Library
Landmark Trials
A curated reference of foundational trials in medicine — selected for clinical impact and teaching value.
Heart Failure
41 trialsA-HeFT
Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.
2004AC01
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,
2026AIRE
Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.
1993ATTR-ACT
Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.
2018CARE-HF
CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.
2005CHAMPION
Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.
2011CHARM-Added
Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.
2003CHARM-Alternative
Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.
2003CIBIS-II
Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.
1999COMPANION
CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.
2004CONSENSUS
Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.
1987COPERNICUS
Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.
2001DANISH
Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.
2016DAPA
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
2026DAPA-HF
Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.
2019DELIVER
Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.
2022EMPEROR-Preserved
Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.
2021EMPEROR-Reduced
Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.
2020EMPHASIS-HF
Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.
2011EPHESUS
Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.
2003EXPLORER-HCM
Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.
2020FINEARTS-HF
Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.
2024GALACTIC-HF
Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.
2021I-PRESERVE
Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.
2008MADIT-CRT
CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.
2009MADIT-II
Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.
2002MERIT-HF
Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.
1999PARADIGM-HF
Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.
2014PIONEER-HF
Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.
2019RAFT
CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.
2010RALES
Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.
1999SAVE
Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.
1992SCD-HeFT
ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.
2005SGLT2
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
2026SHIFT
Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.
2010SOLVD
Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.
1991STRONG-HF
High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.
2022TOPCAT
Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.
2014Val-HeFT
Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.
2001VALOR-HCM
Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.
2022VICTORIA
Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.
2020Hypertension
14 trialsACCOMPLISH
Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.
2008ACCORD-BP
Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.
2010ALLHAT
First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.
2002ASCOT-BPLA
Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.
2005HOPE-3
Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.
2016HYVET
Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.
2008INVEST
Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.
2003LIFE
Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.
2002PATHWAY-2
Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.
2015RADIANCE-HTN
Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.
2018SPRINT
Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.
2015STEP
Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.
2021SYMPLICITY
Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.
2014VALUE
Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.
2004Lipid Management
18 trials4S Scandinavian
Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.
1994AFCAPS
Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.
1998AIM-HIGH
Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.
2011CLEAR
Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.
2023FOURIER
Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.
2017HPS
Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.
2002HPS2-THRIVE
Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.
2014IMPROVE-IT
Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.
2015ODYSSEY
Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.
2018ORION-10
Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.
2020ORION-11
Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.
2020PROMINENT
Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.
2022PROVE-IT
High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.
2004REDUCE-IT
Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.
2019REVEAL
Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.
2017STRENGTH
Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.
2020TNT
Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.
2005WOSCOPS
Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.
1995Atrial Fibrillation
19 trialsACTIVE-A
Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.
2009ACTIVE-W
Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.
2006AFFIRM
Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.
2002ARISTOTLE
Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.
2011ATHENA
Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.
2009ATLAS
Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.
2012AVERROES
Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.
2011CABANA
Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).
2019CASTLE-AF
Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.
2018EARLY-AF
Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.
2021EAST-AFNET
Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.
2020PFA-SHAM
BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.
2026PRAGUE-17
LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.
2020PREVAIL
Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.
2014PROTECT-AF
Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.
2009RACE
Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.
2002RE-LY
Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.
2009ROCKET-AF
Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.
2011STOP-AF
Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.
2021Coronary Artery Disease
42 trialsBARI
Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.
2009CANTOS
Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.
2017COLCOT
Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.
2019COMPASS
Low-dose rivaroxaban + aspirin vs aspirin alone in stable CAD/PAD — reduced major CV events.
2017COMPLETE
Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.
2019COURAGE
PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.
2007CULPRIT-SHOCK
Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.
2017DANAMI-3
FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.
2015DAPA-MI
Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.
2023ECLS-SHOCK
VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.
2023EMPACT-MI
Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.
2024EXCEL
PCI vs CABG in left main CAD — similar 5-year composite outcomes; controversial 10-year mortality signal.
2016FAME
FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.
2009FAME
FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.
2012FREEDOM
CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.
2012GUSTO-I
Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.
1993HOST-EXAM
Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.
2021IABP-SHOCK
IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.
2012ISAR-REACT
Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.
2019ISCHEMIA
Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.
2020ISCHEMIA-CKD
Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.
2020ISIS-2
Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.
1988LoDoCo2
Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.
2020MASTER-DAPT
1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.
2021MATRIX
Radial vs femoral access and bivalirudin vs heparin in ACS — radial reduced major bleeding and net adverse events.
2015MINT
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.
2016ONTARGET
Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.
2008ORBITA
PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.
2017ORBITA-2
PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.
2023PEGASUS-TIMI
Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.
2015PLATO
Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.
2009RITA-3
Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.
2002RIVAL
Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.
2011SHOCK
Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.
1999STICH
CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — long-term mortality benefit with CABG.
2011STOPDAPT-2
1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.
2019SYNTAX
PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.
2009TIMACS
Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.
2009TIMI
Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.
1999TRITON-TIMI
Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.
2007TWILIGHT
Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.
2019Valvular Heart Disease
14 trialsAVATAR
Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.
2021COAPT
MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.
2018EARLY-TAVR
Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.
2024EVERESTII
MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.
2011Evolut
Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.
2019MITRA-FR
MitraClip + medical therapy vs medical therapy alone in HF with secondary MR — no benefit (contrast COAPT).
2018MITRA-HR
MitraClip plus medical therapy vs medical alone in secondary MR — outcomes differed between COAPT and MITRA-FR cohorts.
2018NOTION-3
Impact of Angina on Outcome After Percutaneous Coronary Intervention in Patients Undergoing Transcatheter Aortic Valve Implantation: Insights From the NOTION-3 Trial
2026PARTNER
TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.
2011PARTNER
TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.
2016PARTNER
TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.
2019RECOVERY
Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.
2020SURTAVI
Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.
2017TRILUMINATE
Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.
2023Perioperative & Antithrombotic
11 trialsAUGUSTUS
Antithrombotic strategies in AF + ACS/PCI — apixaban without aspirin reduced bleeding without raising ischemic events.
2019BRIDGE
Bridging anticoagulation vs no bridging during warfarin interruption in AF — no thromboembolism reduction, more bleeding.
2015ENTRUST-AF-PCI
Edoxaban-based dual therapy vs warfarin triple therapy after PCI in AF — non-inferior bleeding endpoint.
2019MANAGE
Dabigatran in perioperative MI/myocardial injury after non-cardiac surgery — reduced major vascular complications.
2018PAUSE
Standardized DOAC interruption strategy in AF undergoing surgery — low rates of bleeding and thromboembolism.
2019PERIOP-2
LMWH bridging vs placebo during warfarin interruption in high-risk AF/mechanical valves — no benefit, more bleeding.
2021PIONEER-AF-PCI
Rivaroxaban-based vs warfarin triple therapy after PCI in AF — reduced clinically significant bleeding.
2016POISE
Perioperative metoprolol in non-cardiac surgery — fewer MIs but more strokes and total deaths.
2008POISE-2
Perioperative aspirin and clonidine in non-cardiac surgery — neither reduced CV events; aspirin increased bleeding.
2014RE-DUAL
Dabigatran + P2Y12 inhibitor vs warfarin triple therapy after PCI in AF — less bleeding, non-inferior thromboembolism.
2017WOEST
Warfarin + clopidogrel vs triple therapy after PCI in patients on OAC — reduced bleeding without ischemic penalty.
2013Cardiac Arrhythmia
5 trialsCAST
Encainide/flecainide vs placebo to suppress PVCs post-MI — increased mortality; pivotal negative trial.
1991MADIT-RIT
High-rate or delayed ICD therapy vs conventional programming — reduced inappropriate shocks and mortality.
2012OPTIC
Amiodarone + beta-blocker vs sotalol vs beta-blocker alone for ICD shock prevention — amiodarone combo most effective.
2006PARTITA
VT ablation after first appropriate ICD shock vs continued medical therapy — reduced death/VT storm.
2022VANISH
Catheter ablation vs escalated antiarrhythmic therapy in recurrent VT — reduced composite of death/VT storm/ICD shocks.
2016Diabetes & Cardiometabolic
55 trialsACCORD
Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.
2008ACCORD-Lipid
Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.
2010ACCORD-MIND
Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.
2011ACHIEVE-1
Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.
2025ACHIEVE-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
2026ADVANCE
Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.
2008AMPLITUDE-O
Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.
2021ATTAIN-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.
2026CANTATA-SU
Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.
2013CANVAS
Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.
2017CARMELINA
Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.
2019CAROLINA
Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.
2019CREDENCE
Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.
2019DAPA-CKD
Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.
2020DECLARE-TIMI
Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.
2018DELIVER
Placeholder twin endocrine entries — see SURPASS series for additional tirzepatide outcomes.
2024DEVOTE
Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.
2017DPP
Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.
2002ELIXA
Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.
2015EMPA-REG
Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.
2015EMPULSE
Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.
2022EXAMINE
Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.
2013FIELD
Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.
2005FLOW
Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.
2024GRADE
Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.
2022HARMONY
Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.
2018LEADER
Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.
2016Look
Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.
2012LookAHEAD
Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.
2013MERIT
BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.
2013OASIS-1
Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.
2023ORIGIN
Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.
2012PIONEER-6
Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.
2019REIMAGINE
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
2026REWIND
Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.
2019REWIND-CKD
AWARD-7: dulaglutide preserved eGFR and reduced albuminuria in T2D with moderate to severe CKD.
2018SAVOR-TIMI
Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.
2013SCALE
Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.
2015SELECT
Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.
2023SELECT-CKD
Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.
2024STEP
Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.
2021STEP
Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.
2022STEP-HFpEF
Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.
2023STEP-HFpEF
Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.
2024SURMOUNT-1
Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.
2022SURMOUNT-2
Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.
2023SURMOUNT-MAINTAIN
Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial
2026SURPASS-2
Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.
2021SURPASS-3
Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.
2021SURPASS-4
Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.
2021SUSTAIN-6
Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.
2016TECOS
Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.
2015UKPDS
Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.
1998VADT
Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.
2009VERIFY
Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.
2019Stroke & Acute Neurology
44 trialsAcT
Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.
2022ANNEXA-4
Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.
2019ATACH-II
Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.
2016ATTRACTION
Efficacy and safety of tirofiban after successful endovascular reperfusion in acute ischaemic stroke (ATTRACTION) in China: a multicentre, double-blind, randomised controlled trial
2026CENTAUR
AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.
2020CHANCE
Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.
2013CLARITY
Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.
2010CLARITY-AD
Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.
2022CRYSTAL-AF
Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.
2014DAWN
Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.
2017DEFUSE-2
Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.
2012DEFUSE-3
Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.
2018ECASS-3
IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.
2008EMERGE
EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.
2022EMPOWER
MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.
2017ENCHANTED
Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.
2016ESCAPE
Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.
2015EVOLVE-1
Fremanezumab anti-CGRP antibody reduced migraine days in episodic and chronic migraine prevention.
2018EXTEND
IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.
2019EXTEND-IA
Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.
2015FREEDOMS
Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.
2010INTERACT2
Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.
2013IST-3
IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.
2012MR CLEAN
Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.
2015NINDS
IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.
1995OPERA-1
Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.
2017ORATORIO
Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.
2017PHOENIX
Phase 3 PHOENIX trial showed AMX0035 did not slow ALS progression vs placebo; product was withdrawn.
2024POINT
Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.
2018PROMISE-2
IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.
2020RESILIENT
Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.
2020REVASCAT
Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.
2015SANAD
SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.
2007SOCRATES
Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.
2016SPS3
Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.
2012STRIVE
Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.
2017SUNBEAM
Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.
2019SWIFT-PRIME
Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.
2015THALES
Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.
2020THRACE
Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.
2016TIMELESS
Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.
2024TRAILBLAZER-ALZ
Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.
2023VALOR
Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.
2022WAKE-UP
IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.
2018COVID-19 & Vaccines
48 trialsACTIV-2
COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.
2021ACTIV-3
Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.
2021ACTT-1
Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.
2020ACTT-2
Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.
2021ASTRAL-1
Sofosbuvir-velpatasvir achieved high SVR12 across HCV genotypes 1-6, establishing pan-genotypic therapy.
2015BNT162b2
Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.
2020C-EDGE
Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.
2015CAPiTA
PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.
2015ChAdOx1
ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.
2021COV-BARRIER
Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.
2021COVACTA
Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.
2021DISCOVER
F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.
2020EMPACTA
Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.
2021ENSEMBLE
Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.
2021EPIC-HR
Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.
2022FLU-IVIG
Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.
2019GISAID
Opposites Attract: no linked HIV transmissions among MSM serodiscordant couples when HIV-positive partner virally suppressed.
2018HALO-Influenza
High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.
2014HPTN-052
Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.
2011HPTN-083
Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.
2021ION-1
Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.
2014iPrEx
Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.
2010MATISSE
Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.
2023MELODY
Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.
2022MERINO
Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.
2018MOVe-OUT
Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.
2022mRNA-1273
Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.
2020Nix-TB
BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.
2020NVX-CoV2373
Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.
2021OFLOTUB
Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.
2014PANORAMIC
Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.
2022PNEUMOSIL
PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to PCV13 for IgG responses in infants.
2020PURPOSE-1
Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.
2024PURPOSE-2
Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.
2024R21
R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.
2023RECOVERY
Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.
2021REMAP-CAP
Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.
2021REMoxTB
4-month moxifloxacin-containing regimens were non-inferior to standard 6-month therapy for drug-susceptible TB only weakly.
2014RENOIR
Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.
2023RTS,S
RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.
2015SMART
Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.
2006STAND
Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.
2021START
Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.
2015STOP-TB
TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.
2011STREAM
9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.
2019TEMPRANO
Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.
2015WHO
WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.
2020ZOE-50
Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.
2016Oncology
106 trialsADAURA
Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.
2020ALCYONE
Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.
2018ALEX
Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.
2017APHINITY
Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.
2017ARASENS
Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.
2022ASCENT
Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.
2021AURA3
Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.
2017CALGB
Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.
2017CARTITUDE-1
Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.
2021CARTITUDE-4
Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.
2023CASTOR
Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.
2016CheckMate-067
Nivolumab + ipilimumab vs monotherapy in advanced melanoma — durable long-term OS benefit with combination.
2015CheckMate-067
Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.
2017CheckMate-214
Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.
2018CheckMate-577
Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.
2021CheckMate-649
Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.
2021CheckMate-816
Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.
2022CHOP
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
2026CLEAR
Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.
2021CLEOPATRA
Pertuzumab + trastuzumab + docetaxel in HER2+ metastatic breast cancer — major overall survival benefit.
2012CodeBreaK
Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.
2021COMBI-AD
Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.
2017COMPPARE
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
2026CROSS
Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.
2012CROWN
Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.
2020DESTINY-Breast03
Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.
2022DESTINY-Breast04
T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.
2022ECHELON-1
Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.
2018EMBRACA
Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.
2018EMILIA
T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.
2012EPCORE
Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.
2023EV-302
Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.
2023FLAURA
First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — PFS and OS benefit.
2017FLAURA2
Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.
2023GLP-1
10559 Background: Lung cancer (LC) is the leading cause of cancer-related mortality in the United States.
2026HER2
39 Background: The benefit of adjuvant chemotherapy in premenopausal women with hormone receptor (HR)–positive, HER2-negative early breast cancer remains controversial.
2026HER2
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
2026HER2CLIMB
Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.
2020IDEA
IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.
2018III
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.
2020IMpassion130
Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).
2018IMpower010
Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.
2021JCOG1008
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
2022KarMMa
Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.
2021KATHERINE
T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.
2019KEYNOTE-024
First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.
2016KEYNOTE-054
Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.
2018KEYNOTE-189
First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.
2018KEYNOTE-407
First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.
2018KEYNOTE-426
Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.
2019KEYNOTE-522
Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.
2020KEYNOTE-590
Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.
2021KEYNOTE-826
Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.
2021KRYSTAL-1
Adagrasib produced responses in KRAS G12C-mutated NSCLC and colorectal cancer.
2022LATITUDE
Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.
2017MAGIC
Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.
2006MAGNITUDE
Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.
2022MAIA
Daratumumab plus Rd improved PFS and OS in transplant-ineligible newly diagnosed multiple myeloma.
2019MajesTEC-1
Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.
2022MALDI-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.
2023MINDACT
MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.
2016MONALEESA-2
Ribociclib plus letrozole improved PFS and OS in postmenopausal HR+/HER2- advanced breast cancer.
2016monarchE
Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.
2020MOSAIC
Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.
2004NAPOLI-3
NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.
2023NEMIO
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
2026NETTER-1
177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.
2017NOAH
Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.
2010NOVA
Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.
2016OlympiA
One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.
2021PACIFIC
Durvalumab consolidation after chemoradiation in stage III NSCLC — major PFS and OS benefit.
2017PACIFIC-2
Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.
2024PALOMA-2
Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.
2016PALOMA-3
Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.
2015PAOLA-1
Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.
2019PATHFINDER
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.
2026POLARIX
Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.
2022POSEIDON
Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.
2022PRADA
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”
2026PRIMA
Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.
2019PRODIGE
Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.
2021PROfound
Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.
2020PROFOUND
10541 Background: Early cancer detection reduces morbidity and mortality, but current recommended screening in China misses many lethal cancers.
2026RAPIDO
Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.
2020RELATIVITY-047
Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.
2022RUBY
Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.
2023RxPONDER
Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.
2021SEZ6
Abstract Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms.
2026SOLO-1
Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.
2018STAMPEDE
Multi-arm trial showing docetaxel and abiraterone added to ADT improved survival in metastatic hormone-sensitive prostate cancer.
2017SUCCESSOR-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
2026TAILORx
Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.
2018TITAN
Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.
2019TOPAZ-1
Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.
2022TOURMALINE-MM1
Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.
2016TRACE
102 Background: Gastric cancer, a leading global malignancy with high incidence and mortality, poses a significant public health burden in China.
2026TROPiCS-02
Sacituzumab govitecan improved PFS and OS in pretreated HR+/HER2- metastatic breast cancer.
2022TROPION-Lung01
Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.
2023TXI
10582 Background: Colonoscopy remains the gold standard for preventing colorectal cancer;
2026WGS
202 Background: Ovarian cancer, including fallopian tube and primary peritoneal carcinoma, is often diagnosed at advanced stages.
2026WSG
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.
2005ZUMA-1
Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.
2017ZUMA-7
Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.
2022Critical Care
33 trials65 trial
Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.
20206S hydroxyethyl
Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.
2012ADRENAL
Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.
2018ANDROMEDA-SHOCK
Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.
2019APROCCHSS
Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.
2018ARDSnet
Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.
2000ARISE
Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.
2014ART
Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.
2017BaSICS
Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.
2021CESAR
ECMO referral in severe respiratory failure — improved 6-month outcomes.
2009CHEST
Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.
2012CORTICUS
Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.
2008CRASH-2
Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.
2010CRASH-3
Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.
2019EOLIA
Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.
2018EPaNIC
Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.
2011NICE-SUGAR
Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.
2009PEPTIC
Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.
2020PLUS
Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.
2022ProCESS
Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.
2014ProMISe
EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.
2015PROSEVA
Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).
2013ROSC
BACKGROUND: Exhaled end-tidal carbon dioxide (EtCO 2 ) trajectory is associated with out-of-hospital cardiac arrest (OHCA) outcomes.
2026ROSE
Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.
2019SAFE
4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.
2004SALT-ED
Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.
2018SNAP
Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority r
2026SOAP-II
Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.
2010SUP-ICU
Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.
2018TARGET
Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.
2018TRICC
Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.
1999TRISS
Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.
2014VASST
Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.
2008Pulmonary Disease
28 trialsAMBITION
Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.
2015ASCEND
Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.
2014BOREAS
Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).
2023CAPACITY
Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.
2011CHEST-1
Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.
2013DREAM
Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.
2012ETHOS
Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.
2020FLAME
LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.
2016GRIPHON
Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.
2015IMPACT
Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.
2018INBUILD
Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.
2019INPULSIS-1
Nintedanib in IPF — slowed FVC decline.
2014INPULSIS-2
Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.
2014LIBERTY
Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.
2022MENSA
Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.
2014NAVIGATOR
Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.
2021NOTUS
NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.
2024PATENT-1
Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.
2013POET-COPD
Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.
2011QUEST
Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.
2018SENSCIS
Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.
2019SERAPHIN
Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.
2013SIRIUS
Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.
2014STELLAR
Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.
2023TORCH
Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.
2007TRIBUTE
Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.
2018UPLIFT
Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.
2008WISDOM
Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.
2014Women’s Health
6 trialsCD40
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
2026HERS
Estrogen plus progestin did not reduce CHD events in women with established coronary heart disease.
1998MsFLASH
Escitalopram modestly reduced frequency and severity of menopausal hot flashes vs placebo in non-hormonal trial.
2011SKYLIGHT
Fezolinetant NK3 receptor antagonist reduced moderate-severe vasomotor symptoms in menopause vs placebo.
2023VICTORY
TMIST will compare digital breast tomosynthesis vs digital mammography for advanced breast cancer outcomes.
2025Women's
Hormone replacement (estrogen + progestin) in postmenopausal women — increased breast cancer and CVD; stopped early.
2002Obstetrics
17 trialsALPS
Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.
2016ARRIVE
Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.
2018ASPRE
Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.
2017BEAM
Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.
2008C*STAR
Pooled cerclage data informed practice for short cervix; ultrasound-indicated cerclage reduced preterm birth in selected.
2018CHAP
Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.
2022CHIPS
Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.
2015FlamingoTRA
PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.
2019GBS3
GBS3: routine antenatal screening vs risk-based did not significantly reduce early-onset neonatal GBS disease.
2024HAPO
HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.
2008MAGPIE
Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.
2002MFMU
17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.
2003MOMS
Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.
2011PRISM
Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.
2019STRIDER
Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.
2018Term
Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.
2000WOMAN
Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.
2017Primary Prevention
32 trialsALLHAT-LLT
Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.
2002ASPREE
Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.
2018COMPASS
Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.
2017D2d
Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.
2019DASH
DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.
1997DASH-Sodium
Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.
2001DCCT
Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.
1993EAGLES
Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.
2016HOPE
Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.
2000MEGA
Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.
2006MILES
NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.
2011NELSON
Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.
2020NORDICC
Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.
2022PLCO
PLCO: PSA screening did not reduce prostate cancer mortality; annual CXR did not reduce lung cancer mortality.
2012PolyIran
Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.
2019PREDIMED
Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.
2013PREDIMED-Plus
Energy-reduced Mediterranean diet plus physical activity reduced visceral adiposity and possibly CV outcomes.
2023PROSPER
Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.
2002PROVE-HF
TAME PAD: TAILORed prevention efforts in peripheral arterial disease; multidisciplinary intervention outcomes mixed.
2023PURE
PURE study: high carbohydrate intake associated with higher mortality; total fat with lower mortality globally.
2017SALT
SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.
2021SHEP
Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.
1991SPRINT-MIND
Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.
2019STAREE
STAREE will assess atorvastatin in older adults for disability-free survival; reflects elderly statin question.
2025TIPS
TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.
2021TONE
Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.
1998VITAL
Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.
2019VITAL-Bone
Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.
2022VITAL-DEP
Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.
2020VITAL-Rhythm
Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.
2020WHI
Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.
2006WHISH
Multiple women's health prevention trials informed lifestyle guidance; activity recommendations widely cited.
2017Cardiology
164 trials4S Scandinavian
Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.
1994A-HeFT
Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.
2004AC01
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,
2026ACCOMPLISH
Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.
2008ACCORD-BP
Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.
2010ACTIVE-A
Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.
2009ACTIVE-W
Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.
2006AFCAPS
Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.
1998AFFIRM
Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.
2002AIM-HIGH
Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.
2011AIRE
Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.
1993ALLHAT
First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.
2002ARISTOTLE
Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.
2011ASCOT-BPLA
Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.
2005ATHENA
Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.
2009ATLAS
Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.
2012ATTR-ACT
Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.
2018AUGUSTUS
Antithrombotic strategies in AF + ACS/PCI — apixaban without aspirin reduced bleeding without raising ischemic events.
2019AVATAR
Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.
2021AVERROES
Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.
2011BARI
Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.
2009BRIDGE
Bridging anticoagulation vs no bridging during warfarin interruption in AF — no thromboembolism reduction, more bleeding.
2015CABANA
Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).
2019CANTOS
Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.
2017CARE-HF
CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.
2005CAST
Encainide/flecainide vs placebo to suppress PVCs post-MI — increased mortality; pivotal negative trial.
1991CASTLE-AF
Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.
2018CHAMPION
Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.
2011CHARM-Added
Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.
2003CHARM-Alternative
Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.
2003CIBIS-II
Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.
1999CLEAR
Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.
2023COAPT
MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.
2018COLCOT
Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.
2019COMPANION
CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.
2004COMPASS
Low-dose rivaroxaban + aspirin vs aspirin alone in stable CAD/PAD — reduced major CV events.
2017COMPLETE
Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.
2019CONSENSUS
Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.
1987COPERNICUS
Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.
2001COURAGE
PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.
2007CULPRIT-SHOCK
Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.
2017DANAMI-3
FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.
2015DANISH
Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.
2016DAPA
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
2026DAPA-HF
Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.
2019DAPA-MI
Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.
2023DELIVER
Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.
2022EARLY-AF
Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.
2021EARLY-TAVR
Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.
2024EAST-AFNET
Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.
2020ECLS-SHOCK
VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.
2023EMPACT-MI
Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.
2024EMPEROR-Preserved
Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.
2021EMPEROR-Reduced
Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.
2020EMPHASIS-HF
Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.
2011ENTRUST-AF-PCI
Edoxaban-based dual therapy vs warfarin triple therapy after PCI in AF — non-inferior bleeding endpoint.
2019EPHESUS
Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.
2003EVERESTII
MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.
2011Evolut
Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.
2019EXCEL
PCI vs CABG in left main CAD — similar 5-year composite outcomes; controversial 10-year mortality signal.
2016EXPLORER-HCM
Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.
2020FAME
FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.
2009FAME
FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.
2012FINEARTS-HF
Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.
2024FOURIER
Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.
2017FREEDOM
CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.
2012GALACTIC-HF
Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.
2021GUSTO-I
Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.
1993HOPE-3
Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.
2016HOST-EXAM
Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.
2021HPS
Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.
2002HPS2-THRIVE
Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.
2014HYVET
Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.
2008I-PRESERVE
Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.
2008IABP-SHOCK
IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.
2012IMPROVE-IT
Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.
2015INVEST
Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.
2003ISAR-REACT
Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.
2019ISCHEMIA
Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.
2020ISCHEMIA-CKD
Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.
2020ISIS-2
Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.
1988LIFE
Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.
2002LoDoCo2
Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.
2020MADIT-CRT
CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.
2009MADIT-II
Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.
2002MADIT-RIT
High-rate or delayed ICD therapy vs conventional programming — reduced inappropriate shocks and mortality.
2012MANAGE
Dabigatran in perioperative MI/myocardial injury after non-cardiac surgery — reduced major vascular complications.
2018MASTER-DAPT
1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.
2021MATRIX
Radial vs femoral access and bivalirudin vs heparin in ACS — radial reduced major bleeding and net adverse events.
2015MERIT-HF
Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.
1999MINT
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).
2018MITRA-HR
MitraClip plus medical therapy vs medical alone in secondary MR — outcomes differed between COAPT and MITRA-FR cohorts.
2018NOBLE
PCI vs CABG in left main CAD — CABG superior on composite endpoint.
2016NOTION-3
Impact of Angina on Outcome After Percutaneous Coronary Intervention in Patients Undergoing Transcatheter Aortic Valve Implantation: Insights From the NOTION-3 Trial
2026ODYSSEY
Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.
2018ONTARGET
Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.
2008OPTIC
Amiodarone + beta-blocker vs sotalol vs beta-blocker alone for ICD shock prevention — amiodarone combo most effective.
2006ORBITA
PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.
2017ORBITA-2
PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.
2023ORION-10
Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.
2020ORION-11
Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.
2020PARADIGM-HF
Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.
2014PARTITA
VT ablation after first appropriate ICD shock vs continued medical therapy — reduced death/VT storm.
2022PARTNER
TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.
2011PARTNER
TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.
2016PARTNER
TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.
2019PATHWAY-2
Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.
2015PAUSE
Standardized DOAC interruption strategy in AF undergoing surgery — low rates of bleeding and thromboembolism.
2019PEGASUS-TIMI
Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.
2015PERIOP-2
LMWH bridging vs placebo during warfarin interruption in high-risk AF/mechanical valves — no benefit, more bleeding.
2021PFA-SHAM
BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.
2026PIONEER-AF-PCI
Rivaroxaban-based vs warfarin triple therapy after PCI in AF — reduced clinically significant bleeding.
2016PIONEER-HF
Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.
2019PLATO
Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.
2009POISE
Perioperative metoprolol in non-cardiac surgery — fewer MIs but more strokes and total deaths.
2008POISE-2
Perioperative aspirin and clonidine in non-cardiac surgery — neither reduced CV events; aspirin increased bleeding.
2014PRAGUE-17
LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.
2020PREVAIL
Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.
2014PROMINENT
Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.
2022PROTECT-AF
Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.
2009PROVE-IT
High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.
2004RACE
Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.
2002RADIANCE-HTN
Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.
2018RAFT
CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.
2010RALES
Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.
1999RE-DUAL
Dabigatran + P2Y12 inhibitor vs warfarin triple therapy after PCI in AF — less bleeding, non-inferior thromboembolism.
2017RE-LY
Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.
2009RECOVERY
Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.
2020REDUCE-IT
Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.
2019REVEAL
Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.
2017RITA-3
Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.
2002RIVAL
Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.
2011ROCKET-AF
Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.
2011SAVE
Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.
1992SCD-HeFT
ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.
2005SGLT2
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
2026SHIFT
Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.
2010SHOCK
Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.
1999SOLVD
Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.
1991SPRINT
Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.
2015STEP
Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.
2021STICH
CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — long-term mortality benefit with CABG.
2011STOP-AF
Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.
2021STOPDAPT-2
1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.
2019STRENGTH
Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.
2020STRONG-HF
High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.
2022SURTAVI
Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.
2017SYMPLICITY
Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.
2014SYNTAX
PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.
2009TIMACS
Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.
2009TIMI
Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.
1999TNT
Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.
2005TOPCAT
Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.
2014TRILUMINATE
Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.
2023TRITON-TIMI
Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.
2007TWILIGHT
Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.
2019Val-HeFT
Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.
2001VALOR-HCM
Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.
2022VALUE
Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.
2004VANISH
Catheter ablation vs escalated antiarrhythmic therapy in recurrent VT — reduced composite of death/VT storm/ICD shocks.
2016VICTORIA
Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.
2020WOEST
Warfarin + clopidogrel vs triple therapy after PCI in patients on OAC — reduced bleeding without ischemic penalty.
2013WOSCOPS
Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.
1995Endocrinology
55 trialsACCORD
Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.
2008ACCORD-Lipid
Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.
2010ACCORD-MIND
Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.
2011ACHIEVE-1
Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.
2025ACHIEVE-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
2026ADVANCE
Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.
2008AMPLITUDE-O
Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.
2021ATTAIN-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.
2026CANTATA-SU
Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.
2013CANVAS
Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.
2017CARMELINA
Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.
2019CAROLINA
Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.
2019CREDENCE
Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.
2019DAPA-CKD
Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.
2020DECLARE-TIMI
Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.
2018DELIVER
Placeholder twin endocrine entries — see SURPASS series for additional tirzepatide outcomes.
2024DEVOTE
Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.
2017DPP
Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.
2002ELIXA
Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.
2015EMPA-REG
Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.
2015EMPULSE
Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.
2022EXAMINE
Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.
2013FIELD
Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.
2005FLOW
Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.
2024GRADE
Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.
2022HARMONY
Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.
2018LEADER
Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.
2016Look
Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.
2012LookAHEAD
Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.
2013MERIT
BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.
2013OASIS-1
Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.
2023ORIGIN
Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.
2012PIONEER-6
Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.
2019REIMAGINE
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
2026REWIND
Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.
2019REWIND-CKD
AWARD-7: dulaglutide preserved eGFR and reduced albuminuria in T2D with moderate to severe CKD.
2018SAVOR-TIMI
Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.
2013SCALE
Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.
2015SELECT
Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.
2023SELECT-CKD
Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.
2024STEP
Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.
2021STEP
Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.
2022STEP-HFpEF
Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.
2023STEP-HFpEF
Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.
2024SURMOUNT-1
Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.
2022SURMOUNT-2
Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.
2023SURMOUNT-MAINTAIN
Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial
2026SURPASS-2
Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.
2021SURPASS-3
Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.
2021SURPASS-4
Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.
2021SUSTAIN-6
Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.
2016TECOS
Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.
2015UKPDS
Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.
1998VADT
Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.
2009VERIFY
Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.
2019Neurology
44 trialsAcT
Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.
2022ANNEXA-4
Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.
2019ATACH-II
Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.
2016ATTRACTION
Efficacy and safety of tirofiban after successful endovascular reperfusion in acute ischaemic stroke (ATTRACTION) in China: a multicentre, double-blind, randomised controlled trial
2026CENTAUR
AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.
2020CHANCE
Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.
2013CLARITY
Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.
2010CLARITY-AD
Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.
2022CRYSTAL-AF
Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.
2014DAWN
Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.
2017DEFUSE-2
Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.
2012DEFUSE-3
Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.
2018ECASS-3
IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.
2008EMERGE
EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.
2022EMPOWER
MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.
2017ENCHANTED
Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.
2016ESCAPE
Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.
2015EVOLVE-1
Fremanezumab anti-CGRP antibody reduced migraine days in episodic and chronic migraine prevention.
2018EXTEND
IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.
2019EXTEND-IA
Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.
2015FREEDOMS
Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.
2010INTERACT2
Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.
2013IST-3
IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.
2012MR CLEAN
Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.
2015NINDS
IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.
1995OPERA-1
Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.
2017ORATORIO
Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.
2017PHOENIX
Phase 3 PHOENIX trial showed AMX0035 did not slow ALS progression vs placebo; product was withdrawn.
2024POINT
Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.
2018PROMISE-2
IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.
2020RESILIENT
Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.
2020REVASCAT
Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.
2015SANAD
SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.
2007SOCRATES
Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.
2016SPS3
Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.
2012STRIVE
Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.
2017SUNBEAM
Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.
2019SWIFT-PRIME
Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.
2015THALES
Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.
2020THRACE
Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.
2016TIMELESS
Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.
2024TRAILBLAZER-ALZ
Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.
2023VALOR
Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.
2022WAKE-UP
IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.
2018Pulmonology
28 trialsAMBITION
Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.
2015ASCEND
Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.
2014BOREAS
Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).
2023CAPACITY
Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.
2011CHEST-1
Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.
2013DREAM
Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.
2012ETHOS
Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.
2020FLAME
LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.
2016GRIPHON
Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.
2015IMPACT
Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.
2018INBUILD
Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.
2019INPULSIS-1
Nintedanib in IPF — slowed FVC decline.
2014INPULSIS-2
Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.
2014LIBERTY
Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.
2022MENSA
Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.
2014NAVIGATOR
Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.
2021NOTUS
NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.
2024PATENT-1
Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.
2013POET-COPD
Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.
2011QUEST
Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.
2018SENSCIS
Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.
2019SERAPHIN
Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.
2013SIRIUS
Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.
2014STELLAR
Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.
2023TORCH
Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.
2007TRIBUTE
Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.
2018UPLIFT
Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.
2008WISDOM
Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.
2014Critical Care
33 trials65 trial
Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.
20206S hydroxyethyl
Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.
2012ADRENAL
Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.
2018ANDROMEDA-SHOCK
Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.
2019APROCCHSS
Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.
2018ARDSnet
Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.
2000ARISE
Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.
2014ART
Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.
2017BaSICS
Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.
2021CESAR
ECMO referral in severe respiratory failure — improved 6-month outcomes.
2009CHEST
Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.
2012CORTICUS
Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.
2008CRASH-2
Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.
2010CRASH-3
Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.
2019EOLIA
Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.
2018EPaNIC
Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.
2011NICE-SUGAR
Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.
2009PEPTIC
Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.
2020PLUS
Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.
2022ProCESS
Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.
2014ProMISe
EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.
2015PROSEVA
Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).
2013ROSC
BACKGROUND: Exhaled end-tidal carbon dioxide (EtCO 2 ) trajectory is associated with out-of-hospital cardiac arrest (OHCA) outcomes.
2026ROSE
Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.
2019SAFE
4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.
2004SALT-ED
Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.
2018SNAP
Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority r
2026SOAP-II
Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.
2010SUP-ICU
Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.
2018TARGET
Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.
2018TRICC
Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.
1999TRISS
Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.
2014VASST
Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.
2008Oncology
106 trialsADAURA
Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.
2020ALCYONE
Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.
2018ALEX
Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.
2017APHINITY
Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.
2017ARASENS
Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.
2022ASCENT
Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.
2021AURA3
Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.
2017CALGB
Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.
2017CARTITUDE-1
Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.
2021CARTITUDE-4
Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.
2023CASTOR
Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.
2016CheckMate-067
Nivolumab + ipilimumab vs monotherapy in advanced melanoma — durable long-term OS benefit with combination.
2015CheckMate-067
Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.
2017CheckMate-214
Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.
2018CheckMate-577
Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.
2021CheckMate-649
Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.
2021CheckMate-816
Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.
2022CHOP
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
2026CLEAR
Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.
2021CLEOPATRA
Pertuzumab + trastuzumab + docetaxel in HER2+ metastatic breast cancer — major overall survival benefit.
2012CodeBreaK
Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.
2021COMBI-AD
Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.
2017COMPPARE
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
2026CROSS
Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.
2012CROWN
Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.
2020DESTINY-Breast03
Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.
2022DESTINY-Breast04
T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.
2022ECHELON-1
Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.
2018EMBRACA
Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.
2018EMILIA
T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.
2012EPCORE
Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.
2023EV-302
Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.
2023FLAURA
First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — PFS and OS benefit.
2017FLAURA2
Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.
2023GLP-1
10559 Background: Lung cancer (LC) is the leading cause of cancer-related mortality in the United States.
2026HER2
39 Background: The benefit of adjuvant chemotherapy in premenopausal women with hormone receptor (HR)–positive, HER2-negative early breast cancer remains controversial.
2026HER2
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
2026HER2CLIMB
Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.
2020IDEA
IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.
2018III
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.
2020IMpassion130
Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).
2018IMpower010
Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.
2021JCOG1008
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
2022KarMMa
Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.
2021KATHERINE
T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.
2019KEYNOTE-024
First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.
2016KEYNOTE-054
Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.
2018KEYNOTE-189
First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.
2018KEYNOTE-407
First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.
2018KEYNOTE-426
Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.
2019KEYNOTE-522
Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.
2020KEYNOTE-590
Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.
2021KEYNOTE-826
Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.
2021KRYSTAL-1
Adagrasib produced responses in KRAS G12C-mutated NSCLC and colorectal cancer.
2022LATITUDE
Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.
2017MAGIC
Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.
2006MAGNITUDE
Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.
2022MAIA
Daratumumab plus Rd improved PFS and OS in transplant-ineligible newly diagnosed multiple myeloma.
2019MajesTEC-1
Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.
2022MALDI-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.
2023MINDACT
MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.
2016MONALEESA-2
Ribociclib plus letrozole improved PFS and OS in postmenopausal HR+/HER2- advanced breast cancer.
2016monarchE
Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.
2020MOSAIC
Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.
2004NAPOLI-3
NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.
2023NEMIO
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
2026NETTER-1
177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.
2017NOAH
Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.
2010NOVA
Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.
2016OlympiA
One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.
2021PACIFIC
Durvalumab consolidation after chemoradiation in stage III NSCLC — major PFS and OS benefit.
2017PACIFIC-2
Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.
2024PALOMA-2
Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.
2016PALOMA-3
Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.
2015PAOLA-1
Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.
2019PATHFINDER
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.
2026POLARIX
Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.
2022POSEIDON
Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.
2022PRADA
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”
2026PRIMA
Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.
2019PRODIGE
Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.
2021PROfound
Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.
2020PROFOUND
10541 Background: Early cancer detection reduces morbidity and mortality, but current recommended screening in China misses many lethal cancers.
2026RAPIDO
Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.
2020RELATIVITY-047
Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.
2022RUBY
Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.
2023RxPONDER
Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.
2021SEZ6
Abstract Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms.
2026SOLO-1
Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.
2018STAMPEDE
Multi-arm trial showing docetaxel and abiraterone added to ADT improved survival in metastatic hormone-sensitive prostate cancer.
2017SUCCESSOR-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
2026TAILORx
Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.
2018TITAN
Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.
2019TOPAZ-1
Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.
2022TOURMALINE-MM1
Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.
2016TRACE
102 Background: Gastric cancer, a leading global malignancy with high incidence and mortality, poses a significant public health burden in China.
2026TROPiCS-02
Sacituzumab govitecan improved PFS and OS in pretreated HR+/HER2- metastatic breast cancer.
2022TROPION-Lung01
Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.
2023TXI
10582 Background: Colonoscopy remains the gold standard for preventing colorectal cancer;
2026WGS
202 Background: Ovarian cancer, including fallopian tube and primary peritoneal carcinoma, is often diagnosed at advanced stages.
2026WSG
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.
2005ZUMA-1
Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.
2017ZUMA-7
Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.
2022Infectious Disease
48 trialsACTIV-2
COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.
2021ACTIV-3
Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.
2021ACTT-1
Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.
2020ACTT-2
Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.
2021ASTRAL-1
Sofosbuvir-velpatasvir achieved high SVR12 across HCV genotypes 1-6, establishing pan-genotypic therapy.
2015BNT162b2
Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.
2020C-EDGE
Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.
2015CAPiTA
PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.
2015ChAdOx1
ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.
2021COV-BARRIER
Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.
2021COVACTA
Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.
2021DISCOVER
F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.
2020EMPACTA
Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.
2021ENSEMBLE
Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.
2021EPIC-HR
Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.
2022FLU-IVIG
Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.
2019GISAID
Opposites Attract: no linked HIV transmissions among MSM serodiscordant couples when HIV-positive partner virally suppressed.
2018HALO-Influenza
High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.
2014HPTN-052
Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.
2011HPTN-083
Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.
2021ION-1
Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.
2014iPrEx
Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.
2010MATISSE
Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.
2023MELODY
Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.
2022MERINO
Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.
2018MOVe-OUT
Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.
2022mRNA-1273
Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.
2020Nix-TB
BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.
2020NVX-CoV2373
Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.
2021OFLOTUB
Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.
2014PANORAMIC
Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.
2022PNEUMOSIL
PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to PCV13 for IgG responses in infants.
2020PURPOSE-1
Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.
2024PURPOSE-2
Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.
2024R21
R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.
2023RECOVERY
Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.
2021REMAP-CAP
Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.
2021REMoxTB
4-month moxifloxacin-containing regimens were non-inferior to standard 6-month therapy for drug-susceptible TB only weakly.
2014RENOIR
Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.
2023RTS,S
RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.
2015SMART
Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.
2006STAND
Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.
2021START
Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.
2015STOP-TB
TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.
2011STREAM
9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.
2019TEMPRANO
Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.
2015WHO
WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.
2020ZOE-50
Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.
2016Women’s Health & OB-GYN
23 trialsALPS
Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.
2016ARRIVE
Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.
2018ASPRE
Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.
2017BEAM
Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.
2008C*STAR
Pooled cerclage data informed practice for short cervix; ultrasound-indicated cerclage reduced preterm birth in selected.
2018CD40
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
2026CHAP
Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.
2022CHIPS
Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.
2015FlamingoTRA
PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.
2019GBS3
GBS3: routine antenatal screening vs risk-based did not significantly reduce early-onset neonatal GBS disease.
2024HAPO
HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.
2008HERS
Estrogen plus progestin did not reduce CHD events in women with established coronary heart disease.
1998MAGPIE
Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.
2002MFMU
17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.
2003MOMS
Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.
2011MsFLASH
Escitalopram modestly reduced frequency and severity of menopausal hot flashes vs placebo in non-hormonal trial.
2011PRISM
Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.
2019SKYLIGHT
Fezolinetant NK3 receptor antagonist reduced moderate-severe vasomotor symptoms in menopause vs placebo.
2023STRIDER
Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.
2018Term
Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.
2000VICTORY
TMIST will compare digital breast tomosynthesis vs digital mammography for advanced breast cancer outcomes.
2025WOMAN
Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.
2017Women's
Hormone replacement (estrogen + progestin) in postmenopausal women — increased breast cancer and CVD; stopped early.
2002General Medicine
32 trialsALLHAT-LLT
Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.
2002ASPREE
Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.
2018COMPASS
Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.
2017D2d
Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.
2019DASH
DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.
1997DASH-Sodium
Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.
2001DCCT
Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.
1993EAGLES
Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.
2016HOPE
Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.
2000MEGA
Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.
2006MILES
NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.
2011NELSON
Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.
2020NORDICC
Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.
2022PLCO
PLCO: PSA screening did not reduce prostate cancer mortality; annual CXR did not reduce lung cancer mortality.
2012PolyIran
Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.
2019PREDIMED
Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.
2013PREDIMED-Plus
Energy-reduced Mediterranean diet plus physical activity reduced visceral adiposity and possibly CV outcomes.
2023PROSPER
Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.
2002PROVE-HF
TAME PAD: TAILORed prevention efforts in peripheral arterial disease; multidisciplinary intervention outcomes mixed.
2023PURE
PURE study: high carbohydrate intake associated with higher mortality; total fat with lower mortality globally.
2017SALT
SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.
2021SHEP
Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.
1991SPRINT-MIND
Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.
2019STAREE
STAREE will assess atorvastatin in older adults for disability-free survival; reflects elderly statin question.
2025TIPS
TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.
2021TONE
Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.
1998VITAL
Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.
2019VITAL-Bone
Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.
2022VITAL-DEP
Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.
2020VITAL-Rhythm
Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.
2020WHI
Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.
2006WHISH
Multiple women's health prevention trials informed lifestyle guidance; activity recommendations widely cited.
2017Last 24 hours
2 trialsJCOG1008
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
2022HER2
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
2026Last 7 days
5 trialsAC01
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,
2026ATTRACTION
Efficacy and safety of tirofiban after successful endovascular reperfusion in acute ischaemic stroke (ATTRACTION) in China: a multicentre, double-blind, randomised controlled trial
2026TRACE
102 Background: Gastric cancer, a leading global malignancy with high incidence and mortality, poses a significant public health burden in China.
2026HER2
39 Background: The benefit of adjuvant chemotherapy in premenopausal women with hormone receptor (HR)–positive, HER2-negative early breast cancer remains controversial.
2026WGS
202 Background: Ovarian cancer, including fallopian tube and primary peritoneal carcinoma, is often diagnosed at advanced stages.
2026Last 30 days
15 trialsSNAP
Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority r
2026SUCCESSOR-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
2026SGLT2
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
2026REIMAGINE
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
2026ACHIEVE-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
2026COMPPARE
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
2026PATHFINDER
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.
2026DAPA
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
2026PRADA
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”
2026SEZ6
Abstract Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms.
2026CD40
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
2026CHOP
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
2026TXI
10582 Background: Colonoscopy remains the gold standard for preventing colorectal cancer;
2026GLP-1
10559 Background: Lung cancer (LC) is the leading cause of cancer-related mortality in the United States.
2026PROFOUND
10541 Background: Early cancer detection reduces morbidity and mortality, but current recommended screening in China misses many lethal cancers.
2026Last year
511 trialsNEMIO
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
2026PFA-SHAM
BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.
2026NOTION-3
Impact of Angina on Outcome After Percutaneous Coronary Intervention in Patients Undergoing Transcatheter Aortic Valve Implantation: Insights From the NOTION-3 Trial
2026TRIBUTE
Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.
2018III
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.
2024VICTORY
TMIST will compare digital breast tomosynthesis vs digital mammography for advanced breast cancer outcomes.
2025SKYLIGHT
Fezolinetant NK3 receptor antagonist reduced moderate-severe vasomotor symptoms in menopause vs placebo.
2023MsFLASH
Escitalopram modestly reduced frequency and severity of menopausal hot flashes vs placebo in non-hormonal trial.
2011HERS
Estrogen plus progestin did not reduce CHD events in women with established coronary heart disease.
1998STRIDER
Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.
2018BEAM
Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.
2008MOMS
Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.
2011Term
Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.
2000PRISM
Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.
2019MFMU
17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.
2003FlamingoTRA
PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.
2019PATENT-1
Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.
2013STELLAR
Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.
2023BOREAS
Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).
2023INBUILD
Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.
2019INPULSIS-2
Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.
2014PEPTIC
Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.
2020VITAL-DEP
Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.
2020SURMOUNT-2
Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.
2023C*STAR
Pooled cerclage data informed practice for short cervix; ultrasound-indicated cerclage reduced preterm birth in selected.
2018HAPO
HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.
2008WOMAN
Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.
2017ASPRE
Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.
2017CHAP
Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.
2022CHIPS
Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.
2015MAGPIE
Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.
2002ALPS
Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.
2016CHEST-1
Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.
2013AMBITION
Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.
2015GRIPHON
Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.
2015SERAPHIN
Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.
2013NOTUS
NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.
2024LIBERTY
Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.
2022QUEST
Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.
2018NAVIGATOR
Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.
2021SIRIUS
Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.
2014MENSA
Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.
2014DREAM
Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.
2012SENSCIS
Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.
2019POET-COPD
Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.
2011WISDOM
Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.
2014FLAME
LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.
2016ETHOS
Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.
2020IMPACT
Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.
2018UPLIFT
Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.
2008TORCH
Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.
2007CRASH-3
Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.
2019CRASH-2
Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.
201065 trial
Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.
2020EPaNIC
Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.
2011TARGET
Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.
2018SUP-ICU
Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.
2018NICE-SUGAR
Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.
2009PLUS
Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.
2022BaSICS
Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.
2021SALT-ED
Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.
2018CHEST
Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.
20126S hydroxyethyl
Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.
2012SAFE
4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.
2004EOLIA
Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.
2018ROSE
Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.
2019ART
Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.
2017PROSEVA
Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).
2013ProMISe
EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.
2015ARISE
Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.
2014SOAP-II
Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.
2010VASST
Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.
2008CORTICUS
Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.
2008APROCCHSS
Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.
2018ADRENAL
Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.
2018TRISS
Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.
2014TRICC
Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.
1999PLCO
PLCO: PSA screening did not reduce prostate cancer mortality; annual CXR did not reduce lung cancer mortality.
2012NORDICC
Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.
2022NELSON
Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.
2020MILES
NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.
2011WHISH
Multiple women's health prevention trials informed lifestyle guidance; activity recommendations widely cited.
2017PREDIMED
Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.
2013INTERACT2
Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.
2013FIELD
Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.
2005ROSC
BACKGROUND: Exhaled end-tidal carbon dioxide (EtCO 2 ) trajectory is associated with out-of-hospital cardiac arrest (OHCA) outcomes.
2026WSG
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.
2017SALT
SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.
2021TONE
Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.
1998DASH-Sodium
Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.
2001DASH
DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.
1997STAREE
STAREE will assess atorvastatin in older adults for disability-free survival; reflects elderly statin question.
2025ALLHAT-LLT
Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.
2002PolyIran
Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.
2019TIPS
TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.
2021VITAL-Bone
Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.
2022D2d
Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.
2019WHI
Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.
2006PROVE-HF
TAME PAD: TAILORed prevention efforts in peripheral arterial disease; multidisciplinary intervention outcomes mixed.
2023COMPASS
Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.
2017MEGA
Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.
2006PROSPER
Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.
2002SPRINT-MIND
Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.
2019EAGLES
Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.
2016HOPE
Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.
2000SHEP
Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.
1991PREDIMED-Plus
Energy-reduced Mediterranean diet plus physical activity reduced visceral adiposity and possibly CV outcomes.
2023VITAL-Rhythm
Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.
2020VITAL
Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.
2019SANAD
SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.
2007PROMISE-2
IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.
2020EVOLVE-1
Fremanezumab anti-CGRP antibody reduced migraine days in episodic and chronic migraine prevention.
2018STRIVE
Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.
2017EMPOWER
MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.
2017PHOENIX
Phase 3 PHOENIX trial showed AMX0035 did not slow ALS progression vs placebo; product was withdrawn.
2024CENTAUR
AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.
2020VALOR
Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.
2022SUNBEAM
Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.
2019FREEDOMS
Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.
2010CLARITY
Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.
2010ORATORIO
Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.
2017OPERA-1
Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.
2017EMERGE
EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.
2022TRAILBLAZER-ALZ
Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.
2023CLARITY-AD
Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.
2022ANNEXA-4
Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.
2019DEFUSE-2
Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.
2012CRYSTAL-AF
Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.
2014SPS3
Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.
2012ENCHANTED
Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.
2016ATACH-II
Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.
2016SOCRATES
Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.
2016THALES
Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.
2020CHANCE
Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.
2013POINT
Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.
2018RESILIENT
Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.
2020TIMELESS
Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.
2024AcT
Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.
2022THRACE
Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.
2016SWIFT-PRIME
Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.
2015REVASCAT
Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.
2015EXTEND-IA
Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.
2015ESCAPE
Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.
2015MR CLEAN
Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.
2015IST-3
IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.
2012ECASS-3
IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.
2008MERIT
BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.
2013ACCORD-Lipid
Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.
2010VERIFY
Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.
2019HALO-Influenza
High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.
2014FLAURA2
Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.
2023RELATIVITY-047
Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.
2022CANTATA-SU
Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.
2013EMPULSE
Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.
2022SELECT-CKD
Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.
2024STEP-HFpEF
Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.
2024SCALE
Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.
2015ACCORD-MIND
Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.
2011Look
Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.
2012REWIND-CKD
AWARD-7: dulaglutide preserved eGFR and reduced albuminuria in T2D with moderate to severe CKD.
2018DELIVER
Placeholder twin endocrine entries — see SURPASS series for additional tirzepatide outcomes.
2024ACHIEVE-1
Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.
2025OASIS-1
Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.
2023STEP
Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.
2022DPP
Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.
2002LookAHEAD
Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.
2013GRADE
Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.
2022SURPASS-4
Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.
2021SURPASS-3
Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.
2021SURPASS-2
Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.
2021SURMOUNT-1
Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.
2022DEVOTE
Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.
2017ORIGIN
Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.
2012CARMELINA
Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.
2019CAROLINA
Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.
2019ELIXA
Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.
2015HARMONY
Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.
2018AMPLITUDE-O
Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.
2021PIONEER-6
Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.
2019REWIND
Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.
2019EXAMINE
Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.
2013SAVOR-TIMI
Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.
2013TECOS
Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.
2015ACCORD
Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.
2008VADT
Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.
2009ADVANCE
Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.
2008GISAID
Opposites Attract: no linked HIV transmissions among MSM serodiscordant couples when HIV-positive partner virally suppressed.
2018CAPiTA
PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.
2015PNEUMOSIL
PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to PCV13 for IgG responses in infants.
2020ACTT-2
Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.
2021ACTIV-2
COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.
2021STOP-TB
TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.
2011FLU-IVIG
Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.
2019OFLOTUB
Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.
2014STREAM
9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.
2019Nix-TB
BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.
2020STAND
Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.
2021REMoxTB
4-month moxifloxacin-containing regimens were non-inferior to standard 6-month therapy for drug-susceptible TB only weakly.
2014C-EDGE
Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.
2015ION-1
Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.
2014ASTRAL-1
Sofosbuvir-velpatasvir achieved high SVR12 across HCV genotypes 1-6, establishing pan-genotypic therapy.
2015MERINO
Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.
2018MATISSE
Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.
2023MELODY
Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.
2022RENOIR
Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.
2023ZOE-50
Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.
2016R21
R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.
2023RTS,S
RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.
2015MOVe-OUT
Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.
2022iPrEx
Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.
2010MajesTEC-1
Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.
2022NOAH
Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.
2010PAOLA-1
Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.
2019CLEAR
Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.
2021WOEST
Warfarin + clopidogrel vs triple therapy after PCI in patients on OAC — reduced bleeding without ischemic penalty.
2013ENSEMBLE
Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.
2021ChAdOx1
ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.
2021NVX-CoV2373
Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.
2021ACTIV-3
Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.
2021PANORAMIC
Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.
2022EPIC-HR
Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.
2022COV-BARRIER
Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.
2021EMPACTA
Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.
2021COVACTA
Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.
2021REMAP-CAP
Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.
2021PURPOSE-2
Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.
2024PURPOSE-1
Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.
2024HPTN-083
Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.
2021DISCOVER
F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.
2020SMART
Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.
2006TEMPRANO
Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.
2015START
Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.
2015HPTN-052
Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.
2011MAGIC
Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.
2006CROSS
Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.
2012EPCORE
Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.
2023TOURMALINE-MM1
Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.
2016EMILIA
T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.
2012AURA3
Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.
2017IDEA
IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.
2018X-ACT
Adjuvant capecitabine non-inferior to 5-FU/LV in stage III colon cancer with better tolerability.
2005MOSAIC
Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.
2004CheckMate-067
Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.
2017CheckMate-577
Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.
2021KEYNOTE-590
Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.
2021PALOMA-3
Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.
2015MONALEESA-2
Ribociclib plus letrozole improved PFS and OS in postmenopausal HR+/HER2- advanced breast cancer.
2016PALOMA-2
Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.
2016OlympiA
One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.
2021RAPIDO
Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.
2020PRODIGE
Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.
2021NAPOLI-3
NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.
2023TOPAZ-1
Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.
2022POSEIDON
Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.
2022ALEX
Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.
2017CROWN
Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.
2020TROPION-Lung01
Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.
2023PACIFIC-2
Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.
2024KRYSTAL-1
Adagrasib produced responses in KRAS G12C-mutated NSCLC and colorectal cancer.
2022CodeBreaK
Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.
2021MARIPOSA
Amivantamab plus lazertinib improved PFS vs osimertinib in first-line EGFR-mutated advanced NSCLC.
2023MAGNITUDE
Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.
2022PROfound
Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.
2020NOVA
Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.
2016PRIMA
Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.
2019SOLO-1
Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.
2018EV-302
Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.
2023CheckMate-214
Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.
2018KEYNOTE-426
Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.
2019KEYNOTE-054
Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.
2018COMBI-AD
Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.
2017MAIA
Daratumumab plus Rd improved PFS and OS in transplant-ineligible newly diagnosed multiple myeloma.
2019ADAURA
Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.
2020TRILUMINATE
Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.
2023MITRA-HR
MitraClip plus medical therapy vs medical alone in secondary MR — outcomes differed between COAPT and MITRA-FR cohorts.
2018COLCOT
Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.
2019ECHELON-1
Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.
2018POLARIX
Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.
2022CASTOR
Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.
2016ALCYONE
Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.
2018CARTITUDE-4
Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.
2023CARTITUDE-1
Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.
2021KarMMa
Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.
2021ZUMA-7
Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.
2022ZUMA-1
Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.
2017RUBY
Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.
2023KEYNOTE-826
Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.
2021ARASENS
Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.
2022TITAN
Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.
2019LATITUDE
Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.
2017STAMPEDE
Multi-arm trial showing docetaxel and abiraterone added to ADT improved survival in metastatic hormone-sensitive prostate cancer.
2017IMbrave150
Atezolizumab plus bevacizumab improved OS and PFS vs sorafenib in unresectable hepatocellular carcinoma.
2020CheckMate-649
Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.
2021CALGB
Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.
2017RxPONDER
Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.
2021MINDACT
MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.
2016TAILORx
Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.
2018HER2CLIMB
Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.
2020ASCENT
Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.
2021TROPiCS-02
Sacituzumab govitecan improved PFS and OS in pretreated HR+/HER2- metastatic breast cancer.
2022DESTINY-Breast04
T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.
2022DESTINY-Breast03
Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.
2022monarchE
Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.
2020KEYNOTE-522
Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.
2020CheckMate-816
Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.
2022IMpower010
Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.
2021OPTIC
Amiodarone + beta-blocker vs sotalol vs beta-blocker alone for ICD shock prevention — amiodarone combo most effective.
2006PARTITA
VT ablation after first appropriate ICD shock vs continued medical therapy — reduced death/VT storm.
2022VANISH
Catheter ablation vs escalated antiarrhythmic therapy in recurrent VT — reduced composite of death/VT storm/ICD shocks.
2016MADIT-RIT
High-rate or delayed ICD therapy vs conventional programming — reduced inappropriate shocks and mortality.
2012PERIOP-2
LMWH bridging vs placebo during warfarin interruption in high-risk AF/mechanical valves — no benefit, more bleeding.
2021PAUSE
Standardized DOAC interruption strategy in AF undergoing surgery — low rates of bleeding and thromboembolism.
2019BRIDGE
Bridging anticoagulation vs no bridging during warfarin interruption in AF — no thromboembolism reduction, more bleeding.
2015ENTRUST-AF-PCI
Edoxaban-based dual therapy vs warfarin triple therapy after PCI in AF — non-inferior bleeding endpoint.
2019PIONEER-AF-PCI
Rivaroxaban-based vs warfarin triple therapy after PCI in AF — reduced clinically significant bleeding.
2016RE-DUAL
Dabigatran + P2Y12 inhibitor vs warfarin triple therapy after PCI in AF — less bleeding, non-inferior thromboembolism.
2017MANAGE
Dabigatran in perioperative MI/myocardial injury after non-cardiac surgery — reduced major vascular complications.
2018MATRIX
Radial vs femoral access and bivalirudin vs heparin in ACS — radial reduced major bleeding and net adverse events.
2015RIVAL
Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.
2011EVERESTII
MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.
2011RECOVERY
Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.
2020AVATAR
Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.
2021EARLY-TAVR
Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.
2024SURTAVI
Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.
2017DAPA-MI
Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.
2023EMPACT-MI
Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.
2024LoDoCo2
Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.
2020CANTOS
Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.
2017TIMACS
Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.
2009RITA-3
Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.
2002ISCHEMIA-CKD
Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.
2020BARI
Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.
2009SYNTAX
PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.
2009COMPLETE
Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.
2019DANAMI-3
FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.
2015ECLS-SHOCK
VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.
2023IABP-SHOCK
IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.
2012REVEAL
Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.
2017AFCAPS
Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.
1998VALOR-HCM
Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.
2022SHOCK
Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.
1999CULPRIT-SHOCK
Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.
2017HOST-EXAM
Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.
2021MASTER-DAPT
1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.
2021STOPDAPT-2
1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.
2019TWILIGHT
Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.
2019TRITON-TIMI
Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.
2007PLATO
Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.
2009TIMI
Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.
1999GUSTO-I
Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.
1993ISIS-2
Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.
1988ATLAS
Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.
2012ACTIVE-W
Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.
2006ACTIVE-A
Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.
2009EARLY-AF
Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.
2021STOP-AF
Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.
2021PRAGUE-17
LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.
2020PREVAIL
Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.
2014PROTECT-AF
Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.
2009ATHENA
Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.
2009RACE
Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.
2002AFFIRM
Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.
2002PROMINENT
Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.
2022STRENGTH
Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.
2020ORION-11
Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.
2020ORION-10
Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.
2020AIM-HIGH
Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.
2011HPS2-THRIVE
Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.
2014HPS
Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.
2002TNT
Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.
2005PROVE-IT
High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.
2004WOSCOPS
Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.
1995RADIANCE-HTN
Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.
2018VALUE
Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.
2004INVEST
Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.
2003PATHWAY-2
Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.
2015SYMPLICITY
Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.
2014ACCOMPLISH
Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.
2008ASCOT-BPLA
Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.
2005LIFE
Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.
2002HYVET
Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.
2008ATTR-ACT
Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.
2018EXPLORER-HCM
Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.
2020CHAMPION
Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.
2011DANISH
Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.
2016RAFT
CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.
2010MADIT-CRT
CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.
2009CARE-HF
CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.
2005COMPANION
CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.
2004MADIT-II
Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.
2002SCD-HeFT
ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.
2005A-HeFT
Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.
2004AIRE
Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.
1993SAVE
Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.
1992I-PRESERVE
Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.
2008CHARM-Alternative
Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.
2003Val-HeFT
Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.
2001CONSENSUS
Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.
1987SOLVD
Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.
1991COPERNICUS
Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.
2001CIBIS-II
Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.
1999MERIT-HF
Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.
1999EPHESUS
Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.
2003RALES
Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.
1999TOPCAT
Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.
2014ProCESS
Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.
2014SUSTAIN-6
Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.
2016ATTAIN-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.
2026SURMOUNT-MAINTAIN
Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial
2026DCCT
Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.
1993CAST
Encainide/flecainide vs placebo to suppress PVCs post-MI — increased mortality; pivotal negative trial.
1991Women's
Hormone replacement (estrogen + progestin) in postmenopausal women — increased breast cancer and CVD; stopped early.
2002ARRIVE
Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.
2018ASCEND
Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.
2014INPULSIS-1
Nintedanib in IPF — slowed FVC decline.
2014CAPACITY
Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.
2011ANDROMEDA-SHOCK
Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.
2019CESAR
ECMO referral in severe respiratory failure — improved 6-month outcomes.
2009ARDSnet
Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.
2000NETTER-1
177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.
2017EMBRACA
Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.
2018KATHERINE
T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.
2019APHINITY
Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.
2017CLEOPATRA
Pertuzumab + trastuzumab + docetaxel in HER2+ metastatic breast cancer — major overall survival benefit.
2012IMpassion130
Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).
2018PACIFIC
Durvalumab consolidation after chemoradiation in stage III NSCLC — major PFS and OS benefit.
2017FLAURA
First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — PFS and OS benefit.
2017CheckMate-067
Nivolumab + ipilimumab vs monotherapy in advanced melanoma — durable long-term OS benefit with combination.
2015KEYNOTE-407
First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.
2018KEYNOTE-189
First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.
2018KEYNOTE-024
First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.
2016ASPREE
Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.
2018mRNA-1273
Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.
2020BNT162b2
Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.
2020WHO
WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.
2020ACTT-1
Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.
2020WAKE-UP
IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.
2018EXTEND
IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.
2019DEFUSE-3
Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.
2018DAWN
Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.
2017NINDS
IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.
1995UKPDS
Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.
1998STEP-HFpEF
Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.
2023STEP
Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.
2021FLOW
Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.
2024SELECT
Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.
2023DAPA-CKD
Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.
2020CREDENCE
Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.
2019CANVAS
Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.
2017DECLARE-TIMI
Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.
2018LEADER
Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.
2016EMPA-REG
Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.
2015AUGUSTUS
Antithrombotic strategies in AF + ACS/PCI — apixaban without aspirin reduced bleeding without raising ischemic events.
2019POISE-2
Perioperative aspirin and clonidine in non-cardiac surgery — neither reduced CV events; aspirin increased bleeding.
2014POISE
Perioperative metoprolol in non-cardiac surgery — fewer MIs but more strokes and total deaths.
2008MITRA-FR
MitraClip + medical therapy vs medical therapy alone in HF with secondary MR — no benefit (contrast COAPT).
2018COAPT
MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.
2018Evolut
Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.
2019PARTNER
TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.
2019PARTNER
TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.
2016PARTNER
TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.
2011PEGASUS-TIMI
Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.
2015ISAR-REACT
Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.
2019FAME
FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.
2012FAME
FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.
2009NOBLE
PCI vs CABG in left main CAD — CABG superior on composite endpoint.
2016EXCEL
PCI vs CABG in left main CAD — similar 5-year composite outcomes; controversial 10-year mortality signal.
2016FREEDOM
CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.
2012ORBITA-2
PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.
2023ORBITA
PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.
2017COURAGE
PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.
2007AVERROES
Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.
2011CASTLE-AF
Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.
2018EAST-AFNET
Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.
2020CABANA
Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).
2019ARISTOTLE
Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.
2011ROCKET-AF
Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.
2011RE-LY
Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.
20094S Scandinavian
Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.
1994CLEAR
Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.
2023REDUCE-IT
Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.
2019ODYSSEY
Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.
2018FOURIER
Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.
2017IMPROVE-IT
Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.
2015ALLHAT
First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.
2002STEP
Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.
2021HOPE-3
Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.
2016EMPHASIS-HF
Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.
2011SHIFT
Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.
2010CHARM-Added
Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.
2003FINEARTS-HF
Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.
2024STRONG-HF
High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.
2022VICTORIA
Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.
2020GALACTIC-HF
Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.
2021PIONEER-HF
Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.
2019DELIVER
Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.
2022EMPEROR-Preserved
Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.
2021ONTARGET
Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.
2008STICH
CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — long-term mortality benefit with CABG.
2011RECOVERY
Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.
2021ACCORD-BP
Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.
2010ISCHEMIA
Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.
2020COMPASS
Low-dose rivaroxaban + aspirin vs aspirin alone in stable CAD/PAD — reduced major CV events.
2017PARADIGM-HF
Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.
2014EMPEROR-Reduced
Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.
2020DAPA-HF
Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.
2019SPRINT
Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.
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