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).
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.
Theoretically, pimobendan may increase the rate of intestinal digoxin absorption.10 In our clinical experience, the coadministration of pimobendan with digoxin has neither increased paired serum digoxin concentrations
nor resulted in concentrations within the upper 40th percentile of our reference range. We seldom add digoxin to pimobendan
therapy except in the face of atrial fibrillation in dogs with advanced dilated cardiomyopathy.
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.
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.