TREATMENT OF CHRONIC CONGESTIVE HEART-FAILURE WITH CAPTOPRIL, AN ORAL INHIBITOR OF ANGIOTENSIN-CONVERTING ENZYME

The renin-angiotensin system is thought to maintain elevated systemic vascular resistance in heart failure. The hemodynamic effects of captopril (SQ 14225), an oral inhibitor of angiotensin-converting enzyme, were measured in 10 patients with stable congestive heart failure poorly controlled by digitalis and diuretics. At single daily doses of 25 to 150 mg, the cardiac index rose from 1.75±0.18 to 2.27±0.39 (mean ± S.D.) liters per minute per square meter (P<0.001), and pulmonary-wedge pressure fell from 26.5±7.5 to 17.3±6.1 mm Hg (P<0.01). Systemic vascular resistance decreased from 2006±300 to 1393±238 dyne seconds per centimeter (P<0.001), and mean arterial pressure fell from 83.7±7.0 to 70.3±9.9 mm Hg (P<0.001) (mean ± S.D.). Heart rate did not change appreciably. Hemodynamic alterations peaked at 90 minutes and persisted for three to four hours. Control plasma renin activity ranged from 1.1 to 7.3 ng per milliliter per hour and did not correlate with changes in hemodynamic values. Three patients on long-term treatment maintained clinical improvement. Although its mechanism of action has not been completely elucidated, captopril may prove useful in the treatment of chronic congestive heart failure. (N Engl J Med 301:117–121, 1979) VASODILATORS are useful in the treatment of congestive heart failure and act by reducing elevated systemic vascular resistance.1,2 The mechanism by which peripheral-arteriolar vasoconstriction occurs in this clinical setting is incompletely understood. Augmented activity of the sympathetic nervous system has been proposed,3,4 as has enhanced stiffness of the arteriolar wall resulting from local retention of sodium and water.5 Recent studies have also implicated the activity of the renin-angiotensin system.6 7 8 9 Renin released by the kidneys catalyzes the formation of angiotensin I, which is converted to angiotensin II, the active vasoconstrictor, by an angiotensin-converting enzyme found widely in the vascular bed.10 Curtiss. © 1979, Massachusetts Medical Society. All rights reserved.