"Enalapril vs. Hydralazine-Isosorbide Dinitrate in the Treatment of Chronic Congestive Heart Failure". The New England Journal of Medicine. 1991. 325:303–310.

Clinical Question

Does enalapril offer a mortality benefit over the combination of hydralazine and isosorbide dinitrate in men with chronic congestive heart failure receiving digoxin and diuretic therapy?

Bottom Line

In men with chronic congestive heart failure on standard therapy with digoxin and diuretics, treatment with enalapril resulted in a significant reduction in 2-year mortality compared with hydralazine and isosorbide dinitrate, mainly due to a reduction in sudden deaths.

Major Points

Guidelines

Design

Multicenter, double-blind, parallel-group, randomized, active-control trial.

Population

Inclusion Criteria
- Men aged 18-75 with chronic heart failure
- Cardiac dysfunction with reduced exercise tolerance (cardiothoracic ratio ≥0.55, left ventricular internal diameter >2.7 cm/m^2 at diastole, or ejection fraction <0.45)

Exclusion Criteria
- Myocardial infarction or cardiac surgery within the last 3 months, limiting angina, significant obstructive valvular or lung disease, other life-limiting comorbidities

Baseline Characteristics
- Average age 61 years, majority with ejection fraction <0.45, 53% had coronary artery disease as primary cause of heart failure

Interventions

- Enalapril 20 mg daily (n=403) or
- Hydralazine 300 mg plus Isosorbide dinitrate 160 mg daily (n=401)

Outcomes

Primary Outcomes
- Mortality after two years: significantly lower in the enalapril group (18% vs. 25%; P=0.016)

Secondary Outcomes
- Overall mortality: tended to be lower in the enalapril group (P=0.08)
- Cause of death: Reduction in sudden deaths, without or with premonitory worsening of cardiac status in the enalapril group

Criticisms

- Lack of a placebo group due to ethical concerns following the results of V-HeFT I
- Results may not be generalizable to women or those with severe heart failure
- The parallel design did not allow for direct testing of any additive effects of combination therapy
- Limited information on quality of life and functional status improvements

Funding

Supported by the Cooperative Studies Program of the Medical Research Service, Department of Veterans Affairs Central Office, Washington, D.C.

Further Reading

N/A