Table 1.
Study Design, Baseline Characteristics, Duration of Follow‐Up, and Major Outcomes of Included Studies
| Randomized Clinical Trial | BEST9 | CHARM‐Added10 | CHARM‐Alternative11 | CORONA12 | EMPHASIS‐HF13 | WARCEF14 | PARADIGM‐HF15 | ATMOSPHERE16 |
|---|---|---|---|---|---|---|---|---|
| Year of publication | 2001 | 2003 | 2003 | 2007 | 2011 | 2012 | 2014 | 2016 |
| Design | ||||||||
| Target population | ACEI treated HF patients | ACEI treated HF patients | ACEI intolerant HF patients | Older, ischemic and stable HF patients | Optimized medical therapy HF patients | Optimized medical therapy HF patients | Enalapril treated HF patients | Optimized medical therapy HF patients |
| Target LVEF (%) | ≤35 | ≤40 | ≤40 | ≤40 | ≤30 (≤35 if QRS >130 ms) | ≤35 | ≤40 | ≤35 |
| Study treatments | Bucindolol vs placebo | Candesartan vs placebo | Candesartan vs placebo | Rosuvastatin vs placebo | Eplerenone vs placebo | Warfarin vs aspirin | Sacubitril‐valsartan vs enalapril | Aliskiren+enalapril vs aliskiren vs enalapril |
| Population | ||||||||
| Total (N) | 2708 | 2548 | 2028 | 5011 | 2737 | 2293 | 8442 | 7016 |
| Age, y | 60 | 64.1 | 66.6 | 73 | 68.7 | 61 | 63.8 | 63.3 |
| Female, % | 22 | 21.3 | 31.9 | 24 | 22.3 | 20 | 21.8 | 21.7 |
| Hypertension, % | 41 | 51.8 | 55.1 | 63 | 66.5 | 59.6 | 70.7 | 61.7 |
| Diabetes mellitus, % | 35.5 | 29.8 | 27 | 29.5 | 31.4 | 31.5 | 34.7 | 27.7 |
| Nonischemic, % | 41.5 | 37.6 | 30.2 | 0 | 31 | 57 | 40 | 44 |
| Atrial fibrillation, % | 11.5 | 46.1 | 74.6 | 23.5 | 30.9 | 3.7 | 36.8 | 40.6 |
| Mean eGFR, mL/min per 1.73 m2 | 65.5±23.2 | 71.5±28 | 71.5±28 | 58±15 | 70.8±21.8 | 68.4±20.5 | 67.6±18.5 | 74±24 |
| NYHA III/IV, % | 100 | 75.9 | 52.4 | 62.9 | 0 | 30.9 | 24.6 | 36.7 |
| LVEF, % | 23 | 28 | 29.9 | 31 | 26.2 | 25.0 | 29.5 | 28.4 |
| Beta‐blockers, % | 50 | 55.5 | 54.5 | 75.2 | 86.7 | 89.9 | 92.5 | 91.7 |
| ACEI/ARB, % | 97.6 | 99.9 | 50 | 91.8 | 93.4 | 98.4 | 100 | 66.6 |
| Mineralocorticoid antagonist, % | 3.5 | 17.2 | 23.8 | 39.2 | 49.8 | 60.4 | 55.3 | 37.1 |
| ICD, % | 3.4 | 3.9 | 3.4 | 2.7 | 15.4 | 18.2 | 14.7 | 14.9 |
| CRT, % | NR | NR | NR | NR | 8.5 | NR | 6.8 | 5.6 |
| Follow‐up, mo | 24 | 41 | 33.7 | 32.8 | 21 | 22.8 | 27 | 36.6 |
| All‐cause death (100 patient/years) | 15.88 | 9.06 | 9.85 | 10.86 | 8.02 | 11.71 | 8.18 | 8.86 |
| Sudden death (100 patient/years) | ··· | 3.65 | 3.35 | 4.69 | 2.84 | 4.07 | 2.97 | ··· |
ACEI indicates angiotensin‐converting‐enzyme inhibitors; ARB, antiotensin‐2 receptor blockers; ATMOSPHERE, Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure; BEST, Beta‐Blocker Evaluation of Survival Trial; CHARM ‐ Added, Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity ‐ Added Trial; CHARM ‐ Alternative, Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity ‐ Alternative Trial; CORONA, Controlled Rosuvastatin Multinational Trial in Heart Failure; CRT, cardiac resynchronization therapy; eGFR, estimated glomerular filtration rate; EMPHASIS‐HF, Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure; HF, heart failure; ICD, implantable cardioverter–defibrillator; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association functional class; NR, not reported; and WARCEF, Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction.