Malmö University Hospital Malmö, Sweden and Bristol-Myers Squibb Pharmaceutical Research Institute Princeton, New Jersey, U.S.A.
revised 29 March 1995; accepted 26 April 1995.
Correspondence. Dr. Leif Erhardt, Dept. of Cardiology. Maimö University Hospital, 20502 Malmö, Sweden

Abstract
This study was a 12-week, double-blind, placebo-controlled, multinational trial of fosinopril in 308 patients with mild to moderately severe heart failure (New York Heart Association [NYHA] functional class IIS 17%, IIM 48%, and III 35%; mean ejection fraction [± SD] 26.5% [±6.9%]; bicycle exercise duration 1 to 11 min). An initial dose of 10 mg once daily was titrated as tolerated to 40 mg once daily. Patients all received diuretic therapy; digoxin was optional. The primary endpoint was maximal bicycle exercise time; a secondary endpoint was occurrence of the following prospectively defined, ordered clinical events indicative of worsening heart failure; death, study discontinuation, hospitalization, emergency room visits, and need for supplemental diuretic.
At study endpoint (last value obtained for each patient), bicycle exercise time increased more with fosinopril (38.1 s) than with placebo (23.5 s) (P=0.10l by ANCOV A and 0.0.10 by prospectively defined dropout-adjusted endpoint analysis). More patients remained free of clinical events indicative of worsening heart failure when treated with fosinopril (89%) than with placebo (75%), and the worst events of fosinopril-treated patients tended to be less severe than those of placebo patients (P=0.001). Analysis of the occurrence of individual clinical events showed that the need for supplemental diuretic was markedly reduced with fosinopril (8% vs 20% of patients, P=0.002), as were hospitalizations (3% vs 12% of patients, P=0.002) and study discontinuations (2% vs 12% of patients, P<0.001) for worsening heart failure; the two groups had similar incidences of death (3% of patients in the fosinopril group vs 2% in the placebo group, P=0.723). In addition, symptoms of dyspnoea (P=0.017), fatigue (P=0.019), and NYHA functional class (P=0.008 improved with fosinopril relative to placebo.
In conclusion, fosinopril, at an initial dose of 10 mg once daily, subsequently titrated as tolerated to 40 mg once daily, increased exercise tolerance and reduced the frequency of clinical events indicative of worsening heart failure.
Key Words: Angiotensin-converting enzyme inhibitor • fosinopril • heart failure