Comparison of Candesartan, Enalapril, and Their Combination in Congestive Heart Failure

TLDR

Congestive heart failure patients with reduced ejection fraction often receive RAAS blockade, but the comparative effects of candesartan, enalapril, or their combination on exercise tolerance, ventricular function, and quality of life are unclear. The study aimed to compare the effects of candesartan, enalapril, and their combination on exercise tolerance, ventricular function, quality of life, neurohormone levels, and tolerability in CHF patients. A randomized trial of 768 NYHA II–IV CHF patients with EF < 0.40 and 6‑minute walk distance < 500 m treated for 43 weeks with candesartan, enalapril, or their combination was conducted. The combination therapy improved left‑ventricular remodeling, reduced blood pressure, aldosterone, and BNP, and increased ejection fraction more than either drug alone, while exercise tolerance, NYHA class, and quality of life were similar across groups, and candesartan alone was as effective and tolerable as enalapril.

Abstract

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 tolerability in congestive heart failure (CHF). Methods and Results —Seven hundred sixty-eight patients in New York Heart Association functional class (NYHA-FC) II to IV with ejection fraction (EF) &lt;0.40 and a 6-minute walk distance (6MWD) &lt;500 m received either candesartan (4, 8, or 16 mg), candesartan (4 or 8 mg) plus 20 mg of 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-enalapril therapy (0.025±0.004) than with candesartan alone (0.015±0.004) or enalapril 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 &lt;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 alone ( P &lt;0.05). Aldosterone decreased ( P &lt;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 &lt;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 enalapril. The combination of candesartan and enalapril was more beneficial for preventing left ventricular remodeling than either candesartan or enalapril alone.