Author + information
- Received December 1, 1994
- Revision received March 9, 1995
- Accepted March 14, 1995
- Published online August 1, 1995.
- Kenneth Dickstein, MD, PhD1,a,
- Paul Chang, MDa,
- Ronnie Willenheimer, MDb,
- Stig Haunsø, MD, PhDc,
- Jouko Remes, MDd,
- Christian Hall, MD, PhDe and
- John Kjekshus, MD, PhDF
- ↵1Address for correspondence: Dr. Kenneth Dickstein, Cardiology Division, Central Hospital in Rogaland, 4011, Stavanger, Norway
Objectives. This study assessed the feasibility of an efficacy trial comparing angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatment with a converting enzyme inhibitor were randomly assigned to receive enalapril or losartan. The study was designed to detect any signs of clinical deterioration during double-blind treatment.
Background. Losartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting enzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhibition, demonstration of a comparable therapeutic effect in patients with congestive heart failure will require a major effort comparing two active agents.
Methods. One hundred sixty-six patients with stable heart failure in New York Heart Association functional class III or IV and an ejection fraction ≤35% were included in a multicenter, 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 randomly 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). Patients 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 (norepinephrine, N-terminal atrial natriuretic factor), laboratory evaluation or incidence of adverse experience were observed.
Conclusions. The results suggest that losartan and enalapril are of comparable efficacy and tolerability 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 responsible.
☆ This study was supported by a grant from Merck, Sharp and Dohme Research Laboratories, West Point, Pennsylvania.
- Received December 1, 1994.
- Revision received March 9, 1995.
- Accepted March 14, 1995.