Pimobendan: Understanding its cardiac effects in dogs with myocardial disease - Veterinary Medicine
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Pimobendan: Understanding its cardiac effects in dogs with myocardial disease
When used in conjunction with other cardiac drugs, pimobendan, unapproved for use in the United States, may benefit dogs with congestive heart failure secondary to dilated cardiomyopathy or valvular insufficiency.


VETERINARY MEDICINE


USE IN DOGS

As stated above, in some countries outside the United States, pimobendan is indicated in dogs to treat congestive heart failure caused by dilated cardiomyopathy or valvular insufficiency. Treatment is initiated in symptomatic patients that may benefit from positive inotropic action. The dosage range is 0.2 to 0.6 mg/kg daily divided into two doses given 12 hours apart.3 Each capsule should be given about one hour before meals, and the capsules should be given whole (not opened) to enhance intestinal absorption.3 The Vetmedin capsule sizes (1.25, 2.5, and 5 mg) were developed based on human dosage requirements. As is typical for many drugs, the dosage requirements for pimobendan in dogs are higher than those required in people. As such, the relatively small capsule sizes are inconvenient to administer to large dogs and contribute to the treatment cost.

Advanced dilated cardiomyopathy

Pimobendan's strongest indication is to treat advanced dilated cardiomyopathy. Patients with advanced dilated cardiomyopathy have poor left ventricular systolic function and reduced ejection fraction. They are subject to increased afterload as a result of dilation of the left ventricle with inadequate wall hypertrophy and arteriolar constriction (caused by activation of the renin-angiotensin-aldosterone system and increased plasma norepinephrine concentrations). This increased afterload negatively affects stroke volume and ejection fraction. Through phosphodiesterase III and V inhibition, pimobendan promotes both arteriolar and venous dilation, reducing afterload and preload, respectively. However, pimobendan's myocardial phosphodiesterase inhibition is probably attenuated in the face of chronic, advanced dilated cardiomyopathy due to beta-receptor downregulation.2

We administer pimobendan in dogs with cardiomyopathy in the face of overt or impending congestive heart failure. Clinical findings consistent with impending congestive heart failure include a gallop heart sound, atrial fibrillation, and nocturnal dyspnea. Pulmonary vein distention on radiographic and echocardiographic examination is also consistent with impending congestive heart failure. Additional echocardiographic changes include increased pulmonary vein flow velocity and increased transmitral diastolic blood flow velocity during the early, rapid-filling phase of diastole. In our experience, pimobendan's positive inotropic effect in dogs with dilated cardiomyopathy is usually demonstrable by echocardiography within one week of initiating treatment.

Mitral valve disease

Patients with myxomatous mitral valve degeneration have good contractility as assessed by echocardiography, even when the left heart is severely dilated. Thus, the inotropic action of pimobendan would seem to be of little value. However, the vasodilator action may contribute to preload and afterload reduction. For 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 the 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, at the University of Georgia Veterinary Teaching Hospital 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 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, ace inhibitor (enalapril or benazepril), spironolactone, and furosemide treatment in dogs with congestive heart failure. In fact, improved heart function resulting from pimobendan treatment may permit a small reduction of furosemide dosage. Concurrent use of pimobendan with a beta-blocker or calcium channel blocker may attenuate the positive inotropic action of pimobendan.


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