Comparison of candesartan, enalapril, and their combination in congestive heart failure: Randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study

Background. We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone and their combination on exercise tolerance, ventricular function, quality of life (QOL), neurohormone levels, and combination in congestive heart failure (CHF). Methods and Results. Seven hundred sixty-eight patients in New York Association functional class (NYHA-FC) II to IV with ejection fraction (EF) <0.40 and a 6-minute walk distance (6MWD) <500 m received either candesartan (4, 8, or 16 mg), candesartan (4 or 8 mg) plus 20 mg or enalapril, or 20 mg of enalapril for 43 weeks. There were no differences among groups with regard to 6MWD, NYHA-FC, or QOL. EF increased (P=NS) more with candesartan-plus-enalpril therapy (0.025 ± 0.004) than with candesartan alone (0.015 ± 0.004) or enalpril alone (0.015 ± 0.005). End-diastolic (EDV) and end-systolic (ESV) volumes increased less with combination therapy (EDV 8 ± 4 mL; ESV 1 ± 4 mL; P<0.01) than with candesartan alone (EDV 27 ± 4 mL; ESV 18 ± 3 mL) or enalapril alone (EDV 23 ± 7 mL; ESV 14 ± 6 mL). Blood pressure decreased with combination therapy (6 ± 1/4 ± 1 mm Hg) compared with candesartan or enalapril along (P<0.05). Aldosterone decreased (P<0.05) with combination therapy (23.2 ± 5.3 pg/mL) at 17 but not 43 weeks compared with candesartan (0.7 ± 7.8 pg/mL) or enalapril (-0.8 ± 11.3 pg/mL). Brain natriuretic peptide decreased with combination therapy (5.8 ± 2.7 pmol/L; P<0.01) compared with candesartan (4.4 ± 3.8 pmol/L) and enalapril alone (4.0 ± 5.0 pmol/L). Conclusions. Candesartan alone was as effective, safe, and tolerable as enalpril. The combination of candesartan and enalapril was more beneficial for preventing left ventricular remodeling than either candesartan or enalapril alone.