Short- and long-acting angiotensin-converting enzyme inhibitors: A randomized trial of lisinopril versus captopril in the treatment of congestive heart failure

Document Type

Journal Article

Publication Date



Journal of the American College of Cardiology








A randomized, parallel, double-blind study was performed with lisinopril, a long-acting angiotensin-converting enzyme inhibitor, versus captopril, a shorter-acting angiotensin-converting enzyme inhibitor, in the treatment of congestive heart failure. All patients were in New York Heart Association class II, III or IV and had remained symptomatic despite therapy with digoxin and diuretics. After a 4 to 14 day placebo baseline period, patients were randomized to receive either lisinopril, 5 mg orally once per day (n = 94), or captopril, 12.5 mg orally three times per day (n = 95), in addition to continuation of digoxin and diuretics. The dose of study drug could be doubled at 4 week intervals for a total of 12 weeks of double-blind therapy. The maximal dose was 20 mg once per day of lisinopril or 50 mg three times per day of captopril. The addition of either lisinopril or captopril to a regimen of diuretics or digoxin, or both, caused an increase in exercise duration as assessed on a motorized treadmill. When protocol violators were excluded, patients receiving lisinopril had a statistically greater increase in exercise duration than that of patients receiving captopril. In patients with renal impairment (serum creatinine > 1.6 mg/dl at baseline), lisinopril was superior to captopril in improving exercise duration. Lisinopril, but not captopril, increased left ventricular ejection fraction in patients with moderately to severely (<35%) decreased function (p < 0.05). Improvement in functional capacity and quality of life, as assessed by the Yale Scale dyspnea/fatigue index, was significantly greater for the lisinopril group. Lisinopril and captopril were comparable with respect to the safety profiles. Elevations in blood urea nitrogen, but not creatinine, were more frequent with lisinopril. However, these elevations in blood urea nitrogen were reversible with adjustment of diuretic dosage and were not associated with significant morbidity or discontinuation of angiotensin-converting enzyme inhibitor therapy. © 1989.