Comparison of Captopril and Enalapril in Patients with Severe Chronic Heart Failure

To evaluate the concept that long duration of action is an advantageous property of angiotensin-converting enzyme inhibitors in the treatment of severe heart failure, we randomly assigned 42 patients to therapy with either a short-acting inhibitor (captopril, 150 mg daily) or a long-acting inhibitor (enalapril, 40 mg daily) for one to three months while concomitant therapy with digoxin and diuretics was kept constant. The treatment groups had similar hemodynamic and clinical characteristics at base-line evaluation and similar initial responses to converting-enzyme inhibition. During long-term therapy, captopril and enalapril produced similar decreases in systemic blood pressure, but the hypotensive effects of enalapril were more prolonged and persistent than those of captopril. Consequently, although the patients in both groups improved hemodynamically and clinically during the study, serious symptomatic hypotension (syncope and near syncope) was seen primarily among those treated with enalapril. Sustained hypotension also probably accounted for the decline in creatinine clearance (P<0.05) and the notable retention of potassium (P<0.05) observed in the patients treated with enalapril but not in those treated with captopril. We conclude that when large, fixed doses of converting-enzyme inhibitors are used in the treatment of patients with severe chronic heart failure, long-acting agents may produce prolonged hypotensive effects that may compromise cerebral and renal function, and thus they may have disadvantages in such cases, as compared with short-acting agents. (N Engl J Med 1986; 315:847–53.), INHIBITION of the angiotensin-converting enzyme is an established approach to the treatment of patients with severe chronic heart failure.¹ Several double-blind, randomized trials have shown that both captopril and enalapril are more effective than placebo in producing both short-term and long-term hemodynamic and clinical improvement.^{2 3 4 5 6 7 8} Little is known, however, about the comparative efficacy and safety of converting-enzyme inhibitors in these patients. As compared with captopril, enalapril has a greater affinity for the converting enzyme and a more prolonged duration of action. It also lacks a sulfhydryl group — a feature that may be responsible for the rash and dysgeusia that…