2025Ex-DHFExercise trainingIn 322 patients with heart failure and preserved ejection fraction, 12 months of supervised endurance and resistance training did not significantly improve a hierarchical composite of death, hospitalisation, peak oxygen uptake, diastolic function and symptoms compared with usual care, although peak oxygen uptake and NYHA class improved.
2024FINEARTS-HFMRAIn 6,001 patients with heart failure and an ejection fraction ≥ 40 %, finerenone reduced worsening-heart-failure events and cardiovascular death compared with placebo.
2024ATTRibute-CMTTR stabiliserIn 632 patients with transthyretin amyloid cardiomyopathy, acoramidis improved a hierarchical composite of death, CV hospitalisation, NT-proBNP and 6-minute walk distance compared with placebo.
2024SEQUOIA-HCMmyosin inhibitorIn 282 patients with symptomatic obstructive HCM, aficamten improved peak oxygen uptake on exercise testing compared with placebo.
2023STEP-HFpEFGLP-1 RAIn 529 patients with HFpEF (EF ≥ 45%) and obesity (BMI ≥ 30) without diabetes, semaglutide 2.4 mg improved heart-failure symptoms (KCCQ) and body weight compared with placebo.
2022DELIVERSGLT2 inhibitorsIn 6,263 patients with heart failure and an ejection fraction > 40 %, dapagliflozin reduced worsening heart failure or cardiovascular death compared with placebo.
2022STRONG-HFGDMT up-titrationIn 1,078 patients recently hospitalised for acute heart failure, rapid up-titration of guideline-directed therapy with close follow-up reduced 180-day death or heart-failure readmission compared with usual care.
2022VALOR-HCMmyosin inhibitorIn 112 patients with obstructive HCM referred for septal reduction therapy, mavacamten reduced the need to proceed with or remain eligible for septal reduction therapy compared with placebo.
2021EMPEROR-PreservedSGLT2 inhibitorsIn 5,988 patients with HFpEF (EF > 40 %), empagliflozin reduced HF hospitalisation or CV death compared with placebo.
2020EMPEROR-ReducedSGLT2 inhibitorsIn 3,730 patients with HFrEF (EF ≤ 40 %), empagliflozin reduced cardiovascular death or heart-failure hospitalisation compared with placebo.
2020EXPLORER-HCMmyosin inhibitorIn 251 patients with symptomatic obstructive HCM (NYHA II-III, LVOT gradient ≥50 mmHg), mavacamten improved the composite of peak VO2 and NYHA functional class compared with placebo.
2020VICTORIAsGC stimulatorIn 5,050 patients with worsening HFrEF (EF < 45%), vericiguat reduced cardiovascular death or first heart-failure hospitalisation compared with placebo.
2019DAPA-HFSGLT2 inhibitorsIn 4,744 patients with HFrEF (with or without diabetes), dapagliflozin reduced worsening HF or CV death versus placebo.
2019PIONEER-HFARNIIn 881 patients hospitalised for acute decompensated HFrEF, in-hospital initiation of sacubitril/valsartan lowered NT-proBNP more than enalapril.
2018ATTR-ACTCardiomyopathyIn 441 patients with transthyretin amyloid cardiomyopathy, tafamidis reduced all-cause mortality and cardiovascular hospitalisation compared with placebo.
2017RESET-HCMExercise in cardiomyopathyIn 136 adults with hypertrophic cardiomyopathy, 16 weeks of moderate-intensity aerobic exercise training produced a small increase in peak oxygen consumption, with no ventricular arrhythmias, compared with usual activity.
2017SMARTEX-HFExercise intensityIn 261 patients with heart failure and reduced ejection fraction, 12 weeks of supervised high-intensity interval training produced no greater reverse remodelling or gain in left ventricular end-diastolic diameter and peak oxygen uptake than moderate continuous training.
2016STICHCABGIn 1,212 patients with ischaemic cardiomyopathy (EF ≤ 35%) and CAD, coronary-artery bypass grafting plus medical therapy reduced 10-year all-cause mortality compared with medical therapy alone.
2014PARADIGM-HFARNIIn 8,442 patients with HFrEF (EF ≤ 0.40), sacubitril/valsartan reduced CV death or hospitalisation for HF compared with enalapril.
2014TOPCATMRAIn 3,445 patients with HFpEF (EF ≥ 45%), spironolactone did not significantly reduce cardiovascular death, aborted cardiac arrest, or heart-failure hospitalisation compared with placebo.
2011EMPHASIS-HFMRAIn 2,737 patients with mild HFrEF (NYHA II, EF ≤ 35 %), eplerenone reduced cardiovascular death or heart-failure hospitalisation compared with placebo.
2010SHIFTIf-channel inhibitorIn 6,558 patients with HFrEF (EF ≤ 35%) in sinus rhythm with heart rate ≥ 70 bpm, ivabradine reduced cardiovascular death or hospitalisation for worsening heart failure compared with placebo.
2009HF-ACTIONExercise trainingIn 2,331 patients with heart failure and reduced ejection fraction, a supervised aerobic exercise-training programme did not significantly reduce all-cause mortality or hospitalisation compared with usual care.
2004A-HeFThydralazine/nitrateIn 1,050 Black patients with NYHA III-IV HFrEF on standard therapy, fixed-dose isosorbide dinitrate plus hydralazine improved a composite of survival, HF hospitalisation and quality of life compared with placebo.
2003CHARMARBIn 7,601 patients with symptomatic chronic heart failure, candesartan reduced cardiovascular death and heart-failure hospitalisation compared with placebo.
2001COPERNICUSbeta-blockerIn 2,289 patients with severe heart failure and EF ≤ 25%, carvedilol reduced all-cause mortality compared with placebo.
1999MERIT-HFBeta-blockadeIn 3,991 patients with HFrEF (EF ≤ 0.40, NYHA II–IV), metoprolol CR/XL reduced all-cause mortality compared with placebo.
1999RALESMRAIn 1,663 patients with severe HFrEF on ACEi, spironolactone 25 mg reduced all-cause mortality compared with placebo.
1991SOLVDACE inhibitorIn 2,569 patients with symptomatic heart failure and EF ≤ 0.35, enalapril reduced all-cause mortality compared with placebo.
1987CONSENSUSRAAS inhibitionIn 253 patients with NYHA IV heart failure, enalapril reduced 6-month mortality versus placebo.