002

ELIXA

Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.

2015

EMPA-REG

Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.

2015

EMPULSE

Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.

2022

EXAMINE

Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.

2013

FIELD

Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.

2005

FLOW

Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.

2024

GRADE

Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.

2022

HARMONY

Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.

2018

LEADER

Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.

2016

Look

Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.

2012

LookAHEAD

Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.

2013

MERIT

BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.

2013

OASIS-1

Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.

2023

ORIGIN

Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.

2012

PIONEER-6

Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.

2019

REIMAGINE

Cagrilintide–semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study

2026

REWIND

Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.

2019

REWIND-CKD

AWARD-7: dulaglutide preserved eGFR and reduced albuminuria in T2D with moderate to severe CKD.

2018

SAVOR-TIMI

Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.

2013

SCALE

Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.

2015

SELECT

Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.

2023

SELECT-CKD

Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.

2024

STEP

Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.

2021

STEP

Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.

2022

STEP-HFpEF

Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.

2023

STEP-HFpEF

Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.

2024

SURMOUNT-1

Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.

2022

SURMOUNT-2

Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.

2023

SURMOUNT-MAINTAIN

Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial

2026

SURPASS-2

Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.

2021

SURPASS-3

Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.

2021

SURPASS-4

Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.

2021

SUSTAIN-6

Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.

2016

TECOS

Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.

2015

UKPDS

Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.

1998

VADT

Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.

2009

VERIFY

Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.

2019

Stroke & Acute Neurology

44 trials

AcT

Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.

2022

ANNEXA-4

Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.

2019

ATACH-II

Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.

2016

ATTRACTION

Efficacy and safety of tirofiban after successful endovascular reperfusion in acute ischaemic stroke (ATTRACTION) in China: a multicentre, double-blind, randomised controlled trial

2026

CENTAUR

AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.

2020

CHANCE

Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.

2013

CLARITY

Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

CLARITY-AD

Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.

2022

CRYSTAL-AF

Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.

2014

DAWN

Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.

2017

DEFUSE-2

Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.

2012

DEFUSE-3

Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.

2018

ECASS-3

IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.

2008

EMERGE

EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.

2022

EMPOWER

MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.

2017

ENCHANTED

Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.

2016

ESCAPE

Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.

2015

EVOLVE-1

Fremanezumab anti-CGRP antibody reduced migraine days in episodic and chronic migraine prevention.

2018

EXTEND

IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.

2019

EXTEND-IA

Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.

2015

FREEDOMS

Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

INTERACT2

Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.

2013

IST-3

IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.

2012

MR CLEAN

Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.

2015

NINDS

IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.

1995

OPERA-1

Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.

2017

ORATORIO

Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.

2017

PHOENIX

Phase 3 PHOENIX trial showed AMX0035 did not slow ALS progression vs placebo; product was withdrawn.

2024

POINT

Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.

2018

PROMISE-2

IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.

2020

RESILIENT

Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.

2020

REVASCAT

Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.

2015

SANAD

SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.

2007

SOCRATES

Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.

2016

SPS3

Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.

2012

STRIVE

Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.

2017

SUNBEAM

Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.

2019

SWIFT-PRIME

Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.

2015

THALES

Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.

2020

THRACE

Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.

2016

TIMELESS

Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.

2024

TRAILBLAZER-ALZ

Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.

2023

VALOR

Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.

2022

WAKE-UP

IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.

2018

COVID-19 & Vaccines

48 trials

ACTIV-2

COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.

2021

ACTIV-3

Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.

2021

ACTT-1

Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.

2020

ACTT-2

Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.

2021

ASTRAL-1

Sofosbuvir-velpatasvir achieved high SVR12 across HCV genotypes 1-6, establishing pan-genotypic therapy.

2015

BNT162b2

Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.

2020

C-EDGE

Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.

2015

CAPiTA

PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.

2015

ChAdOx1

ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.

2021

COV-BARRIER

Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.

2021

COVACTA

Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.

2021

DISCOVER

F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.

2020

EMPACTA

Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.

2021

ENSEMBLE

Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.

2021

EPIC-HR

Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.

2022

FLU-IVIG

Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.

2019

GISAID

Opposites Attract: no linked HIV transmissions among MSM serodiscordant couples when HIV-positive partner virally suppressed.

2018

HALO-Influenza

High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.

2014

HPTN-052

Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.

2011

HPTN-083

Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.

2021

ION-1

Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.

2014

iPrEx

Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.

2010

MATISSE

Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.

2023

MELODY

Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.

2022

MERINO

Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.

2018

MOVe-OUT

Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.

2022

mRNA-1273

Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.

2020

Nix-TB

BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.

2020

NVX-CoV2373

Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.

2021

OFLOTUB

Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.

2014

PANORAMIC

Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.

2022

PNEUMOSIL

PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to PCV13 for IgG responses in infants.

2020

PURPOSE-1

Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.

2024

PURPOSE-2

Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.

2024

R21

R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.

2023

RECOVERY

Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.

2021

REMAP-CAP

Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.

2021

REMoxTB

4-month moxifloxacin-containing regimens were non-inferior to standard 6-month therapy for drug-susceptible TB only weakly.

2014

RENOIR

Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.

2023

RTS,S

RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.

2015

SMART

Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.

2006

STAND

Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.

2021

START

Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.

2015

STOP-TB

TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.

2011

STREAM

9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.

2019

TEMPRANO

Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.

2015

WHO

WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.

2020

ZOE-50

Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.

2016

Oncology

106 trials

ADAURA

Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.

2020

ALCYONE

Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.

2018

ALEX

Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.

2017

APHINITY

Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.

2017

ARASENS

Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.

2022

ASCENT

Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.

2021

AURA3

Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.

2017

CALGB

Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.

2017

CARTITUDE-1

Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.

2021

CARTITUDE-4

Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.

2023

CASTOR

Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.

2016

CheckMate-067

Nivolumab + ipilimumab vs monotherapy in advanced melanoma — durable long-term OS benefit with combination.

2015

CheckMate-067

Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.

2017

CheckMate-214

Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.

2018

CheckMate-577

Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.

2021

CheckMate-649

Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.

2021

CheckMate-816

Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.

2022

CHOP

Tafasitamab plus lenalidomide and R-CHOP versus R-CHOP for first-line treatment of patients with high-risk diffuse large B-cell lymphoma (frontMIND): a global, phase 3, randomised, double-blind, place

2026

CLEAR

Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.

2021

CLEOPATRA

Pertuzumab + trastuzumab + docetaxel in HER2+ metastatic breast cancer — major overall survival benefit.

2012

CodeBreaK

Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.

2021

COMBI-AD

Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.

2017

COMPPARE

LBA5012 Background: There is a critical evidence gap on the relative benefits and harms of proton therapy (PT) compared with photon-based intensity-modulated radiation therapy (IMRT) in prostate cance

2026

CROSS

Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.

2012

CROWN

Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.

2020

DESTINY-Breast03

Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.

2022

DESTINY-Breast04

T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.

2022

ECHELON-1

Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.

2018

EMBRACA

Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.

2018

EMILIA

T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.

2012

EPCORE

Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.

2023

EV-302

Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.

2023

FLAURA

First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — PFS and OS benefit.

2017

FLAURA2

Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.

2023

GLP-1

10559 Background: Lung cancer (LC) is the leading cause of cancer-related mortality in the United States.

2026

HER2

39 Background: The benefit of adjuvant chemotherapy in premenopausal women with hormone receptor (HR)–positive, HER2-negative early breast cancer remains controversial.

2026

HER2

PURPOSE Clinical data for first-line combination of antibody-drug conjugates (ADC) and immune checkpoint inhibitors in human epidermal growth factor receptor 2 (HER2)–overexpressing advanced gastric o

2026

HER2CLIMB

Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.

2020

IDEA

IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.

2018

III

PURPOSE To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invas

IMbrave150

Atezolizumab plus bevacizumab improved OS and PFS vs sorafenib in unresectable hepatocellular carcinoma.

2020

IMpassion130

Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).

2018

IMpower010

Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.

2021

JCOG1008

The interim analysis of JCOG1008 demonstrated that chemoradiotherapy with cisplatin 40 mg/m 2 once a week for seven cycles (weekly cisplatin) was noninferior in terms of overall survival (OS) compared

2022

KarMMa

Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.

2021

KATHERINE

T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.

2019

KEYNOTE-024

First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.

2016

KEYNOTE-054

Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.

2018

KEYNOTE-189

First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.

2018

KEYNOTE-407

First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.

2018

KEYNOTE-426

Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.

2019

KEYNOTE-522

Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.

2020

KEYNOTE-590

Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.

2021

KEYNOTE-826

Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.

2021

KRYSTAL-1

Adagrasib produced responses in KRAS G12C-mutated NSCLC and colorectal cancer.

2022

LATITUDE

Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.

2017

MAGIC

Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.

2006

MAGNITUDE

Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.

2022

MAIA

Daratumumab plus Rd improved PFS and OS in transplant-ineligible newly diagnosed multiple myeloma.

2019

MajesTEC-1

Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.

2022

MALDI-TOF

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited.

MARIPOSA

Amivantamab plus lazertinib improved PFS vs osimertinib in first-line EGFR-mutated advanced NSCLC.

2023

MINDACT

MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.

2016

MONALEESA-2

Ribociclib plus letrozole improved PFS and OS in postmenopausal HR+/HER2- advanced breast cancer.

2016

monarchE

Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.

2020

MOSAIC

Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.

2004

NAPOLI-3

NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.

2023

NEMIO

PURPOSE To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab ± tremelimumab in patients with muscle-inv

2026

NETTER-1

177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.

2017

NOAH

Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.

2010

NOVA

Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.

2016

OlympiA

One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.

2021

PACIFIC

Durvalumab consolidation after chemoradiation in stage III NSCLC — major PFS and OS benefit.

2017

PACIFIC-2

Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.

2024

PALOMA-2

Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.

2016

PALOMA-3

Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.

2015

PAOLA-1

Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.

2019

PATHFINDER

LBA10509 Background: The MCED test (Galleri) detects a shared cancer signal from cell-free DNA in blood and predicts a cancer signal origin (CSO) to guide diagnostic (dx) workup.

2026

POLARIX

Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.

2022

POSEIDON

Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.

2022

PRADA

Letter by Jiang et al Regarding Article, “Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial”

2026

PRIMA

Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.

2019

PRODIGE

Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.

2021

PROfound

Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.

2020

PROFOUND

10541 Background: Early cancer detection reduces morbidity and mortality, but current recommended screening in China misses many lethal cancers.

2026

RAPIDO

Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.

2020

RELATIVITY-047

Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.

2022

RUBY

Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.

2023

RxPONDER

Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.

2021

SEZ6

Abstract Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms.

2026

SOLO-1

Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.

2018

STAMPEDE

Multi-arm trial showing docetaxel and abiraterone added to ADT improved survival in metastatic hormone-sensitive prostate cancer.

2017

SUCCESSOR-2

Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled tr

2026

TAILORx

Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.

2018

TITAN

Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.

2019

TOPAZ-1

Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.

2022

TOURMALINE-MM1

Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.

2016

TRACE

102 Background: Gastric cancer, a leading global malignancy with high incidence and mortality, poses a significant public health burden in China.

2026

TROPiCS-02

Sacituzumab govitecan improved PFS and OS in pretreated HR+/HER2- metastatic breast cancer.

2022

TROPION-Lung01

Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.

2023

TXI

10582 Background: Colonoscopy remains the gold standard for preventing colorectal cancer;

2026

WGS

202 Background: Ovarian cancer, including fallopian tube and primary peritoneal carcinoma, is often diagnosed at advanced stages.

2026

WSG

PURPOSE The WSG TP-II trial (ClinicalTrials.gov identifier: NCT03272477 ) was designed to compare the impact of 12 weeks of neoadjuvant trastuzumab + pertuzumab combined with endocrine therapy (ET) ve

X-ACT

Adjuvant capecitabine non-inferior to 5-FU/LV in stage III colon cancer with better tolerability.

2005

ZUMA-1

Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.

2017

ZUMA-7

Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.

2022

Critical Care

33 trials

65 trial

Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.

2020

6S hydroxyethyl

Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.

2012

ADRENAL

Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.

2018

ANDROMEDA-SHOCK

Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.

2019

APROCCHSS

Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.

2018

ARDSnet

Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.

2000

ARISE

Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.

2014

ART

Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.

2017

BaSICS

Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.

2021

CESAR

ECMO referral in severe respiratory failure — improved 6-month outcomes.

2009

CHEST

Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.

2012

CORTICUS

Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.

2008

CRASH-2

Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.

2010

CRASH-3

Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.

2019

EOLIA

Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.

2018

EPaNIC

Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.

2011

NICE-SUGAR

Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.

2009

PEPTIC

Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.

2020

PLUS

Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.

2022

ProCESS

Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.

2014

ProMISe

EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.

2015

PROSEVA

Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).

2013

ROSC

BACKGROUND: Exhaled end-tidal carbon dioxide (EtCO 2 ) trajectory is associated with out-of-hospital cardiac arrest (OHCA) outcomes.

2026

ROSE

Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.

2019

SAFE

4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.

2004

SALT-ED

Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.

2018

SNAP

Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority r

2026

SOAP-II

Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.

2010

SUP-ICU

Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.

2018

TARGET

Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.

2018

TRICC

Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.

1999

TRISS

Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.

2014

VASST

Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.

2008

Pulmonary Disease

28 trials

AMBITION

Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.

2015

ASCEND

Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.

2014

BOREAS

Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).

2023

CAPACITY

Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.

2011

CHEST-1

Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.

2013

DREAM

Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.

2012

ETHOS

Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.

2020

FLAME

LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.

2016

GRIPHON

Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.

2015

IMPACT

Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.

2018

INBUILD

Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.

2019

INPULSIS-1

Nintedanib in IPF — slowed FVC decline.

2014

INPULSIS-2

Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.

2014

LIBERTY

Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.

2022

MENSA

Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.

2014

NAVIGATOR

Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.

2021

NOTUS

NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.

2024

PATENT-1

Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.

2013

POET-COPD

Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.

2011

QUEST

Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.

2018

SENSCIS

Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.

2019

SERAPHIN

Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.

2013

SIRIUS

Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.

2014

STELLAR

Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.

2023

TORCH

Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.

2007

TRIBUTE

Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.

2018

UPLIFT

Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.

2008

WISDOM

Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.

2014

Women’s Health

6 trials

Obstetrics

17 trials

ALPS

Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.

2016

ARRIVE

Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.

2018

ASPRE

Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.

2017

BEAM

Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.

2008

C*STAR

Pooled cerclage data informed practice for short cervix; ultrasound-indicated cerclage reduced preterm birth in selected.

2018

CHAP

Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.

2022

CHIPS

Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.

2015

FlamingoTRA

PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.

2019

GBS3

GBS3: routine antenatal screening vs risk-based did not significantly reduce early-onset neonatal GBS disease.

2024

HAPO

HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.

2008

MAGPIE

Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.

2002

MFMU

17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.

2003

MOMS

Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.

2011

PRISM

Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.

2019

STRIDER

Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.

2018

Term

Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.

2000

WOMAN

Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.

2017

Primary Prevention

32 trials

ALLHAT-LLT

Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.

2002

ASPREE

Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.

2018

COMPASS

Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.

2017

D2d

Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.

2019

DASH

DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.

1997

DASH-Sodium

Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.

2001

DCCT

Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.

1993

EAGLES

Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.

2016

HOPE

Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.

2000

MEGA

Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.

2006

MILES

NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.

2011

NELSON

Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.

2020

NORDICC

Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.

2022

PLCO

PLCO: PSA screening did not reduce prostate cancer mortality; annual CXR did not reduce lung cancer mortality.

2012

PolyIran

Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.

2019

PREDIMED

Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.

2013

PREDIMED-Plus

Energy-reduced Mediterranean diet plus physical activity reduced visceral adiposity and possibly CV outcomes.

2023

PROSPER

Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.

2002

PROVE-HF

TAME PAD: TAILORed prevention efforts in peripheral arterial disease; multidisciplinary intervention outcomes mixed.

2023

PURE

PURE study: high carbohydrate intake associated with higher mortality; total fat with lower mortality globally.

2017

SALT

SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.

2021

SHEP

Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.

1991

SPRINT-MIND

Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.

2019

STAREE

STAREE will assess atorvastatin in older adults for disability-free survival; reflects elderly statin question.

2025

TIPS

TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.

2021

TONE

Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.

1998

VITAL

Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.

2019

VITAL-Bone

Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.

2022

VITAL-DEP

Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.

2020

VITAL-Rhythm

Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.

2020

WHI

Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.

2006

WHISH

Multiple women's health prevention trials informed lifestyle guidance; activity recommendations widely cited.

2017

Cardiology

164 trials

4S Scandinavian

Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.

1994

A-HeFT

Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.

2004

AC01

Safety, pharmacokinetics, and exploratory efficacy of the oral ghrelin receptor agonist AC01 in heart failure with reduced ejection fraction (GOAL-HF1): a randomised, double-blind, placebo-controlled,

2026

ACCOMPLISH

Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.

2008

ACCORD-BP

Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.

2010

ACTIVE-A

Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.

2009

ACTIVE-W

Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.

2006

AFCAPS

Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.

1998

AFFIRM

Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.

2002

AIM-HIGH

Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.

2011

AIRE

Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.

1993

ALLHAT

First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.

2002

ARISTOTLE

Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.

2011

ASCOT-BPLA

Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.

2005

ATHENA

Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.

2009

ATLAS

Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.

2012

ATTR-ACT

Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.

2018

AUGUSTUS

Antithrombotic strategies in AF + ACS/PCI — apixaban without aspirin reduced bleeding without raising ischemic events.

2019

AVATAR

Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.

2021

AVERROES

Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.

2011

BARI

Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.

2009

BRIDGE

Bridging anticoagulation vs no bridging during warfarin interruption in AF — no thromboembolism reduction, more bleeding.

2015

CABANA

Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).

2019

CANTOS

Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.

2017

CARE-HF

CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.

2005

CAST

Encainide/flecainide vs placebo to suppress PVCs post-MI — increased mortality; pivotal negative trial.

1991

CASTLE-AF

Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.

2018

CHAMPION

Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.

2011

CHARM-Added

Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.

2003

CHARM-Alternative

Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.

2003

CIBIS-II

Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.

1999

CLEAR

Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.

2023

COAPT

MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.

2018

COLCOT

Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.

2019

COMPANION

CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.

2004

COMPASS

Low-dose rivaroxaban + aspirin vs aspirin alone in stable CAD/PAD — reduced major CV events.

2017

COMPLETE

Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.

2019

CONSENSUS

Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.

1987

COPERNICUS

Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.

2001

COURAGE

PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.

2007

CULPRIT-SHOCK

Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.

2017

DANAMI-3

FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.

2015

DANISH

Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.

2016

DAPA

Letter by Qin et al Regarding Article “Dapagliflozin in Patients Hospitalized for Heart Failure: Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial and Meta-Analysis of Sodium-Glucos

2026

DAPA-HF

Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.

2019

DAPA-MI

Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.

2023

DELIVER

Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.

2022

EARLY-AF

Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.

2021

EARLY-TAVR

Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.

2024

EAST-AFNET

Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.

2020

ECLS-SHOCK

VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.

2023

EMPACT-MI

Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.

2024

EMPEROR-Preserved

Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.

2021

EMPEROR-Reduced

Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.

2020

EMPHASIS-HF

Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.

2011

ENTRUST-AF-PCI

Edoxaban-based dual therapy vs warfarin triple therapy after PCI in AF — non-inferior bleeding endpoint.

2019

EPHESUS

Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.

2003

EVERESTII

MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.

2011

Evolut

Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.

2019

EXCEL

PCI vs CABG in left main CAD — similar 5-year composite outcomes; controversial 10-year mortality signal.

2016

EXPLORER-HCM

Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.

2020

FAME

FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.

2009

FAME

FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.

2012

FINEARTS-HF

Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.

2024

FOURIER

Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.

2017

FREEDOM

CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.

2012

GALACTIC-HF

Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.

2021

GUSTO-I

Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.

1993

HOPE-3

Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.

2016

HOST-EXAM

Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.

2021

HPS

Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.

2002

HPS2-THRIVE

Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.

2014

HYVET

Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.

2008

I-PRESERVE

Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.

2008

IABP-SHOCK

IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.

2012

IMPROVE-IT

Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.

2015

INVEST

Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.

2003

ISAR-REACT

Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.

2019

ISCHEMIA

Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.

2020

ISCHEMIA-CKD

Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.

2020

ISIS-2

Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.

1988

LIFE

Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.

2002

LoDoCo2

Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.

2020

MADIT-CRT

CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.

2009

MADIT-II

Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.

2002

MADIT-RIT

High-rate or delayed ICD therapy vs conventional programming — reduced inappropriate shocks and mortality.

2012

MANAGE

Dabigatran in perioperative MI/myocardial injury after non-cardiac surgery — reduced major vascular complications.

2018

MASTER-DAPT

1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.

2021

MATRIX

Radial vs femoral access and bivalirudin vs heparin in ACS — radial reduced major bleeding and net adverse events.

2015

MERIT-HF

Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.

1999

MINT

BACKGROUND: The optimal transfusion strategy in patients with acute myocardial infarction (AMI) and anemia may be influenced by sex differences in pathophysiology and cardiovascular outcomes.

MITRA-FR

MitraClip + medical therapy vs medical therapy alone in HF with secondary MR — no benefit (contrast COAPT).

2018

MITRA-HR

MitraClip plus medical therapy vs medical alone in secondary MR — outcomes differed between COAPT and MITRA-FR cohorts.

2018

NOBLE

PCI vs CABG in left main CAD — CABG superior on composite endpoint.

2016

NOTION-3

Impact of Angina on Outcome After Percutaneous Coronary Intervention in Patients Undergoing Transcatheter Aortic Valve Implantation: Insights From the NOTION-3 Trial

2026

ODYSSEY

Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.

2018

ONTARGET

Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.

2008

OPTIC

Amiodarone + beta-blocker vs sotalol vs beta-blocker alone for ICD shock prevention — amiodarone combo most effective.

2006

ORBITA

PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.

2017

ORBITA-2

PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.

2023

ORION-10

Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.

2020

ORION-11

Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.

2020

PARADIGM-HF

Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.

2014

PARTITA

VT ablation after first appropriate ICD shock vs continued medical therapy — reduced death/VT storm.

2022

PARTNER

TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.

2011

PARTNER

TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.

2016

PARTNER

TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.

2019

PATHWAY-2

Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.

2015

PAUSE

Standardized DOAC interruption strategy in AF undergoing surgery — low rates of bleeding and thromboembolism.

2019

PEGASUS-TIMI

Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.

2015

PERIOP-2

LMWH bridging vs placebo during warfarin interruption in high-risk AF/mechanical valves — no benefit, more bleeding.

2021

PFA-SHAM

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.

2026

PIONEER-AF-PCI

Rivaroxaban-based vs warfarin triple therapy after PCI in AF — reduced clinically significant bleeding.

2016

PIONEER-HF

Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.

2019

PLATO

Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.

2009

POISE

Perioperative metoprolol in non-cardiac surgery — fewer MIs but more strokes and total deaths.

2008

POISE-2

Perioperative aspirin and clonidine in non-cardiac surgery — neither reduced CV events; aspirin increased bleeding.

2014

PRAGUE-17

LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.

2020

PREVAIL

Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.

2014

PROMINENT

Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.

2022

PROTECT-AF

Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.

2009

PROVE-IT

High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.

2004

RACE

Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.

2002

RADIANCE-HTN

Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.

2018

RAFT

CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.

2010

RALES

Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.

1999

RE-DUAL

Dabigatran + P2Y12 inhibitor vs warfarin triple therapy after PCI in AF — less bleeding, non-inferior thromboembolism.

2017

RE-LY

Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.

2009

RECOVERY

Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.

2020

REDUCE-IT

Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.

2019

REVEAL

Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.

2017

RITA-3

Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.

2002

RIVAL

Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.

2011

ROCKET-AF

Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.

2011

SAVE

Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.

1992

SCD-HeFT

ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.

2005

SGLT2

Abstract Although the beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in heart failure (HF) have been well established, it is unknown whether SGLT2 inhibition confers benefit i

2026

SHIFT

Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.

2010

SHOCK

Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.

1999

SOLVD

Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.

1991

SPRINT

Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.

2015

STEP

Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.

2021

STICH

CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — long-term mortality benefit with CABG.

2011

STOP-AF

Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.

2021

STOPDAPT-2

1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.

2019

STRENGTH

Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.

2020

STRONG-HF

High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.

2022

SURTAVI

Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.

2017

SYMPLICITY

Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.

2014

SYNTAX

PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.

2009

TIMACS

Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.

2009

TIMI

Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.

1999

TNT

Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.

2005

TOPCAT

Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.

2014

TRILUMINATE

Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.

2023

TRITON-TIMI

Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.

2007

TWILIGHT

Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.

2019

Val-HeFT

Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.

2001

VALOR-HCM

Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.

2022

VALUE

Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.

2004

VANISH

Catheter ablation vs escalated antiarrhythmic therapy in recurrent VT — reduced composite of death/VT storm/ICD shocks.

2016

VICTORIA

Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.

2020

WOEST

Warfarin + clopidogrel vs triple therapy after PCI in patients on OAC — reduced bleeding without ischemic penalty.

2013

WOSCOPS

Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.

1995

Endocrinology

55 trials

ACCORD

Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.

2008

ACCORD-Lipid

Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.

2010

ACCORD-MIND

Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.

2011

ACHIEVE-1

Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.

2025

ACHIEVE-2

Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 tri

2026

ADVANCE

Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.

2008

AMPLITUDE-O

Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.

2021

ATTAIN-MAINTAIN

Abstract Incretins have improved the management of obesity and its related complications, but maintaining these health benefits requires ongoing administration, which can be challenging.

2026

CANTATA-SU

Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.

2013

CANVAS

Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.

2017

CARMELINA

Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.

2019

CAROLINA

Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.

2019

CREDENCE

Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.

2019

DAPA-CKD

Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.

2020

DECLARE-TIMI

Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.

2018

DELIVER

Placeholder twin endocrine entries — see SURPASS series for additional tirzepatide outcomes.

2024

DEVOTE

Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.

2017

DPP

Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.

2002

ELIXA

Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.

2015

EMPA-REG

Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.

2015

EMPULSE

Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.

2022

EXAMINE

Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.

2013

FIELD

Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.

2005

FLOW

Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.

2024

GRADE

Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.

2022

HARMONY

Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.

2018

LEADER

Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.

2016

Look

Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.

2012

LookAHEAD

Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.

2013

MERIT

BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.

2013

OASIS-1

Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.

2023

ORIGIN

Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.

2012

PIONEER-6

Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.

2019

REIMAGINE

Cagrilintide–semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study

2026

REWIND

Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.

2019

REWIND-CKD

AWARD-7: dulaglutide preserved eGFR and reduced albuminuria in T2D with moderate to severe CKD.

2018

SAVOR-TIMI

Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.

2013

SCALE

Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.

2015

SELECT

Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.

2023

SELECT-CKD

Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.

2024

STEP

Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.

2021

STEP

Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.

2022

STEP-HFpEF

Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.

2023

STEP-HFpEF

Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.

2024

SURMOUNT-1

Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.

2022

SURMOUNT-2

Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.

2023

SURMOUNT-MAINTAIN

Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial

2026

SURPASS-2

Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.

2021

SURPASS-3

Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.

2021

SURPASS-4

Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.

2021

SUSTAIN-6

Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.

2016

TECOS

Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.

2015

UKPDS

Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.

1998

VADT

Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.

2009

VERIFY

Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.

2019

Neurology

44 trials

AcT

Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.

2022

ANNEXA-4

Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.

2019

ATACH-II

Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.

2016

ATTRACTION

Efficacy and safety of tirofiban after successful endovascular reperfusion in acute ischaemic stroke (ATTRACTION) in China: a multicentre, double-blind, randomised controlled trial

2026

CENTAUR

AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.

2020

CHANCE

Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.

2013

CLARITY

Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

CLARITY-AD

Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.

2022

CRYSTAL-AF

Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.

2014

DAWN

Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.

2017

DEFUSE-2

Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.

2012

DEFUSE-3

Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.

2018

ECASS-3

IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.

2008

EMERGE

EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.

2022

EMPOWER

MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.

2017

ENCHANTED

Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.

2016

ESCAPE

Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.

2015

EVOLVE-1

Fremanezumab anti-CGRP antibody reduced migraine days in episodic and chronic migraine prevention.

2018

EXTEND

IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.

2019

EXTEND-IA

Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.

2015

FREEDOMS

Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

INTERACT2

Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.

2013

IST-3

IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.

2012

MR CLEAN

Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.

2015

NINDS

IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.

1995

OPERA-1

Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.

2017

ORATORIO

Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.

2017

PHOENIX

Phase 3 PHOENIX trial showed AMX0035 did not slow ALS progression vs placebo; product was withdrawn.

2024

POINT

Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.

2018

PROMISE-2

IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.

2020

RESILIENT

Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.

2020

REVASCAT

Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.

2015

SANAD

SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.

2007

SOCRATES

Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.

2016

SPS3

Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.

2012

STRIVE

Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.

2017

SUNBEAM

Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.

2019

SWIFT-PRIME

Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.

2015

THALES

Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.

2020

THRACE

Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.

2016

TIMELESS

Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.

2024

TRAILBLAZER-ALZ

Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.

2023

VALOR

Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.

2022

WAKE-UP

IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.

2018

Pulmonology

28 trials

AMBITION

Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.

2015

ASCEND

Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.

2014

BOREAS

Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).

2023

CAPACITY

Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.

2011

CHEST-1

Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.

2013

DREAM

Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.

2012

ETHOS

Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.

2020

FLAME

LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.

2016

GRIPHON

Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.

2015

IMPACT

Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.

2018

INBUILD

Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.

2019

INPULSIS-1

Nintedanib in IPF — slowed FVC decline.

2014

INPULSIS-2

Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.

2014

LIBERTY

Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.

2022

MENSA

Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.

2014

NAVIGATOR

Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.

2021

NOTUS

NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.

2024

PATENT-1

Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.

2013

POET-COPD

Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.

2011

QUEST

Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.

2018

SENSCIS

Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.

2019

SERAPHIN

Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.

2013

SIRIUS

Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.

2014

STELLAR

Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.

2023

TORCH

Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.

2007

TRIBUTE

Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.

2018

UPLIFT

Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.

2008

WISDOM

Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.

2014

Critical Care

33 trials

65 trial

Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.

2020

6S hydroxyethyl

Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.

2012

ADRENAL

Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.

2018

ANDROMEDA-SHOCK

Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.

2019

APROCCHSS

Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.

2018

ARDSnet

Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.

2000

ARISE

Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.

2014

ART

Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.

2017

BaSICS

Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.

2021

CESAR

ECMO referral in severe respiratory failure — improved 6-month outcomes.

2009

CHEST

Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.

2012

CORTICUS

Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.

2008

CRASH-2

Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.

2010

CRASH-3

Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.

2019

EOLIA

Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.

2018

EPaNIC

Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.

2011

NICE-SUGAR

Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.

2009

PEPTIC

Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.

2020

PLUS

Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.

2022

ProCESS

Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.

2014

ProMISe

EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.

2015

PROSEVA

Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).

2013

ROSC

BACKGROUND: Exhaled end-tidal carbon dioxide (EtCO 2 ) trajectory is associated with out-of-hospital cardiac arrest (OHCA) outcomes.

2026

ROSE

Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.

2019

SAFE

4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.

2004

SALT-ED

Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.

2018

SNAP

Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority r

2026

SOAP-II

Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.

2010

SUP-ICU

Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.

2018

TARGET

Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.

2018

TRICC

Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.

1999

TRISS

Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.

2014

VASST

Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.

2008

Oncology

106 trials

ADAURA

Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.

2020

ALCYONE

Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.

2018

ALEX

Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.

2017

APHINITY

Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.

2017

ARASENS

Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.

2022

ASCENT

Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.

2021

AURA3

Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.

2017

CALGB

Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.

2017

CARTITUDE-1

Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.

2021

CARTITUDE-4

Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.

2023

CASTOR

Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.

2016

CheckMate-067

Nivolumab + ipilimumab vs monotherapy in advanced melanoma — durable long-term OS benefit with combination.

2015

CheckMate-067

Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.

2017

CheckMate-214

Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.

2018

CheckMate-577

Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.

2021

CheckMate-649

Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.

2021

CheckMate-816

Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.

2022

CHOP

Tafasitamab plus lenalidomide and R-CHOP versus R-CHOP for first-line treatment of patients with high-risk diffuse large B-cell lymphoma (frontMIND): a global, phase 3, randomised, double-blind, place

2026

CLEAR

Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.

2021

CLEOPATRA

Pertuzumab + trastuzumab + docetaxel in HER2+ metastatic breast cancer — major overall survival benefit.

2012

CodeBreaK

Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.

2021

COMBI-AD

Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.

2017

COMPPARE

LBA5012 Background: There is a critical evidence gap on the relative benefits and harms of proton therapy (PT) compared with photon-based intensity-modulated radiation therapy (IMRT) in prostate cance

2026

CROSS

Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.

2012

CROWN

Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.

2020

DESTINY-Breast03

Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.

2022

DESTINY-Breast04

T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.

2022

ECHELON-1

Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.

2018

EMBRACA

Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.

2018

EMILIA

T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.

2012

EPCORE

Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.

2023

EV-302

Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.

2023

FLAURA

First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — PFS and OS benefit.

2017

FLAURA2

Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.

2023

GLP-1

10559 Background: Lung cancer (LC) is the leading cause of cancer-related mortality in the United States.

2026

HER2

39 Background: The benefit of adjuvant chemotherapy in premenopausal women with hormone receptor (HR)–positive, HER2-negative early breast cancer remains controversial.

2026

HER2

PURPOSE Clinical data for first-line combination of antibody-drug conjugates (ADC) and immune checkpoint inhibitors in human epidermal growth factor receptor 2 (HER2)–overexpressing advanced gastric o

2026

HER2CLIMB

Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.

2020

IDEA

IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.

2018

III

PURPOSE To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invas

IMbrave150

Atezolizumab plus bevacizumab improved OS and PFS vs sorafenib in unresectable hepatocellular carcinoma.

2020

IMpassion130

Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).

2018

IMpower010

Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.

2021

JCOG1008

The interim analysis of JCOG1008 demonstrated that chemoradiotherapy with cisplatin 40 mg/m 2 once a week for seven cycles (weekly cisplatin) was noninferior in terms of overall survival (OS) compared

2022

KarMMa

Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.

2021

KATHERINE

T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.

2019

KEYNOTE-024

First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.

2016

KEYNOTE-054

Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.

2018

KEYNOTE-189

First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.

2018

KEYNOTE-407

First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.

2018

KEYNOTE-426

Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.

2019

KEYNOTE-522

Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.

2020

KEYNOTE-590

Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.

2021

KEYNOTE-826

Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.

2021

KRYSTAL-1

Adagrasib produced responses in KRAS G12C-mutated NSCLC and colorectal cancer.

2022

LATITUDE

Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.

2017

MAGIC

Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.

2006

MAGNITUDE

Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.

2022

MAIA

Daratumumab plus Rd improved PFS and OS in transplant-ineligible newly diagnosed multiple myeloma.

2019

MajesTEC-1

Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.

2022

MALDI-TOF

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited.

MARIPOSA

Amivantamab plus lazertinib improved PFS vs osimertinib in first-line EGFR-mutated advanced NSCLC.

2023

MINDACT

MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.

2016

MONALEESA-2

Ribociclib plus letrozole improved PFS and OS in postmenopausal HR+/HER2- advanced breast cancer.

2016

monarchE

Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.

2020

MOSAIC

Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.

2004

NAPOLI-3

NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.

2023

NEMIO

PURPOSE To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab ± tremelimumab in patients with muscle-inv

2026

NETTER-1

177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.

2017

NOAH

Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.

2010

NOVA

Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.

2016

OlympiA

One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.

2021

PACIFIC

Durvalumab consolidation after chemoradiation in stage III NSCLC — major PFS and OS benefit.

2017

PACIFIC-2

Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.

2024

PALOMA-2

Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.

2016

PALOMA-3

Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.

2015

PAOLA-1

Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.

2019

PATHFINDER

LBA10509 Background: The MCED test (Galleri) detects a shared cancer signal from cell-free DNA in blood and predicts a cancer signal origin (CSO) to guide diagnostic (dx) workup.

2026

POLARIX

Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.

2022

POSEIDON

Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.

2022

PRADA

Letter by Jiang et al Regarding Article, “Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial”

2026

PRIMA

Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.

2019

PRODIGE

Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.

2021

PROfound

Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.

2020

PROFOUND

10541 Background: Early cancer detection reduces morbidity and mortality, but current recommended screening in China misses many lethal cancers.

2026

RAPIDO

Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.

2020

RELATIVITY-047

Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.

2022

RUBY

Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.

2023

RxPONDER

Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.

2021

SEZ6

Abstract Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms.

2026

SOLO-1

Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.

2018

STAMPEDE

Multi-arm trial showing docetaxel and abiraterone added to ADT improved survival in metastatic hormone-sensitive prostate cancer.

2017

SUCCESSOR-2

Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled tr

2026

TAILORx

Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.

2018

TITAN

Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.

2019

TOPAZ-1

Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.

2022

TOURMALINE-MM1

Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.

2016

TRACE

102 Background: Gastric cancer, a leading global malignancy with high incidence and mortality, poses a significant public health burden in China.

2026

TROPiCS-02

Sacituzumab govitecan improved PFS and OS in pretreated HR+/HER2- metastatic breast cancer.

2022

TROPION-Lung01

Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.

2023

TXI

10582 Background: Colonoscopy remains the gold standard for preventing colorectal cancer;

2026

WGS

202 Background: Ovarian cancer, including fallopian tube and primary peritoneal carcinoma, is often diagnosed at advanced stages.

2026

WSG

PURPOSE The WSG TP-II trial (ClinicalTrials.gov identifier: NCT03272477 ) was designed to compare the impact of 12 weeks of neoadjuvant trastuzumab + pertuzumab combined with endocrine therapy (ET) ve

X-ACT

Adjuvant capecitabine non-inferior to 5-FU/LV in stage III colon cancer with better tolerability.

2005

ZUMA-1

Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.

2017

ZUMA-7

Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.

2022

Infectious Disease

48 trials

ACTIV-2

COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.

2021

ACTIV-3

Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.

2021

ACTT-1

Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.

2020

ACTT-2

Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.

2021

ASTRAL-1

Sofosbuvir-velpatasvir achieved high SVR12 across HCV genotypes 1-6, establishing pan-genotypic therapy.

2015

BNT162b2

Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.

2020

C-EDGE

Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.

2015

CAPiTA

PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.

2015

ChAdOx1

ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.

2021

COV-BARRIER

Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.

2021

COVACTA

Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.

2021

DISCOVER

F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.

2020

EMPACTA

Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.

2021

ENSEMBLE

Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.

2021

EPIC-HR

Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.

2022

FLU-IVIG

Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.

2019

GISAID

Opposites Attract: no linked HIV transmissions among MSM serodiscordant couples when HIV-positive partner virally suppressed.

2018

HALO-Influenza

High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.

2014

HPTN-052

Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.

2011

HPTN-083

Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.

2021

ION-1

Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.

2014

iPrEx

Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.

2010

MATISSE

Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.

2023

MELODY

Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.

2022

MERINO

Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.

2018

MOVe-OUT

Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.

2022

mRNA-1273

Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.

2020

Nix-TB

BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.

2020

NVX-CoV2373

Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.

2021

OFLOTUB

Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.

2014

PANORAMIC

Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.

2022

PNEUMOSIL

PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to PCV13 for IgG responses in infants.

2020

PURPOSE-1

Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.

2024

PURPOSE-2

Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.

2024

R21

R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.

2023

RECOVERY

Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.

2021

REMAP-CAP

Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.

2021

REMoxTB

4-month moxifloxacin-containing regimens were non-inferior to standard 6-month therapy for drug-susceptible TB only weakly.

2014

RENOIR

Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.

2023

RTS,S

RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.

2015

SMART

Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.

2006

STAND

Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.

2021

START

Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.

2015

STOP-TB

TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.

2011

STREAM

9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.

2019

TEMPRANO

Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.

2015

WHO

WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.

2020

ZOE-50

Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.

2016

Women’s Health & OB-GYN

23 trials

ALPS

Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.

2016

ARRIVE

Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.

2018

ASPRE

Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.

2017

BEAM

Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.

2008

C*STAR

Pooled cerclage data informed practice for short cervix; ultrasound-indicated cerclage reduced preterm birth in selected.

2018

CD40

Efficacy and safety of the CD40 ligand inhibitor dapirolizumab pegol in systemic lupus erythematosus (PHOENYCS GO): a randomised, double-blind, placebo-controlled, phase 3 trial

2026

CHAP

Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.

2022

CHIPS

Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.

2015

FlamingoTRA

PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.

2019

GBS3

GBS3: routine antenatal screening vs risk-based did not significantly reduce early-onset neonatal GBS disease.

2024

HAPO

HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.

2008

HERS

Estrogen plus progestin did not reduce CHD events in women with established coronary heart disease.

1998

MAGPIE

Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.

2002

MFMU

17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.

2003

MOMS

Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.

2011

MsFLASH

Escitalopram modestly reduced frequency and severity of menopausal hot flashes vs placebo in non-hormonal trial.

2011

PRISM

Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.

2019

SKYLIGHT

Fezolinetant NK3 receptor antagonist reduced moderate-severe vasomotor symptoms in menopause vs placebo.

2023

STRIDER

Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.

2018

Term

Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.

2000

VICTORY

TMIST will compare digital breast tomosynthesis vs digital mammography for advanced breast cancer outcomes.

2025

WOMAN

Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.

2017

Women's

Hormone replacement (estrogen + progestin) in postmenopausal women — increased breast cancer and CVD; stopped early.

2002

General Medicine

32 trials

ALLHAT-LLT

Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.

2002

ASPREE

Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.

2018

COMPASS

Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.

2017

D2d

Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.

2019

DASH

DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.

1997

DASH-Sodium

Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.

2001

DCCT

Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.

1993

EAGLES

Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.

2016

HOPE

Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.

2000

MEGA

Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.

2006

MILES

NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.

2011

NELSON

Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.

2020

NORDICC

Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.

2022

PLCO

PLCO: PSA screening did not reduce prostate cancer mortality; annual CXR did not reduce lung cancer mortality.

2012

PolyIran

Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.

2019

PREDIMED

Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.

2013

PREDIMED-Plus

Energy-reduced Mediterranean diet plus physical activity reduced visceral adiposity and possibly CV outcomes.

2023

PROSPER

Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.

2002

PROVE-HF

TAME PAD: TAILORed prevention efforts in peripheral arterial disease; multidisciplinary intervention outcomes mixed.

2023

PURE

PURE study: high carbohydrate intake associated with higher mortality; total fat with lower mortality globally.

2017

SALT

SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.

2021

SHEP

Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.

1991

SPRINT-MIND

Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.

2019

STAREE

STAREE will assess atorvastatin in older adults for disability-free survival; reflects elderly statin question.

2025

TIPS

TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.

2021

TONE

Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.

1998

VITAL

Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.

2019

VITAL-Bone

Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.

2022

VITAL-DEP

Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.

2020

VITAL-Rhythm

Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.

2020

WHI

Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.

2006

WHISH

Multiple women's health prevention trials informed lifestyle guidance; activity recommendations widely cited.

2017

Last 24 hours

2 trials

Last 7 days

5 trials

Last 30 days

15 trials

SNAP

Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority r

2026

SUCCESSOR-2

Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled tr

2026

SGLT2

Abstract Although the beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in heart failure (HF) have been well established, it is unknown whether SGLT2 inhibition confers benefit i

2026

REIMAGINE

Cagrilintide–semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study

2026

ACHIEVE-2

Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 tri

2026

COMPPARE

LBA5012 Background: There is a critical evidence gap on the relative benefits and harms of proton therapy (PT) compared with photon-based intensity-modulated radiation therapy (IMRT) in prostate cance

2026

PATHFINDER

LBA10509 Background: The MCED test (Galleri) detects a shared cancer signal from cell-free DNA in blood and predicts a cancer signal origin (CSO) to guide diagnostic (dx) workup.

2026

DAPA

Letter by Qin et al Regarding Article “Dapagliflozin in Patients Hospitalized for Heart Failure: Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial and Meta-Analysis of Sodium-Glucos

2026

PRADA

Letter by Jiang et al Regarding Article, “Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial”

2026

SEZ6

Abstract Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms.

2026

CD40

Efficacy and safety of the CD40 ligand inhibitor dapirolizumab pegol in systemic lupus erythematosus (PHOENYCS GO): a randomised, double-blind, placebo-controlled, phase 3 trial

2026

CHOP

Tafasitamab plus lenalidomide and R-CHOP versus R-CHOP for first-line treatment of patients with high-risk diffuse large B-cell lymphoma (frontMIND): a global, phase 3, randomised, double-blind, place

2026

TXI

10582 Background: Colonoscopy remains the gold standard for preventing colorectal cancer;

2026

GLP-1

10559 Background: Lung cancer (LC) is the leading cause of cancer-related mortality in the United States.

2026

PROFOUND

10541 Background: Early cancer detection reduces morbidity and mortality, but current recommended screening in China misses many lethal cancers.

2026

Last year

511 trials

NEMIO

PURPOSE To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab ± tremelimumab in patients with muscle-inv

2026

PFA-SHAM

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.

2026

NOTION-3

Impact of Angina on Outcome After Percutaneous Coronary Intervention in Patients Undergoing Transcatheter Aortic Valve Implantation: Insights From the NOTION-3 Trial

2026

TRIBUTE

Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.

2018

III

PURPOSE To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invas

MALDI-TOF

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited.

GBS3

GBS3: routine antenatal screening vs risk-based did not significantly reduce early-onset neonatal GBS disease.

2024

VICTORY

TMIST will compare digital breast tomosynthesis vs digital mammography for advanced breast cancer outcomes.

2025

SKYLIGHT

Fezolinetant NK3 receptor antagonist reduced moderate-severe vasomotor symptoms in menopause vs placebo.

2023

MsFLASH

Escitalopram modestly reduced frequency and severity of menopausal hot flashes vs placebo in non-hormonal trial.

2011

HERS

Estrogen plus progestin did not reduce CHD events in women with established coronary heart disease.

1998

STRIDER

Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.

2018

BEAM

Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.

2008

MOMS

Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.

2011

Term

Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.

2000

PRISM

Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.

2019

MFMU

17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.

2003

FlamingoTRA

PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.

2019

PATENT-1

Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.

2013

STELLAR

Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.

2023

BOREAS

Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).

2023

INBUILD

Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.

2019

INPULSIS-2

Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.

2014

PEPTIC

Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.

2020

VITAL-DEP

Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.

2020

SURMOUNT-2

Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.

2023

C*STAR

Pooled cerclage data informed practice for short cervix; ultrasound-indicated cerclage reduced preterm birth in selected.

2018

HAPO

HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.

2008

WOMAN

Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.

2017

ASPRE

Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.

2017

CHAP

Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.

2022

CHIPS

Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.

2015

MAGPIE

Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.

2002

ALPS

Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.

2016

CHEST-1

Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.

2013

AMBITION

Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.

2015

GRIPHON

Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.

2015

SERAPHIN

Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.

2013

NOTUS

NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.

2024

LIBERTY

Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.

2022

QUEST

Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.

2018

NAVIGATOR

Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.

2021

SIRIUS

Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.

2014

MENSA

Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.

2014

DREAM

Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.

2012

SENSCIS

Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.

2019

POET-COPD

Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.

2011

WISDOM

Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.

2014

FLAME

LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.

2016

ETHOS

Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.

2020

IMPACT

Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.

2018

UPLIFT

Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.

2008

TORCH

Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.

2007

CRASH-3

Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.

2019

CRASH-2

Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.

2010

65 trial

Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.

2020

EPaNIC

Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.

2011

TARGET

Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.

2018

SUP-ICU

Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.

2018

NICE-SUGAR

Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.

2009

PLUS

Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.

2022

BaSICS

Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.

2021

SALT-ED

Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.

2018

CHEST

Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.

2012

6S hydroxyethyl

Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.

2012

SAFE

4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.

2004

EOLIA

Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.

2018

ROSE

Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.

2019

ART

Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.

2017

PROSEVA

Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).

2013

ProMISe

EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.

2015

ARISE

Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.

2014

SOAP-II

Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.

2010

VASST

Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.

2008

CORTICUS

Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.

2008

APROCCHSS

Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.

2018

ADRENAL

Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.

2018

TRISS

Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.

2014

TRICC

Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.

1999

PLCO

PLCO: PSA screening did not reduce prostate cancer mortality; annual CXR did not reduce lung cancer mortality.

2012

NORDICC

Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.

2022

NELSON

Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.

2020

MILES

NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.

2011

WHISH

Multiple women's health prevention trials informed lifestyle guidance; activity recommendations widely cited.

2017

PREDIMED

Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.

2013

INTERACT2

Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.

2013

FIELD

Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.

2005

ROSC

BACKGROUND: Exhaled end-tidal carbon dioxide (EtCO 2 ) trajectory is associated with out-of-hospital cardiac arrest (OHCA) outcomes.

2026

WSG

PURPOSE The WSG TP-II trial (ClinicalTrials.gov identifier: NCT03272477 ) was designed to compare the impact of 12 weeks of neoadjuvant trastuzumab + pertuzumab combined with endocrine therapy (ET) ve

MINT

BACKGROUND: The optimal transfusion strategy in patients with acute myocardial infarction (AMI) and anemia may be influenced by sex differences in pathophysiology and cardiovascular outcomes.

PURE

PURE study: high carbohydrate intake associated with higher mortality; total fat with lower mortality globally.

2017

SALT

SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.

2021

TONE

Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.

1998

DASH-Sodium

Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.

2001

DASH

DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.

1997

STAREE

STAREE will assess atorvastatin in older adults for disability-free survival; reflects elderly statin question.

2025

ALLHAT-LLT

Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.

2002

PolyIran

Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.

2019

TIPS

TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.

2021

VITAL-Bone

Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.

2022

D2d

Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.

2019

WHI

Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.

2006

PROVE-HF

TAME PAD: TAILORed prevention efforts in peripheral arterial disease; multidisciplinary intervention outcomes mixed.

2023

COMPASS

Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.

2017

MEGA

Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.

2006

PROSPER

Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.

2002

SPRINT-MIND

Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.

2019

EAGLES

Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.

2016

HOPE

Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.

2000

SHEP

Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.

1991

PREDIMED-Plus

Energy-reduced Mediterranean diet plus physical activity reduced visceral adiposity and possibly CV outcomes.

2023

VITAL-Rhythm

Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.

2020

VITAL

Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.

2019

SANAD

SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.

2007

PROMISE-2

IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.

2020

EVOLVE-1

Fremanezumab anti-CGRP antibody reduced migraine days in episodic and chronic migraine prevention.

2018

STRIVE

Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.

2017

EMPOWER

MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.

2017

PHOENIX

Phase 3 PHOENIX trial showed AMX0035 did not slow ALS progression vs placebo; product was withdrawn.

2024

CENTAUR

AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.

2020

VALOR

Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.

2022

SUNBEAM

Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.

2019

FREEDOMS

Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

CLARITY

Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

ORATORIO

Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.

2017

OPERA-1

Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.

2017

EMERGE

EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.

2022

TRAILBLAZER-ALZ

Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.

2023

CLARITY-AD

Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.

2022

ANNEXA-4

Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.

2019

DEFUSE-2

Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.

2012

CRYSTAL-AF

Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.

2014

SPS3

Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.

2012

ENCHANTED

Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.

2016

ATACH-II

Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.

2016

SOCRATES

Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.

2016

THALES

Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.

2020

CHANCE

Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.

2013

POINT

Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.

2018

RESILIENT

Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.

2020

TIMELESS

Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.

2024

AcT

Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.

2022

THRACE

Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.

2016

SWIFT-PRIME

Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.

2015

REVASCAT

Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.

2015

EXTEND-IA

Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.

2015

ESCAPE

Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.

2015

MR CLEAN

Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.

2015

IST-3

IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.

2012

ECASS-3

IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.

2008

MERIT

BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.

2013

ACCORD-Lipid

Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.

2010

VERIFY

Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.

2019

HALO-Influenza

High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.

2014

FLAURA2

Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.

2023

RELATIVITY-047

Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.

2022

CANTATA-SU

Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.

2013

EMPULSE

Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.

2022

SELECT-CKD

Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.

2024

STEP-HFpEF

Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.

2024

SCALE

Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.

2015

ACCORD-MIND

Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.

2011

Look

Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.

2012

REWIND-CKD

AWARD-7: dulaglutide preserved eGFR and reduced albuminuria in T2D with moderate to severe CKD.

2018

DELIVER

Placeholder twin endocrine entries — see SURPASS series for additional tirzepatide outcomes.

2024

ACHIEVE-1

Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.

2025

OASIS-1

Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.

2023

STEP

Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.

2022

DPP

Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.

2002

LookAHEAD

Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.

2013

GRADE

Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.

2022

SURPASS-4

Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.

2021

SURPASS-3

Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.

2021

SURPASS-2

Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.

2021

SURMOUNT-1

Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.

2022

DEVOTE

Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.

2017

ORIGIN

Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.

2012

CARMELINA

Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.

2019

CAROLINA

Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.

2019

ELIXA

Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.

2015

HARMONY

Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.

2018

AMPLITUDE-O

Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.

2021

PIONEER-6

Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.

2019

REWIND

Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.

2019

EXAMINE

Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.

2013

SAVOR-TIMI

Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.

2013

TECOS

Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.

2015

ACCORD

Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.

2008

VADT

Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.

2009

ADVANCE

Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.

2008

GISAID

Opposites Attract: no linked HIV transmissions among MSM serodiscordant couples when HIV-positive partner virally suppressed.

2018

CAPiTA

PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.

2015

PNEUMOSIL

PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to PCV13 for IgG responses in infants.

2020

ACTT-2

Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.

2021

ACTIV-2

COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.

2021

STOP-TB

TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.

2011

FLU-IVIG

Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.

2019

OFLOTUB

Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.

2014

STREAM

9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.

2019

Nix-TB

BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.

2020

STAND

Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.

2021

REMoxTB

4-month moxifloxacin-containing regimens were non-inferior to standard 6-month therapy for drug-susceptible TB only weakly.

2014

C-EDGE

Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.

2015

ION-1

Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.

2014

ASTRAL-1

Sofosbuvir-velpatasvir achieved high SVR12 across HCV genotypes 1-6, establishing pan-genotypic therapy.

2015

MERINO

Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.

2018

MATISSE

Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.

2023

MELODY

Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.

2022

RENOIR

Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.

2023

ZOE-50

Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.

2016

R21

R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.

2023

RTS,S

RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.

2015

MOVe-OUT

Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.

2022

iPrEx

Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.

2010

MajesTEC-1

Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.

2022

NOAH

Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.

2010

PAOLA-1

Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.

2019

CLEAR

Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.

2021

WOEST

Warfarin + clopidogrel vs triple therapy after PCI in patients on OAC — reduced bleeding without ischemic penalty.

2013

ENSEMBLE

Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.

2021

ChAdOx1

ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.

2021

NVX-CoV2373

Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.

2021

ACTIV-3

Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.

2021

PANORAMIC

Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.

2022

EPIC-HR

Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.

2022

COV-BARRIER

Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.

2021

EMPACTA

Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.

2021

COVACTA

Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.

2021

REMAP-CAP

Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.

2021

PURPOSE-2

Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.

2024

PURPOSE-1

Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.

2024

HPTN-083

Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.

2021

DISCOVER

F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.

2020

SMART

Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.

2006

TEMPRANO

Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.

2015

START

Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.

2015

HPTN-052

Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.

2011

MAGIC

Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.

2006

CROSS

Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.

2012

EPCORE

Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.

2023

TOURMALINE-MM1

Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.

2016

EMILIA

T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.

2012

AURA3

Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.

2017

IDEA

IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.

2018

X-ACT

Adjuvant capecitabine non-inferior to 5-FU/LV in stage III colon cancer with better tolerability.

2005

MOSAIC

Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.

2004

CheckMate-067

Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.

2017

CheckMate-577

Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.

2021

KEYNOTE-590

Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.

2021

PALOMA-3

Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.

2015

MONALEESA-2

Ribociclib plus letrozole improved PFS and OS in postmenopausal HR+/HER2- advanced breast cancer.

2016

PALOMA-2

Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.

2016

OlympiA

One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.

2021

RAPIDO

Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.

2020

PRODIGE

Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.

2021

NAPOLI-3

NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.

2023

TOPAZ-1

Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.

2022

POSEIDON

Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.

2022

ALEX

Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.

2017

CROWN

Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.

2020

TROPION-Lung01

Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.

2023

PACIFIC-2

Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.

2024

KRYSTAL-1

Adagrasib produced responses in KRAS G12C-mutated NSCLC and colorectal cancer.

2022

CodeBreaK

Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.

2021

MARIPOSA

Amivantamab plus lazertinib improved PFS vs osimertinib in first-line EGFR-mutated advanced NSCLC.

2023

MAGNITUDE

Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.

2022

PROfound

Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.

2020

NOVA

Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.

2016

PRIMA

Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.

2019

SOLO-1

Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.

2018

EV-302

Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.

2023

CheckMate-214

Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.

2018

KEYNOTE-426

Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.

2019

KEYNOTE-054

Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.

2018

COMBI-AD

Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.

2017

MAIA

Daratumumab plus Rd improved PFS and OS in transplant-ineligible newly diagnosed multiple myeloma.

2019

ADAURA

Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.

2020

TRILUMINATE

Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.

2023

MITRA-HR

MitraClip plus medical therapy vs medical alone in secondary MR — outcomes differed between COAPT and MITRA-FR cohorts.

2018

COLCOT

Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.

2019

ECHELON-1

Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.

2018

POLARIX

Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.

2022

CASTOR

Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.

2016

ALCYONE

Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.

2018

CARTITUDE-4

Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.

2023

CARTITUDE-1

Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.

2021

KarMMa

Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.

2021

ZUMA-7

Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.

2022

ZUMA-1

Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.

2017

RUBY

Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.

2023

KEYNOTE-826

Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.

2021

ARASENS

Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.

2022

TITAN

Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.

2019

LATITUDE

Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.

2017

STAMPEDE

Multi-arm trial showing docetaxel and abiraterone added to ADT improved survival in metastatic hormone-sensitive prostate cancer.

2017

IMbrave150

Atezolizumab plus bevacizumab improved OS and PFS vs sorafenib in unresectable hepatocellular carcinoma.

2020

CheckMate-649

Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.

2021

CALGB

Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.

2017

RxPONDER

Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.

2021

MINDACT

MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.

2016

TAILORx

Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.

2018

HER2CLIMB

Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.

2020

ASCENT

Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.

2021

TROPiCS-02

Sacituzumab govitecan improved PFS and OS in pretreated HR+/HER2- metastatic breast cancer.

2022

DESTINY-Breast04

T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.

2022

DESTINY-Breast03

Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.

2022

monarchE

Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.

2020

KEYNOTE-522

Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.

2020

CheckMate-816

Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.

2022

IMpower010

Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.

2021

OPTIC

Amiodarone + beta-blocker vs sotalol vs beta-blocker alone for ICD shock prevention — amiodarone combo most effective.

2006

PARTITA

VT ablation after first appropriate ICD shock vs continued medical therapy — reduced death/VT storm.

2022

VANISH

Catheter ablation vs escalated antiarrhythmic therapy in recurrent VT — reduced composite of death/VT storm/ICD shocks.

2016

MADIT-RIT

High-rate or delayed ICD therapy vs conventional programming — reduced inappropriate shocks and mortality.

2012

PERIOP-2

LMWH bridging vs placebo during warfarin interruption in high-risk AF/mechanical valves — no benefit, more bleeding.

2021

PAUSE

Standardized DOAC interruption strategy in AF undergoing surgery — low rates of bleeding and thromboembolism.

2019

BRIDGE

Bridging anticoagulation vs no bridging during warfarin interruption in AF — no thromboembolism reduction, more bleeding.

2015

ENTRUST-AF-PCI

Edoxaban-based dual therapy vs warfarin triple therapy after PCI in AF — non-inferior bleeding endpoint.

2019

PIONEER-AF-PCI

Rivaroxaban-based vs warfarin triple therapy after PCI in AF — reduced clinically significant bleeding.

2016

RE-DUAL

Dabigatran + P2Y12 inhibitor vs warfarin triple therapy after PCI in AF — less bleeding, non-inferior thromboembolism.

2017

MANAGE

Dabigatran in perioperative MI/myocardial injury after non-cardiac surgery — reduced major vascular complications.

2018

MATRIX

Radial vs femoral access and bivalirudin vs heparin in ACS — radial reduced major bleeding and net adverse events.

2015

RIVAL

Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.

2011

EVERESTII

MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.

2011

RECOVERY

Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.

2020

AVATAR

Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.

2021

EARLY-TAVR

Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.

2024

SURTAVI

Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.

2017

DAPA-MI

Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.

2023

EMPACT-MI

Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.

2024

LoDoCo2

Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.

2020

CANTOS

Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.

2017

TIMACS

Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.

2009

RITA-3

Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.

2002

ISCHEMIA-CKD

Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.

2020

BARI

Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.

2009

SYNTAX

PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.

2009

COMPLETE

Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.

2019

DANAMI-3

FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.

2015

ECLS-SHOCK

VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.

2023

IABP-SHOCK

IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.

2012

REVEAL

Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.

2017

AFCAPS

Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.

1998

VALOR-HCM

Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.

2022

SHOCK

Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.

1999

CULPRIT-SHOCK

Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.

2017

HOST-EXAM

Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.

2021

MASTER-DAPT

1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.

2021

STOPDAPT-2

1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.

2019

TWILIGHT

Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.

2019

TRITON-TIMI

Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.

2007

PLATO

Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.

2009

TIMI

Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.

1999

GUSTO-I

Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.

1993

ISIS-2

Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.

1988

ATLAS

Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.

2012

ACTIVE-W

Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.

2006

ACTIVE-A

Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.

2009

EARLY-AF

Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.

2021

STOP-AF

Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.

2021

PRAGUE-17

LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.

2020

PREVAIL

Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.

2014

PROTECT-AF

Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.

2009

ATHENA

Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.

2009

RACE

Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.

2002

AFFIRM

Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.

2002

PROMINENT

Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.

2022

STRENGTH

Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.

2020

ORION-11

Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.

2020

ORION-10

Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.

2020

AIM-HIGH

Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.

2011

HPS2-THRIVE

Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.

2014

HPS

Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.

2002

TNT

Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.

2005

PROVE-IT

High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.

2004

WOSCOPS

Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.

1995

RADIANCE-HTN

Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.

2018

VALUE

Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.

2004

INVEST

Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.

2003

PATHWAY-2

Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.

2015

SYMPLICITY

Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.

2014

ACCOMPLISH

Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.

2008

ASCOT-BPLA

Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.

2005

LIFE

Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.

2002

HYVET

Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.

2008

ATTR-ACT

Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.

2018

EXPLORER-HCM

Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.

2020

CHAMPION

Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.

2011

DANISH

Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.

2016

RAFT

CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.

2010

MADIT-CRT

CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.

2009

CARE-HF

CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.

2005

COMPANION

CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.

2004

MADIT-II

Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.

2002

SCD-HeFT

ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.

2005

A-HeFT

Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.

2004

AIRE

Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.

1993

SAVE

Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.

1992

I-PRESERVE

Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.

2008

CHARM-Alternative

Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.

2003

Val-HeFT

Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.

2001

CONSENSUS

Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.

1987

SOLVD

Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.

1991

COPERNICUS

Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.

2001

CIBIS-II

Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.

1999

MERIT-HF

Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.

1999

EPHESUS

Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.

2003

RALES

Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.

1999

TOPCAT

Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.

2014

ProCESS

Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.

2014

SUSTAIN-6

Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.

2016

ATTAIN-MAINTAIN

Abstract Incretins have improved the management of obesity and its related complications, but maintaining these health benefits requires ongoing administration, which can be challenging.

2026

SURMOUNT-MAINTAIN

Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial

2026

DCCT

Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.

1993

CAST

Encainide/flecainide vs placebo to suppress PVCs post-MI — increased mortality; pivotal negative trial.

1991

Women's

Hormone replacement (estrogen + progestin) in postmenopausal women — increased breast cancer and CVD; stopped early.

2002

ARRIVE

Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.

2018

ASCEND

Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.

2014

INPULSIS-1

Nintedanib in IPF — slowed FVC decline.

2014

CAPACITY

Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.

2011

ANDROMEDA-SHOCK

Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.

2019

CESAR

ECMO referral in severe respiratory failure — improved 6-month outcomes.

2009

ARDSnet

Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.

2000

NETTER-1

177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.

2017

EMBRACA

Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.

2018

KATHERINE

T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.

2019

APHINITY

Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.

2017

CLEOPATRA

Pertuzumab + trastuzumab + docetaxel in HER2+ metastatic breast cancer — major overall survival benefit.

2012

IMpassion130

Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).

2018

PACIFIC

Durvalumab consolidation after chemoradiation in stage III NSCLC — major PFS and OS benefit.

2017

FLAURA

First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — PFS and OS benefit.

2017

CheckMate-067

Nivolumab + ipilimumab vs monotherapy in advanced melanoma — durable long-term OS benefit with combination.

2015

KEYNOTE-407

First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.

2018

KEYNOTE-189

First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.

2018

KEYNOTE-024

First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.

2016

ASPREE

Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.

2018

mRNA-1273

Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.

2020

BNT162b2

Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.

2020

WHO

WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.

2020

ACTT-1

Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.

2020

WAKE-UP

IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.

2018

EXTEND

IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.

2019

DEFUSE-3

Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.

2018

DAWN

Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.

2017

NINDS

IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.

1995

UKPDS

Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.

1998

STEP-HFpEF

Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.

2023

STEP

Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.

2021

FLOW

Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.

2024

SELECT

Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.

2023

DAPA-CKD

Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.

2020

CREDENCE

Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.

2019

CANVAS

Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.

2017

DECLARE-TIMI

Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.

2018

LEADER

Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.

2016

EMPA-REG

Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.

2015

AUGUSTUS

Antithrombotic strategies in AF + ACS/PCI — apixaban without aspirin reduced bleeding without raising ischemic events.

2019

POISE-2

Perioperative aspirin and clonidine in non-cardiac surgery — neither reduced CV events; aspirin increased bleeding.

2014

POISE

Perioperative metoprolol in non-cardiac surgery — fewer MIs but more strokes and total deaths.

2008

MITRA-FR

MitraClip + medical therapy vs medical therapy alone in HF with secondary MR — no benefit (contrast COAPT).

2018

COAPT

MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.

2018

Evolut

Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.

2019

PARTNER

TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.

2019

PARTNER

TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.

2016

PARTNER

TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.

2011

PEGASUS-TIMI

Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.

2015

ISAR-REACT

Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.

2019

FAME

FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.

2012

FAME

FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.

2009

NOBLE

PCI vs CABG in left main CAD — CABG superior on composite endpoint.

2016

EXCEL

PCI vs CABG in left main CAD — similar 5-year composite outcomes; controversial 10-year mortality signal.

2016

FREEDOM

CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.

2012

ORBITA-2

PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.

2023

ORBITA

PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.

2017

COURAGE

PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.

2007

AVERROES

Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.

2011

CASTLE-AF

Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.

2018

EAST-AFNET

Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.

2020

CABANA

Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).

2019

ARISTOTLE

Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.

2011

ROCKET-AF

Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.

2011

RE-LY

Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.

2009

4S Scandinavian

Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.

1994

CLEAR

Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.

2023

REDUCE-IT

Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.

2019

ODYSSEY

Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.

2018

FOURIER

Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.

2017

IMPROVE-IT

Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.

2015

ALLHAT

First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.

2002

STEP

Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.

2021

HOPE-3

Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.

2016

EMPHASIS-HF

Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.

2011

SHIFT

Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.

2010

CHARM-Added

Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.

2003

FINEARTS-HF

Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.

2024

STRONG-HF

High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.

2022

VICTORIA

Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.

2020

GALACTIC-HF

Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.

2021

PIONEER-HF

Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.

2019

DELIVER

Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.

2022

EMPEROR-Preserved

Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.

2021

ONTARGET

Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.

2008

STICH

CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — long-term mortality benefit with CABG.

2011

RECOVERY

Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.

2021

ACCORD-BP

Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.

2010

ISCHEMIA

Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.

2020

COMPASS

Low-dose rivaroxaban + aspirin vs aspirin alone in stable CAD/PAD — reduced major CV events.

2017

PARADIGM-HF

Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.

2014

EMPEROR-Reduced

Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.

2020

DAPA-HF

Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.

2019

SPRINT

Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.

2015

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