Enalapril for congestive heart failure

Abstract

In a randomized, double-blind trial, 253 patients with congestive heart failure (New York Heart Association class IV) received either enalapril (n = 127) or placebo (n = 126) in addition to their existing therapeutic regimens (consisting of digitalis, diuretics, and vasodilators other than angiotensin-converting enzyme inhibitors). The study was discontinued prematurely for ethical reasons because of the much lower mortality among the patients receiving enalapril (n = 50) than among those receiving placebo (n = 68) (p < 0.003). The important reduction in mortality was observed among patients dying from progressive heart failure. Follow-up ranged from 1 day to 20 months (average 188 days). The reduction in mortality was associated with general improvements in the symptoms and signs of left and right ventricular heart failure, reduction of heart size, improvements in New York Heart Association classification, reduction of concurrent cardiovascular medication, and reduction of hospital admissions and days spent in the hospital. The overall withdrawal rate was low, and was comparable in the 2 treatment groups (16%; enalapril, n = 22, placebo, n = 18). Symptomatic hypotension was observed in 17% (n = 21) of the enalapril group vs 0% of the placebo group. Hypotension was the reason for withdrawal of enalapril therapy in 7 patients. After the initial dose of enalapril was reduced to 2.5 mg in high-risk patients, hypotension necessitated withdrawal in only 3.2% of the patients. Hyperkalemia was observed exclusively among patients with concurrent use of potassium-sparing agents. At initiation of therapy, serum creatinine levels increased more frequently in the enalapril group than in the placebo group, but was the reason for withdrawal of treatment in only 3 and 2 patients, respectively. A long-term progressive increase in serum creatinine levels was not observed. Hyponatremia at baseline was associated with an increased risk for mortality in patients receiving placebo, but not in those receiving enalapril. It is concluded that enalapril, added to conventional therapy, reduces morbidity and mortality from severe progressive heart failure.