Effects of Pimobendan on Adverse Cardiac Events and Physical Activities in Patients With Mild to Moderate Chronic Heart Failure

Abstract

The long-term beneficial effects of pimobendan in the treatment of chronic heart failure (CHF) have not been established, so the present trial compared pimobendan (1.25 or 2.5mg twice daily) vs placebo in 306 patients with stable New York Heart Association class IIm or III CHF, and a radionuclide or echocardiographic left ventricular ejection fraction (LVEF) < or =45% despite optimal treatment with conventional therapy, for up to 52 weeks in a double-blind protocol. At the end of the 52 weeks of treatment, combined adverse cardiac events had occurred in 19 patients in the pimobendan group (15.9%) vs 33 patients in the placebo group (26.3%). The cumulative incidence of combined adverse cardiac events was 45% lower (95% confidence interval of hazard ratio: 0.31-0.97, log-rank test: p=0.035) in the pimobendan group than in the placebo group. Death and hospitalization for cardiac causes occurred in 12 patients in the pimobendan group (10.1%), vs 19 patients in the placebo group (15.3%), but without significant difference. Treatment with pimobendan also increased the mean Specific Activity Scale score from 4.39+/-0.12 at baseline to 4.68+/-0.15 at 52 weeks (p<0.05). In conclusion, long-term treatment with pimobendan significantly lowered morbidity and improved the physical activity of patients with mild to moderate CHF.

Effects of Pimobendan for Mitral Valve Regurgitation in Dogs

“…However, in a long-term study, early clinical trial data demonstrated a trend towards increased mortality in patients with chronic moderate heart failure treated with pimobendan [15]. Nevertheless, a recent study found a reduction in the incidence of adverse cardiac events, including worsening of heart failure and decreased functional capacity, without a significant effect on mortality in patients with mild to moderate congestive heart failure [22].…”

“…In human medicine, pimobendan has been reported to be safe and beneficial in patients with congestive heart failure [12,22]. However, in a long-term study, early clinical trial data demonstrated a trend towards increased mortality in patients with chronic moderate heart failure treated with pimobendan [15].…”

Rationale and Design of a Randomized Trial to Assess the Effects of Diuretics in Heart Failure Japanese Multicenter Evaluation of Long- vs Short-Acting Diuretics in Congestive Heart Failure (J-MELODIC)

“…However, the 2-year incidence in Japan will be probably lower than the data shown above based on previous clinical experience. The combined incidence of death and hospitalization for HF in Japanese patients who were treated with standard therapy was reported to be 15% for 1 year (30% for 2 years) in EPOCH 11 and 5% for 6 months (20% for 2-years) in ARCH-J. 12 Therefore, the 2-year incidence was assumed to be 25% for furosemide and the hazard ratio was conservatively set at 0.5.…”

Ca2+-Sensitisers—A Promising Option to Treat Heart Failure?

“…Pimobendan has vasodilating properties mediated by an activation of the Ca 2+ -dependent K + -channels [11]. The oral intake of pimobendan, however, seems to improve morbidity and the physical exercise capacity of heart failure patients, as recently shown in the PICO-(Pimobendan in Congestive Failure)-trial and the EPOCH-study (Effects of Pimobendan on Chronic Heart Failure [13]). However, mortality rate was not reduced.…”