Low-dose enoximone improves exercise capacity in chronic heart failure

OBJECTIVES This study was designed to evaluate the effects of low-dose enox imone on exercise capacity. BACKGROUND At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart fai lure patients but also to increase mortality. The effects of lower doses of enoximone on exercise capacity and adverse events have not been evaluated. METHODS This is a prospective, double-blind, placebo-controlled, multicente r trial (nine U.S. centers) conducted in 105 patients with New York Heart A ssociation class II to III, ischemic or nonischemic chronic heart failure ( CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orall y three times a day. Treadmill maximal exercise testing was done at baselin e and after I, 8 and 12 weeks of treatment, using a modified Naughton proto col. Patients were also evaluated for changes in quality of life and for in creased arrhythmias by Holter monitoring. RESULTS By the protocol-specified method of statistical analysis (the last observation carried-forward method), enoximone at 50 mg three times a day i mproved exercise capacity by 117 a at 12 weeks (p = 0.003). Enoximone at 25 mg three times a day also improved exercise capacity at 12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were noted. There were four deaths in the placebo group and 2 and 0 deaths in the enoximone 25 mg three times a day and enoximone 50 mg three times a day groups, respective ly Effects on degree of dyspnea and patient and physician assessments of cl inical status favored the enoximone groups. CONCLUSIONS Twelve weeks of treatment with low-dose enoximone improves exer cise capacity in patients with CHF, without increasing adverse events. (C) 2000 by the American College of Cardiology.