Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot - RESOLVD


RESOLVD compared the efficacy and tolerability of candesartan, enalapril, and their combination in patients with CHF.


The combination of candesartan (an angiotensin II blocker) with enalapril (an ACE inhibitor) would improve exercise performance, ventricular function, quality of life, neurohormones, and NYHA class over either drug alone. A secondary goal was to identify the optimal dose of candesartan for a larger study.

Study Design

Study Design:

Patients Screened: 899
Patients Enrolled: 768
NYHA Class: baseline class III-IV candesartan 38%, combination 34% enalapril 44%
Mean Follow Up: 43 weeks
Mean Patient Age: not reported
Female: 17
Mean Ejection Fraction: Baseline ejection fraction: candesartan 27%, combination 28% enalapril 27%

Patient Populations:

NYHA class II-IV CHF 6-minute walk distance <500 m Ejection fraction <0.40

Primary Endpoints:

Change in 6-minute walk distance, EF, ventricular volumes, neurohormone levels, QOL, and NYHA class at weeks 17-18 and 43 weeks.

Secondary Endpoints:

Combination of adverse effects (renal dysfunction, symptomatic hypotension, or effects causing study medication discontinuation) and tolerability.

Drug/Procedures Used:

candesartan (dose subgroups 4 mg od, 8 mg od, 16 mg od); candesartan and enalapril (dose subgroups - candesartan 4 mg or 8mg od and enalapril 10 mg bid) enalapril (10 mg bid alone)

Principal Findings:

The study was stopped early on the advice of the external Safety and Efficacy Monitoring Committee because of an adverse trend in the combination of mortality plus heart failure hospitalization in the candesartan alone group. In the final analysis, there was no difference with regard to these outcomes between the groups. There were no differences among groups with regard to 6-minute walk distance, NYHA-FC, or QOL. EF increased (P=NS) more with candesartan-plus-enalapril therapy (2.5%) than with candesartan alone (1.5%) or enalapril alone(1.5%). End-diastolic (EDV) and end-systolic (ESV) volumes increased less with combination therapy (EDV 8 mL, ESV 1 mL) than with candesartan alone (EDV 27 mL, ESV 18 mL) or enalapril alone (EDV 23 mL, ESV 14 mL) (p<0.01). Blood pressure decreased with combination therapy (6±1/4±1 mm Hg) compared with candesartan or enalapril alone (p<0.05). Aldosterone decreased (p<0.05) with combination therapy (23.2 pg/mL) at 17 weeks compared with candesartan (0.7 pg/mL) or enalapril (-0.8 pg/mL). There were no differences in aldosterone at 43 weeks. BNP decreased with combination therapy (5.8 pmol/L) compared with candesartan (4.4 pmol/L) and enalapril alone (4.0 pmol/L) (p<0.01).


RESOLVD, the first study to compare an ARB alone (candesartan) with the combination of an ARB plus an ACE-I (enalapril) and an ACE-I alone in CHF patients, demonstrated that candesartan plus enalapril was well tolerated and was most effective in prevention of left ventricular dilatation and suppression of neurohormonal activation. Additionally, the study showed candesartan alone was as effective, safe, and tolerable as enalapril alone. Larger trials of these two drugs are warranted to assess the effects of combination therapy on major clinical outcomes.


Circulation. 1999;100:1056-1064.

Clinical Topics: Heart Failure and Cardiomyopathies, Novel Agents, Acute Heart Failure

Keywords: Enalapril, Benzimidazoles, Heart Failure, Dilatation, Ventricular Function, Blood Pressure, Tetrazoles, Neurotransmitter Agents

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