"Enalapril vs. Hydralazine-Isosorbide Dinitrate in the Treatment of Chronic Congestive Heart Failure". The New England Journal of Medicine. 1991. 325:303–310.
Links to original sources: Wiki Journal Post Full Journal Article
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?
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.
Previously, the Vasodilator–Heart Failure Trial (V-HeFT I) had established that combination therapy of hydralazine and isosorbide dinitrate reduced mortality in patients with mild-to-moderate heart failure on digoxin and diuretics. The second Vasodilator–Heart Failure Trial (V-HeFT II) further investigated whether enalapril would offer additional benefits in comparison to hydralazine and isosorbide dinitrate in a similar patient population.
V-HeFT II randomized 804 men to either enalapril or hydralazine-isosorbide dinitrate and found that 2-year mortality was significantly lower in the enalapril group (18%) than in the hydralazine–isosorbide dinitrate group (25%), with a 28% reduction in mortality. The benefit was mainly due to a decrease in sudden deaths, particularly in patients with less severe symptoms. Notably, the physiological endpoints of increased left ventricular ejection fraction and body oxygen consumption at peak exercise were more improved with the hydralazine-isosorbide dinitrate combination.
As of 1991, post-trial, vasodilator therapy was recommended to be included in standard treatment for heart failure. However, no specific guidelines were drafted from the results of V-HeFT II.
Multicenter, double-blind, parallel-group, randomized, active-control trial.
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
- Enalapril 20 mg daily (n=403) or - Hydralazine 300 mg plus Isosorbide dinitrate 160 mg daily (n=401)
Primary Outcomes - Mortality after two years: significantly lower in the enalapril group (18% vs. 25%; P=0.016)
- 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
- 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
Supported by the Cooperative Studies Program of the Medical Research Service, Department of Veterans Affairs Central Office, Washington, D.C.
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