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 = 0.101 by ANCOVA and 0.010 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.