For dogs with degenerative mitral valve disease, we add pimobendan when overt or impending congestive heart failure occurs in the face of ACE inhibitor, spironolactone, and amlodipine treatment. According to owners, most dogs with overt signs of advanced heart disease feel better and have improved activity tolerance within a few days of adding pimobendan to existing treatment. The clinical improvement may not correlate with hemodynamic improvement. In these cases, pimobendan may have a central nervous system effect that promotes a feeling of physical and mental well-being in dogs as demonstrated by other phosphodiesterase inhibitors (i.e. propentofylline).

DRUG INTERACTIONS

Pimobendan can be administered safely with diuretics, ACE inhibitors, and digoxin.³ The modest vasodilator action of pimobendan is additive to that produced by ACE inhibitors. However, we have not encountered arterial hypotension or a drop in measured systolic blood pressure in any dog in which pimobendan was added to ACE inhibitor monotherapy. Additive vasodilator action should be expected with nitrates (isosorbide dinitrate or nitroglycerin), amlodipine (Norvasc—Pfizer), or carvedilol (Coreg—GlaxoSmithKline). We have encountered mild clinically evident systemic hypotension in only one dog with advanced degenerative mitral valve disease when pimobendan was added to a combination therapy of an ACE inhibitor and amlodipine. We have not observed overt adverse effects with the combination of pimobendan, an ACE inhibitor (enalapril or benazepril), and spironolactone or furosemide treatment in dogs with congestive heart failure. In fact, improved heart function resulting from pimobendan treatment may permit a small reduction of the furosemide dosage.

Serial Holter recordings in our patients with atrial fibrillation have shown that pimobendan does not seem to markedly attenuate the effects of digoxin on reducing atrioventricular conduction. In boxers and Doberman pinschers with advanced dilated cardiomyopathy that we have treated with pimobendan, digoxin, an ACE inhibitor, and furosemide, the ventricular response rates have usually been below 140 beats/min for more than 85% of the approximate 24-hour Holter recording time. In addition, the combination of pimobendan with amiodarone or mexiletine or both has been well-tolerated in boxers and Doberman pinschers with advanced dilated cardiomyopathy and severe ventricular arrhythmias.

PRECAUTIONS

Pimobendan has not been evaluated in dogs used for breeding, in pregnant or lactating dogs, in dogs younger than 6 months old, or in dogs with congenital heart defects, diabetes mellitus, or other serious metabolic diseases. Clinical findings or adverse effects reported during a field study included polyuria, polydipsia, vomiting, azotemia, inappetence, lethargy, diarrhea, dyspnea, pleural effusion, cough, ascites, heart murmur, weakness and ataxia, and syncope.⁹ Sudden death may also occur.⁹ A dose-related sinus tachycardia can result,⁴ and as with any strong inotropic agent, ventricular tachyarrhythmias may develop or worsen while pimobendan is administered.¹¹ Ventricular tachyarrhythmias are of particular concern in Doberman pinschers and boxers but could occur in any dog with advanced dilated cardiomyopathy. Pimobendan's effect on myocytes—conserved energy demand with small increases in intracellular calcium concentration—may reduce the likelihood of a proarrhythmic effect,¹² but additional studies are warranted.

In our experience in treating patients with advanced dilated cardiomyopathy, pimobendan's durability as a positive inotropic agent in dogs may not be as good as that reported in human studies. Thus, prematurely administering pimobendan to patients with only mild to moderate myocardial failure caused by dilated cardiomyopathy could result in decreased effectiveness later in the course of the disease. For this reason, we recommend initiating pimobendan for patients with advanced cardiomyopathy.

Pimobendan's efficacy in cats has not been reported. Hypertrophic cardiomyopathy is the most common cardiomyopathy in cats, and pimobendan is contraindicated.