Landmark Trials

RE-LY

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

4S Scandinavian

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

CLEAR

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

REDUCE-IT

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

ODYSSEY

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

FOURIER

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

IMPROVE-IT

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

ALLHAT

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

STEP

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

HOPE-3

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

EMPHASIS-HF

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

SHIFT

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

CHARM-Added

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

FINEARTS-HF

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

STRONG-HF

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

VICTORIA

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

GALACTIC-HF

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

PIONEER-HF

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

DELIVER

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

EMPEROR-Preserved

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

ONTARGET

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

STICH

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

RECOVERY

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

ACCORD-BP

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

ISCHEMIA

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

COMPASS

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

PARADIGM-HF

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

EMPEROR-Reduced

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

DAPA-HF

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

SPRINT

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

CABANA

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

ARISTOTLE

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

ROCKET-AF

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

FlamingoTRA

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

MILES

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

DELIVER

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

IMpower010

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

ADAURA

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

PRAGUE-17

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

PACIFIC

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

SELECT

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

VICTORY

TMIST will compare digital breast tomosynthesis vs digital mammography for advanced breast cancer outcomes.

SKYLIGHT

Fezolinetant NK3 receptor antagonist reduced moderate-severe vasomotor symptoms in menopause vs placebo.

MsFLASH

Escitalopram modestly reduced frequency and severity of menopausal hot flashes vs placebo in non-hormonal trial.

HERS

Estrogen plus progestin did not reduce CHD events in women with established coronary heart disease.

STRIDER

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

BEAM

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

MOMS

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

Term

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

PRISM

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

GBS3

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

MFMU

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

C*STAR

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

HAPO

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

WOMAN

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

ASPRE

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

CHAP

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

CHIPS

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

MAGPIE

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

ALPS

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

CHEST-1

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

PATENT-1

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

AMBITION

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

GRIPHON

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

SERAPHIN

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

STELLAR

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

NOTUS

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

BOREAS

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

LIBERTY

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

QUEST

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

NAVIGATOR

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

SIRIUS

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

MENSA

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

DREAM

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

INBUILD

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

SENSCIS

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

INPULSIS-2

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

POET-COPD

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

WISDOM

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

FLAME

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

TRIBUTE

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

ETHOS

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

IMPACT

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

UPLIFT

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

TORCH

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

CRASH-3

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

CRASH-2

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

65 trial

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

EPaNIC

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

TARGET

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

SUP-ICU

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

PEPTIC

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

NICE-SUGAR

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

PLUS

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

BaSICS

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

SALT-ED

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

CHEST

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

6S hydroxyethyl

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

SAFE

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

EOLIA

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

ROSE

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

ART

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

PROSEVA

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

ProMISe

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

ARISE

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

SOAP-II

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

VASST

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

CORTICUS

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

APROCCHSS

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

ADRENAL

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

TRISS

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

TRICC

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

PLCO

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

NORDICC

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

NELSON

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

VITAL-DEP

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

WHISH

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

PURE

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

SALT

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

TONE

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

DASH-Sodium

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

DASH

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

STAREE

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

ALLHAT-LLT

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

PolyIran

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

TIPS

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

VITAL-Bone

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

D2d

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

WHI

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

PROVE-HF

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

COMPASS

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

MEGA

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

PROSPER

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

SPRINT-MIND

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

EAGLES

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

HOPE

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

SHEP

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

PREDIMED-Plus

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

PREDIMED

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

VITAL-Rhythm

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

VITAL

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

SANAD

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

PROMISE-2

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

EVOLVE-1

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

STRIVE

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

EMPOWER

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

PHOENIX

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

CENTAUR

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

VALOR

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

SUNBEAM

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

FREEDOMS

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

CLARITY

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

ORATORIO

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

OPERA-1

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

EMERGE

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

TRAILBLAZER-ALZ

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

CLARITY-AD

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

ANNEXA-4

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

DEFUSE-2

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

CRYSTAL-AF

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

SPS3

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

ENCHANTED

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

ATACH-II

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

INTERACT2

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

SOCRATES

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

THALES

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

CHANCE

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

POINT

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

RESILIENT

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

TIMELESS

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

AcT

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

THRACE

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

SWIFT-PRIME

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

REVASCAT

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

EXTEND-IA

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

ESCAPE

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

MR CLEAN

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

IST-3

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

ECASS-3

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

MERIT

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

CANTATA-SU

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

EMPULSE

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

SELECT-CKD

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

STEP-HFpEF

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

SCALE

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

ACCORD-MIND

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

Look

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

REWIND-CKD

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

ACHIEVE-1

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

OASIS-1

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

STEP

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

FIELD

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

ACCORD-Lipid

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

DPP

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

LookAHEAD

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

GRADE

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

SURPASS-4

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

SURPASS-3

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

SURPASS-2

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

SURMOUNT-2

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

SURMOUNT-1

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

VERIFY

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

DEVOTE

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

ORIGIN

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

CARMELINA

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

CAROLINA

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

ELIXA

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

HARMONY

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

AMPLITUDE-O

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

PIONEER-6

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

REWIND

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

EXAMINE

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

SAVOR-TIMI

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

TECOS

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

ACCORD

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

VADT

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

ADVANCE

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

GISAID

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

CAPiTA

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

PNEUMOSIL

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

ACTT-2

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

ACTIV-2

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

STOP-TB

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

FLU-IVIG

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

OFLOTUB

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

STREAM

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

Nix-TB

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

STAND

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

REMoxTB

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

C-EDGE

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

ION-1

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

ASTRAL-1

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

MERINO

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

MATISSE

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

MELODY

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

RENOIR

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

ZOE-50

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

HALO-Influenza

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

R21

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

RTS,S

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

ENSEMBLE

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

ChAdOx1

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

NVX-CoV2373

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

ACTIV-3

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

PANORAMIC

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

EPIC-HR

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

MOVe-OUT

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

COV-BARRIER

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

EMPACTA

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

COVACTA

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

REMAP-CAP

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

PURPOSE-2

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

PURPOSE-1

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

HPTN-083

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

DISCOVER

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

SMART

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

TEMPRANO

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

START

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

HPTN-052

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

iPrEx

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

MAGIC

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

CROSS

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

EPCORE

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

MajesTEC-1

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

TOURMALINE-MM1

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

NOAH

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

EMILIA

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

AURA3

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

IDEA

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

X-ACT

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

MOSAIC

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

CheckMate-067

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

CheckMate-577

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

KEYNOTE-590

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

PALOMA-3

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

MONALEESA-2

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

PALOMA-2

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

OlympiA

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

RAPIDO

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

PRODIGE

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

NAPOLI-3

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

TOPAZ-1

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

POSEIDON

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

ALEX

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

CROWN

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

TROPION-Lung01

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

PACIFIC-2

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

KRYSTAL-1

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

CodeBreaK

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

FLAURA2

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

MARIPOSA

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

MAGNITUDE

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

PROfound

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

NOVA

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

PRIMA

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

RELATIVITY-047

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

PAOLA-1

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

SOLO-1

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

EV-302

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

CLEAR

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

CheckMate-214

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

KEYNOTE-426

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

KEYNOTE-054

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

COMBI-AD

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

ECHELON-1

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

POLARIX

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

CASTOR

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

ALCYONE

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

MAIA

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

CARTITUDE-4

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

CARTITUDE-1

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

KarMMa

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

ZUMA-7

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

ZUMA-1

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

RUBY

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

KEYNOTE-826

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

ARASENS

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

TITAN

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

LATITUDE

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

STAMPEDE

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

IMbrave150

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

CheckMate-649

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

CALGB

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

RxPONDER

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

MINDACT

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

TAILORx

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

HER2CLIMB

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

ASCENT

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

TROPiCS-02

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

DESTINY-Breast04

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

DESTINY-Breast03

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

monarchE

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

KEYNOTE-522

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

CheckMate-816

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

OPTIC

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

PARTITA

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

VANISH

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

MADIT-RIT

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

PERIOP-2

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

PAUSE

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

BRIDGE

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

ENTRUST-AF-PCI

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

WOEST

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

PIONEER-AF-PCI

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

RE-DUAL

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

MANAGE

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

MATRIX

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

RIVAL

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

EVERESTII

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

TRILUMINATE

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

MITRA-HR

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

RECOVERY

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

AVATAR

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

EARLY-TAVR

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

SURTAVI

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

DAPA-MI

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

EMPACT-MI

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

LoDoCo2

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

COLCOT

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

CANTOS

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

TIMACS

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

RITA-3

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

ISCHEMIA-CKD

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

BARI

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

SYNTAX

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

COMPLETE

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

DANAMI-3

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

ECLS-SHOCK

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

IABP-SHOCK

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

SHOCK

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

CULPRIT-SHOCK

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

HOST-EXAM

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

MASTER-DAPT

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

STOPDAPT-2

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

TWILIGHT

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

TRITON-TIMI

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

PLATO

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

TIMI

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

GUSTO-I

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

ISIS-2

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

ATLAS

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

ACTIVE-W

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

ACTIVE-A

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

EARLY-AF

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

STOP-AF

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

PREVAIL

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

PROTECT-AF

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

ATHENA

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

RACE

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

AFFIRM

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

PROMINENT

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

STRENGTH

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

ORION-11

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

ORION-10

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

REVEAL

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

AIM-HIGH

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

HPS2-THRIVE

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

HPS

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

TNT

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

PROVE-IT

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

AFCAPS

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

WOSCOPS

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

RADIANCE-HTN

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

VALUE

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

INVEST

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

PATHWAY-2

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

SYMPLICITY

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

ACCOMPLISH

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

ASCOT-BPLA

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

LIFE

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

HYVET

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

ATTR-ACT

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

VALOR-HCM

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

EXPLORER-HCM

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

CHAMPION

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

DANISH

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

RAFT

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

MADIT-CRT

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

CARE-HF

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

COMPANION

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

MADIT-II

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

SCD-HeFT

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

A-HeFT

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

AIRE

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

SAVE

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

I-PRESERVE

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

CHARM-Alternative

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

Val-HeFT

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

CONSENSUS

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

SOLVD

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

COPERNICUS

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

CIBIS-II

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

MERIT-HF

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

EPHESUS

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

RALES

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

TOPCAT

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

DCCT

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

CAST

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

Women's

Hormone replacement (estrogen + progestin) in postmenopausal women — increased breast cancer and CVD; stopped early.

ARRIVE

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

ASCEND

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

INPULSIS-1

Nintedanib in IPF — slowed FVC decline.

CAPACITY

Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.

ANDROMEDA-SHOCK

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

ProCESS

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

CESAR

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

ARDSnet

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

NETTER-1

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

EMBRACA

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

KATHERINE

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

APHINITY

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

CLEOPATRA

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

IMpassion130

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

FLAURA

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

CheckMate-067

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

KEYNOTE-407

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

KEYNOTE-189

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

KEYNOTE-024

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

ASPREE

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

mRNA-1273

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

BNT162b2

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

WHO

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

ACTT-1

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

WAKE-UP

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

EXTEND

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

DEFUSE-3

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

DAWN

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

NINDS

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

UKPDS

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

STEP-HFpEF

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

STEP

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

FLOW

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

DAPA-CKD

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

CREDENCE

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

CANVAS

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

DECLARE-TIMI

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

SUSTAIN-6

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

LEADER

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

EMPA-REG

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

AUGUSTUS

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

POISE-2

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

POISE

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

MITRA-FR

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

COAPT

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

Evolut

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

PARTNER

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

PARTNER

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

PARTNER

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

PEGASUS-TIMI

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

ISAR-REACT

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

FAME

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

FAME

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

NOBLE

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

EXCEL

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

FREEDOM

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

ORBITA-2

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

ORBITA

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

COURAGE

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

AVERROES

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

CASTLE-AF

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

EAST-AFNET

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