COMPARISON OF THE EFFECTS OF LOSARTAN AND ENALAPRIL ON CLINICAL STATUS AND EXERCISE PERFORMANCE IN PATIENTS WITH MODERATE OR SEVERE CHRONICHEART-FAILURE

Objectives. This study assessed the feasibility of an efficacy trial c omparing angiotensin-converting enzyme inhibition and angiotensin II r eceptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatm ent with a converting enzyme inhibitor were randomly assigned to recei ve enalapril or losartan. The study was designed to detect any signs o f clinical deterioration during double blind treatment. Background. Lo sartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting e nzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhib ition, demonstration of a comparable therapeutic effect in patients wi th congestive heart failure will require a major effort comparing two active agents. Methods. One hundred sixty-six patients with stable hea rt failure in New York Heart Association functional class III or IV an d an ejection fraction less than or equal to 35% were included in a mu lticenter, double blind, parallel, enalapril-controlled trial. After a 3-week stabilization period with optimal therapy, including digitalis , diuretic drugs and a converting enzyme inhibitor, patients were rand omly assigned to 8 weeks of therapy with losartan, 25 mg/day (n = 52); losartan, 50 mg/day (n = 56); or enalapril, 20 mg/day (n = 58). Patie nts were assessed with frequent clinical and laboratory evaluation and exercise testing. Results. No significant differences between groups in terms of changes in exercise capacity (6-min, walk test), clinical status (dyspnea-fatigue index), neurohumoral activation (norepinephrin e, N-terminal atrial natriuretic factor), laboratory evaluation or inc idence of adverse experience were observed. Conclusions. The results s uggest that losartan and enalapril are of comparable efficacy and tole rability in the short-term treatment of moderate or severe congestive heart failure. A trial designed to compare the efficacy, tolerability and effect on mortality of long-term angiotensin II receptor blockade with converting enzyme inhibition is both feasible and ethically respo nsible.