Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group.
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.
Erhardt
L
L
Malmö University Hospital, Sweden.
MacLean
A
A
Ilgenfritz
J
J
Gelperin
K
K
Blumenthal
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005080:Exercise Test / Q000187:drug effects*; D017328:Fosinopril / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011446:Prospective Studies; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D017328:Fosinopril