Effectiveness of carvedilol alone versus carvedilol + pimobendan for severe congestive heart failure ∗

Pimobendan is a new inotropic agent with phosphodiesterase-inhibiting and calcium-sensitizing effects that increase contractility with minimal increase in oxygen consumption.1‐5 We hypothesized that short-term administration of pimobendan in the early phase of b-blocker therapy would be beneficial in alleviating exacerbation of congestive heart failure (CHF) resulting in withdrawal for patients with severe CHF. The present study investigated the effects of short-term coadministration of pimobendan during introduction of carvedilol therapy on the clinical outcome, left ventricular contractile function, and neurohormone and cytokine levels compared with conventional carvedilol therapy in a randomized fashion in patients with severe CHF. ••• For the present study patients with New York Heart Association (NYHA) class III/IV symptomatic CHF who had multiple episodes of decompensated heart failure and a left ventricular ejection fraction of ,40% on radionuclide ventriculography or contrast ventriculography were enrolled. They were treated with conventional medical treatment including digitalis glycosides, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. Exclusion criteria included a heart rate of ,50 beats/min, systolic blood pressure of ,90 mm Hg, significant bradyarrhythmias or atrioventricular block, serum creatinine of .3.0 mg/dl, and the presence of stenotic valvular heart disease, alcohol abuse, active myocarditis, or hypertrophic obstructive cardiomyopathy. Plasma creatinine phosphokinase level determination and scintigraphic assessment were performed to exclude myocarditis in the absence of biopsy samples. The study protocol was approved by an institutional review committee, and informed consent was obtained from all patients who participated in the study.