COMPARATIVE EFFECTS OF LOSARTAN AND ENALAPRIL ON EXERCISE CAPACITY AND CLINICAL STATUS IN PATIENTS WITH HEART-FAILURE

Objectives. This study was designed to determine 1) whether 12-week or al administration of losartan, an angiotensin II receptor antagonist, in patients with heart failure is well tolerated; and 2) whether funct ional capacity and clinical status of patients with heart failure in w hom treatment with an angiotensin-converting enzyme (ACE) inhibitor is replaced with losartan for 12 weeks will remain similar to that noted in patients in whom treatment with an ACE inhibitor is continued. Bac kground. Losartan is a specific, nonpeptide angiotensin II receptor an tagonist. Although specific receptor blockade with losartan has certai n theoretic advantages over nonspecific ACE inhibition, definitive dem onstration of comparable effects ia patients with congestive heart fai lure is lacking. Methods. A double-blind, multicenter, randomized, par allel, enalapril-controlled study was conducted in 116 patients with c ongestive heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction less than or equal t o 45% previously treated with stable doses of ACE inhibitors and diure tic agents, with or without concurrent digitalis and other vasodilator s. After a baseline exercise period, open-label ACE inhibitors were di scontinued, and patients were randomly as signed to 12 weeks of therap y with losartan, 25 mg/day (n = 38); losartan, 50 mg/day (n = 40); or enalapril, 20 mg/day (n = 38). Drug efficacy was evaluated by changes in maximal treadmill exercise time (using a modified Naughton protocol ), 6-min walk test, left ventricular ejection fraction and dyspnea-fat igue index. Safety was measured by the incidence of clinical and labor atory adverse experiences. Results. The treadmill exercise time and th e 6-min walk test did not change significantly after replacement of AC E inhibitor therapy with losartan. Similarly, a significant change was not observed in either the dyspnea-fatigue index or left ventricular ejection fraction at the end of double-blind period relative to baseli ne. Conclusions. Losartan was generally well tolerated and comparable to enalapril in terms of exercise tolerance in this short-term (12-wee k) study of patients with heart failure. The clinical effects of long- term angiotensin II receptor blockade compared with ACE inhibition rem ain to be studied. (C) 1997 by the American College of Cardiology.