Controlled trial of captopril in chronic heart failure: A rest and exercise hemodynamic study

Abstract

Although many studies have shown acute hemodynamic improvement in patients with congestive heart failure treated with vasodilating drugs, long-term controlled studies with both hemodynamic and exercise capacity measurements are not available. We studied the converting-enzyme inhibitor captopril in 16 ambulatory patients in New York Heart Association functional class II-IV heart failure who were clinically stable on digoxin and diuretics. The acute response to open-label captopril was quantified by blood pool scintigraphy, right-heart catheterization at rest and during exercise, and measurements of exercise capacity. The patients were then randomized to maintenance therapy with captopril or matching placebo and were restudied after 3 months. The two groups were similar in their clinical characteristics and pretreatment rest and exercise hemodynamic measurements. Both displayed similar acute beneficial responses to captopril at rest, with a mean reduction in left ventricular filling pressure from 24 ± 9 to 14 ± 6 mm Hg (p<0.001) and increases in cardiac index, from 2.1 ± 0.5 to 2.5 ± 0.61/min/m2 (p<0.01), and stroke index, from 25 ± 8 to 34 ± 8 ml/m2 (p<0.001). Directionally similar hemodynamic improvement was noted during exercise. After 3 months, these beneficial hemodynamic changes were sustained only in the patients randomized to captopril. Concomitantly, the captopril patients increased their exercise capacity as measured by the duration of bicycle exercise (9.0 ± 2.2 vs 11.7 ± 1.4 min, p<0.01), maximal work load (360 ± 80 vs 460 ± 50 kpm/min, p<0.005) and oxygen consumption (12.9 ± 2.3 vs 15 ± 1.8 ml/kg/min). The placebo group showed either no change or a worsening over the 3 months compared to their pretreatment measurements. These findings demonstrate that captopril is an effective adjunctive agent for the treatment of chronic heart failure and that it produces long-term hemodynamic improvement together with an increase in exercise capacity.