Converting-enzyme inhibitor therapy for chronic heart failure.

In congestive heart failure, acute administration of the converting enzyme inhibitor captopril leads to a decrease in arterial pressure, systemic vascular resistance, left ventricular filling pressure, and the end-diastolic volumes of both ventricles, as well as to an increase in cardiac index, stroke volume index, right and left ventricular ejection fractions. The mechanism of action appears not only attributable to a decrease in angiotensin II but, possibly, may also be accounted for by central and peripheral sympathicolytic effects diminished degradation of bradykinin and an increase in synthesis of vasoactive prostaglandins. During continued treatment with captopril over three months a further decrease in left ventricular filling pressure and an increase in cardiac output can be observed. While the exercise tolerance is not meaningfully affected at the beginning of treatment, a significant increase may be seen during long-term use. After three months of therapy an increase in the acutely-lowered mean arterial pressure can be noted. As compared with placebo-treated control patients, a more favorable clinical course was seen in those receiving captopril. There does not appear to be a relationship, however, between the initial hemodynamic effects and the clinical response. On combined use of captopril and hydralazine, as compared to treatment with captopril only, there is a greater increase in cardiac output and stroke volume without marked additional fall in pulmonary capillary pressure and a further decrease in systemic arterial pressure, incurred without symptomatic hypotension in the majority of patients. The adverse effect is hypotension which precludes long-term treatment in about 10% of patients. Proteinuria, neutropenia and renal insufficiency occur only rarely, usually in patients who are maintained on daily dosages above 300 mg or who have preexisting renal disease. Skin rashes and taste alterations are more common but are frequently well-tolerated and, generally, do not warrant discontinuation of treatment.