{"id":14933,"date":"2018-06-26T15:01:49","date_gmt":"2018-06-26T15:01:49","guid":{"rendered":"https:\/\/todaysveterinarypractice.com\/?p=14933"},"modified":"2022-02-15T16:21:32","modified_gmt":"2022-02-15T16:21:32","slug":"pimobendan-and-heart-disease","status":"publish","type":"post","link":"https:\/\/navc.sitepreview.app\/todaysveterinarypractice.com\/pharmacology\/pimobendan-and-heart-disease\/","title":{"rendered":"Pimobendan and Heart Disease"},"content":{"rendered":"

Pimobendan is a benzimidazole-pyridazinone derivative, labeled for use in dogs to manage congestive heart failure (CHF) resulting from dilated cardiomyopathy (DCM) or degenerative mitral valve disease (DMVD) in the United States. On the basis of its positive inotropic effects combined with arteriovenous dilation, it is classified as an inodilator.1<\/sup><\/p>\n

In this article, we provide relevant information about the pharmacology of pimobendan based on a review of the literature providing evidence to support its use for a variety of indications. As additional research is published, the indications and recommended uses for pimobendan continue to evolve.<\/p>\n

Formulation and Dosing<\/h2>\n

Pimobendan is available as Vetmedin (vetmedin.com<\/a>) in oblong, half-scored chewable tablets (1.25 mg, 2.5 mg, 5 mg, or 10 mg). Because the stability and efficacy of the drug in suspension are unknown, reformulating as an oral suspension should be avoided. In some countries outside of the United States, an intravenous preparation is available.<\/p>\n

For dogs, the labeled dosage recommendation for pimobendan is 0.25 to 0.3 mg\/kg PO q12h. The total daily dose can be administered in 2 unequal portions by using whole or half tablets.
\nFor initial use, especially if a more rapid onset of action is desired, the tablets should be administered on an empty stomach; however, for more chronic use, they can be administered with food. In dogs and cats, the oral preparation is rapidly absorbed; peak effect occurs within 2 to 4 hours in dogs and 0.9 hours in cats.1,2<\/sup><\/p>\n

Mechanisms of Action<\/h2>\n

Increased Cardiac Contractility<\/h3>\n

The positive inotropic effects of pimobendan are mediated through a combination of 1) increased cyclic adenosine monophosphate mediated by phosphodiesterase III (PDEIII) inhibition, and 2) sensitization of the cardiac contractile apparatus to intracellular calcium. Calcium sensitization results in a positive inotropic effect without increasing myocardial oxygen demand.<\/p>\n

Vasodilation<\/h3>\n

Balanced vasodilatory effects are mediated predominately through PDEIII inhibition in arterial and venous vascular smooth muscle. Additional endothelial-mediated vasodilation mechanisms may also contribute to this action and may be linked to the medication\u2019s beneficial effect in the treatment of pulmonary hypertension.3<\/sup><\/p>\n

Anticoagulation and Other Properties<\/h3>\n

In platelets, PDEIII inhibition mediates antithrombotic properties, leading to reduced platelet aggregation. This effect has been investigated in other pyridazinone-based compounds as well as pimobendan.4<\/sup> In a study of healthy dogs, pimobendan mildly inhibited platelet aggregation but at a concentration well above a clinically relevant dose.5<\/sup> In mice in heart failure, pimobendan reduced some of the adverse cytokine concentrations.6<\/sup><\/p>\n

Indications<\/h2>\n

Pimobendan is used to treat preclinical and clinical DCM and DMVD (TABLE 1, BOX 1<\/strong>).<\/p>\n

BOX 1 Indications<\/div>
The American College of Veterinary Internal Medicine (ACVIM) consensus statement describes 4 stages of heart disease and failure. The ACVIM consensus statement for DMVD outlines a staging system for preclinical (stage B) and clinical (stages C and D) disease.7<\/sup><\/p>\n

Preclinical DCM (Stage B2)<\/strong>
\nThis stage is characterized by systolic dysfunction (dilated left ventricle in systole) that is usually associated with left ventricular dilation in diastole, with or without left atrial enlargement, and with or without supraventricular and ventricular arrhythmias. Abnormalities are identified by screening with echocardiography and electrocardiography (ECG). The primary diagnostic criterion for preclinical DCM is significant systolic left ventricular dysfunction. Therefore, echocardiography is required to establish a diagnosis (see CASE 1<\/strong>).<\/p>\n

Research data from studies of Doberman pinschers8<\/sup> and Irish wolfhounds9<\/sup> with preclinical DCM show that pimobendan use was associated with<\/p>\n