Long-term efficacy and safety of pimobendan in moderate heart failure. A double-blind parallel 6-month comparison with enalapril. The Pimobendan-Enalapril Study Group.

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, 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 Holter 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 hospitalization 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.(ABSTRACT TRUNCATED AT 250 WORDS)