Effects of fosinopril on exercise tolerance, symptoms, and clinical outcomes in patients with decompensated heart failure.
The purpose of this prospective, multicenter, randomized, double blind, placebo controlled study was to determine the clinical effects of fosinopril in patients with decompensated or worsening heart failure (HF). Patients >/=18 years with New York Heart Association (NYHA) functional class II-IV HF who had been hospitalized or seen in the ER or outpatient clinic for treatment of worsening or decompensated HF were eligible. Patients had to be on diuretic therapy and have a left ventricular ejection fraction (LVEF) </=35% and a treadmill exercise tolerance test (ETT) duration of </=8 minutes. Randomized patients began 12 weeks of fosinopril 10 mg (or placebo) qAM and were titrated within 4 weeks to fosinopril 20 mg and then to 40 mg (or placebo) qAM (if seated, systolic blood pressure (SBP) >/=90 mm Hg). ETTs (modified Naughton protocol) were performed at weeks 1, 3, 6, and 12. A total of 206 patients (mean age 62 years) were randomized to fosinopril (n=102) or placebo (n=104). Most patients were NYHA functional class III (58%) or IV (30%) at presentation; 145 patients completed 12 weeks of treatment (fosinopril, n=85; placebo, n=60). After adjustment for baseline imbalances and investigator effects, fosinopril-treated patients had a 513 second mean exercise duration at endpoint vs. a 489 second duration in placebo-treated patients (p=0.353). When the analysis was adjusted for the impact of dropouts on ETT time, fosinopril-treated patients had a greater exercise duration than those treated with placebo (p=0.043). Fewer patients in the fosinopril group were discontinued from study medication (p=0.008) or hospitalized (p=0.005) for worsening HF. At endpoint, more patients improved their NYHA Functional Class and fewer had worsened with fosinopril vs. placebo (p=0.018); fosinopril-treated patients showed improvements in dyspnea (p=0.054), fatigue (p=0.052), edema (p=0.012), and paroxysmal nocturnal dyspnea (p=0.003) vs. the placebo group. Once-daily fosinopril had a favorable effect on dropout-adjusted exercise tolerance, reduced the frequency of discontinuations or hospitalizations for worsening HF, improved HF signs and symptoms, and was safe and well tolerated. (c)1999 by CHF, Inc.
Bay Pines VA Medical Center, Bay Pines, FL.
U
U
Shettigar
T
T
Hare
K
K
Gelperin
J P
JP
Ilgenfritz
D
D
Deitchman
M
M
Blumenthal