The objective of this study was to evaluate the hemodynamic and clinical effects of
fosinopril in patients with
heart failure. This was a prospective, multicenter, double-blind, randomized, parallel-group study. Patients 18 to 80 years of age who were receiving
diuretics with a systolic blood pressure (SBP) > or = 90 mm Hg, New York Heart Association (NYHA) functional class II-IV, left ventricular ejection fraction < or = 40%, pulmonary capillary wedge pressure (PCWP) > or = 18 mm Hg, and a cardiac index (CI) < or = 2.6 L/min/m(2) were eligible. A total of 179 patients were randomized to a single, double-blind oral dose of placebo or
fosinopril at 1, 20, or 40 mg, and hemodynamic monitoring was performed for 24 hours postdose; 155 patients with SBP > or = 90 mm Hg were re-randomized to 10 weeks of double-blind
fosinopril at 1, 20, or 40 mg once daily. Hemodynamic monitoring was repeated at the last visit, beginning at 24 hours postdose (trough) and continuing for 12 hours thereafter. Significant decreases in preload (PCWP) and afterload (mean arterial blood pressure [MABP] and systemic vascular resistance [SVR]) were evident 3 to 4 hours after a single dose of
fosinopril at 20 and 40 mg and continuing for up to 8 to 12 hours postdose for PCWP and SVR and for up to 24 hours postdose for MABP (P < or = .05 v placebo and baseline). Sustained decreases in PCWP, MABP, SVR, and heart rate and increases in CI and stroke volume index were observed after 10 weeks of treatment with
fosinopril at 20 and 40 mg once daily (P < or = .05 v 1 mg group for PCWP and MABP at most time points and P < or = .05 v baseline for other parameters at most time points). Dose-related trends toward reduced supplemental
diuretic use (P = .027) and reduced symptoms of
dyspnea (P = .008) were observed with the 20-mg and 40-mg
fosinopril dose groups. Once daily administration of
fosinopril at 20 and 40 mg was safe and well tolerated, provided a sustained beneficial hemodynamic effect, improved left ventricular performance, and reduced symptoms of
dyspnea, resulting in a reduced need for supplemental
diuretic therapy.