Copyright © 1994 by the European Society of Cardiology.
© 1994 The European Society of Cardiology
Long-term efficacy and safety of Pimobendan in moderate heart failure: A double-blind parallel 6-month comparison with enalapril
FOR THE PIMOBENDAN-ENALAPRIL STUDY GROUP,Sticares Cardiovascular Research Foundation Rotterdam, The Netherlands
Received 7 September 1993; revised 4 March 1994; .
Correspondence: W.J. Remme, MD, PhD, Sticares Cardiovascular Research Foundation, P.O. Box 52006, 3007 LA Rotterdam, The Netherlands.
Abstract
In view of growing scepticism as to the efficacy and safety of agents with predominant phosphodiesterase inhibiting properties in heart failure, the clinical efficacy and safety of pimobendan, a calcium-sensitizing and partially phosphodiesterase-inhibiting compound, was compared with enalapril in 242 patients with mild to moderate heart failure (NYHA classification II-III) despite diuretics and digitalis, and abnormal haemodynamics at baseline. Patients were randomly assigned to either pimobendan (average 10.3 mg. day–1, 1, n=119), or enalapril (average 10.7 mg. day–1, n=123) in a double-blind fashion for 6 months. Forty-two pimobendan and 37 enalapril patients stopped the treatment, five pimobendan and six enalapril due to worsening of failure without death, whereas 13 and eight patients, respectively, died from cardiac disorders (ns). Other reasons for discontinuation and adverse events not leading to discontinuation were also comparable. Although Holier analysis at 14 days, but not at 6 months, indicated increased ventricular extrasystoles in pimobendan patients, these did not lead to serious clinical events. NYHA classification improved similarly in both groups, from 2.51 to 2.16 (pimobendan) and from 2.40 to 2.06 (enalapril). The number of patients needing a change in background therapy or hospitatization did not differ between the two groups. Haemodynamic variables at rest were improved by both compounds after 6 months. In contrast, only enalapril improved haemodynamics during exercise, and reduced the cardiothoracic ratio. The primary endpoint, exercise capacity, increased significantly during the first 3 months by 45 and 53 s, under pimobendan and enalapril, respectively, but, although unchanged thereafter, the improvement was no longer statistically significant at 6 months in either group.
These data indicate that the calcium sensitizer and partial phosphodiesterase inhibitor pimobendan improves clinical status and exercise tolerance during long-term treatment in mild to moderate heart failure. With the doses used in this study, there was no significant difference between pimobendan and enalapril in therapeutic efficacy and, within the limitations of the study, in safety. This suggests that the usefulness of pimobendan as adjunct ive therapy to diuretics and, possibly, to converting enzyme inhibitors in heart failure patients, should be further evaluated.
Key Words: Heart failure • pimobendan • enalapril • calcium-sensitization • phosphodiesterase inhibition • positive • inotropic agents • humans