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CLINICAL STUDIES

Low-dose enoximone improves exercise capacity in chronic heart failure^*

^a Heart Failure Treatment Program, University of Colorado Health Sciences Center, Denver, Colorado, USA

Manuscript received September 14, 1999; revised manuscript received February 11, 2000, accepted March 30, 2000.

Reprint requests and correspondence: Brian D. Lowes, Heart Failure Treatment Program, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, B120, Denver, Colorado 80126
Brian.Lowes{at}uchsc.edu

OBJECTIVES

This study was designed to evaluate the effects of low-dose enoximone on exercise capacity.

BACKGROUND

At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart failure 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, multicenter trial (nine U.S. centers) conducted in 105 patients with New York Heart Association class II to III, ischemic or nonischemic chronic heart failure (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally three times a day. Treadmill maximal exercise testing was done at baseline and after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol. Patients were also evaluated for changes in quality of life and for increased 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 improved exercise capacity by 117 s 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, respectively. Effects on degree of dyspnea and patient and physician assessments of clinical status favored the enoximone groups.

CONCLUSIONS

Twelve weeks of treatment with low-dose enoximone improves exercise capacity in patients with CHF, without increasing adverse events.

Abbreviations and Acronyms   ACEI = angiotensin-converting enzyme inhibitor   AE = adverse event   ANOVA = analysis of variance   CHF = chronic heart failure   LOCF = last observed carry forward   NYHA = New York Heart Association   PDEI = phosphodiesterase inhibitor   PVC = premature ventricular contraction   VT = ventricular tachycardia

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