Table 1.
Selected main practice-changing heart failure trials
| Trial | Year | Study treatmenta | No. of patients | Age (years)b | Key age-related inclusion criteria |
|---|---|---|---|---|---|
| SOLVD | 1991 | Enalapril | 2569 | 61 | Age <80; EF ≤ 35% |
| DIG (main trial) | 1997 | Digoxin | 6800 | 63 ± 11 | EF ≤45% |
| RALES | 1999 | Spironolactone | 1663 | 65 ± 12 | EF ≤35% |
| CIBIS II | 1999 | Bisoprolol | 2647 | 61 ± 11 | Age 18–80; EF ≤35% |
| ATLAS | 1999 | Low-dose vs. high-dose lisinopril | 3793 | 64 ± 10 | EF ≤30% |
| COPERNICUS | 2001 | Carvedilol | 2289 | 63 ± 12 | EF ≤25% |
| BEST | 2001 | Bucindolol | 2706 | 60 ± 12 | EF ≤35%. |
| EPHESUS | 2001 | Eplerenone | 6632 | 64 ± 11 | EF ≤40% |
| Val-HeFT | 2002 | Valsartan | 5010 | 62 ± 11 ACEi, 67 ± 10 no ACEi | EF ≤40% |
| MADIT II | 2002 | ICD | 1232 | 64 ± 10 | EF ≤30% |
| COMET | 2003 | Carvedilol vs. metoprolol | 3029 | 62 (11–4)c | EF ≤35% |
| CARE HF | 2005 | CRT vs. medical therapy alone | 813 | 66 (59–72) no CRT, 67 (60–73) CRTc | EF ≤35% |
| MADIT-CRT | 2009 | CRT-D vs. ICD | 1820 | 65 ± 11 | EF ≤30% |
| SHIFT | 2010 | Ivabradine | 6558 | 60 ± 11 | EF ≤35% |
| EMPHASIS | 2011 | Eplerenone | 2737 | 69 ± 8 | EF ≤35% |
Selected landmark heart failure trials, mean or median age of population enrolled, and key age-related inclusion criteria representing a potential age-related selection bias.
ACEi, ACE inhibitor; ATLAS, Assessment of Treatment with Lisinopril and Survival study; BEST, Beta-blocker Evaluation of Survival trial; CARE HF, Cardiac Resynchronization-Heart Failure; CIBIS-II, Cardiac Insufficiency Bisoprolol Trial II; COPERNICUS, Carvedilol Prospective Randomized Cumulative Survival Study; COMET, Carvedilol Or Metoprolol European Trial; CRT, cardiac resynchronization therapy; DIG, Digitalis Investigation Group; EMPHASIS, Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure; EPHESUS, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study; ICD, implantable cardioverter defibrillator; MADIT, Multicenter Automatic Defibrillator Implantation Trial; MERIT-HF, Metoprolol Randomized Intervention Trial in Congestive Heart Failure; RALES, Randomized Aldactone Evaluation Study; SHIFT, Systolic Heart failure treatment with the If inhibitor ivabradine Trial; SOLVD, Studies Of Left Ventricular Dysfunction; Val-HeFT, Valsartan Heart Failure Trial.
aVersus placebo if not otherwise specified.
bMean ± SD, if not otherwise specified.
cMedian (interquartile range).