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Veterinary Forum March 2009 (Vol 26, No 3)

Changing paradigm for CHF care

by Paul Basilio

    ORLANDO, Fla. — Pimobendan (Vetmedin, Boehringer Ingelheim Vetmedica) should be part of a multifaceted therapy program for dogs with congestive heart failure (CHF), according to Mark A. Oyama, DVM, DACVIM (Cardiology), associate professor in the department of clinical studies at the University of Pennsylvania School of Veterinary Medicine.

    "It's a positive inotrope, but its mechanism of action is unique," said Oyama in a session sponsored by Boehringer here at The NAVC Conference.

    The key event that causes the heart to contract and determines the force of contractility is the binding of calcium to the actin-myosin complex. Contractility can be increased by either adding more calcium into a cell or making the actin"myosin complex more sensitive to the calcium already hanging around, Oyama explained.

    "All other traditional treatments we know and love, such as dopamine, dobutamine and digoxin, increase contractility by increasing the amount of calcium," he said. "That works, but it comes at a price. If you add too much calcium to a cell, you can make it electrically unstable, kill the cell and get arrhythmias and adverse effects." Pimobendan binds existing calcium to the actin-myosin complex instead of adding calcium.

    Another benefit of pimobendan is its phosphodiesterase inhibition activity, which causes vasodilation in the periphery. This is good for dogs with heart disease because the preload and afterload are decreased to alleviate stress on the heart and to reduce the incidence of CHF.

    "Some good clinical studies have looked at the effects of pimobendan and provide guidance about how to use the drug in practice. We know that in dogs with mitral valve disease (MVD) or dilated cardiomyopathy (DCM), pimobendan prolongs survival and improves clinical signs," Oyama said.

    Initial trials only recorded the time of survival, Oyama said, and studies that look at the quality of life will be welcomed. "One of the real upsides to pimobendan is that it seems to improve the quality of life for dogs," he added.

    Pimobendan should be considered part of the standard triple therapy for dogs with CHF, Oyama said. "Using pimobendan by itself would be unusual. In symptomatic dogs with CHF, you want them to be on a diuretic, and if they're on a diuretic, you want them on an ACE inhibitor as well as pimobendan," he added.

    Oyama said pimobendan is a relatively low-maintenance drug that does not require specific monitoring, but because it is used often with diuretics and an ace inhibitor, the dog's renal function and heart size should be checked routinely.

    It is important to note that pimobendan is indicated for dogs with symptomatic MVD or DCM. "For most dogs, symptomatic means they have ascites, pleural effusion or pulmonary edema," Oyama said. "In some dogs, symptomatic disease might include fainting or profound exercise intolerance, but most will have radiographic signs or signs that can be found on physical examination."

    All of the studies to date have documented the efficacy of pimobendan only in dogs with symptomatic disease. Pimobendan is not recommended in dogs with early heart disease because no data support that use.

    "When ACE inhibitors first came out, the trend was to say, 'Hey, if it's good for a dog with heart failure, it must be good for a dog before it has heart failure,'" Oyama said. "It turns out that probably is not true. We won't know if it's true with pimobendan until we have well-conducted clinical studies addressing that."

    For more information:

    Oyama MA. How and when to use pimobendan. Presented at: The NAVC Conference. Orlando, Fla.; Jan. 17-21, 2009.

    Rosenthal M. QUEST: prolonged survival seen in canine heart failure patients. Veterinary Forum 2008;25(7):29,35.

    Dr. Oyama has consulted for Boehringer Ingelheim Vetmedica (BIV), serves on the company's speaker bureau and is currently involved in a BIV clinical trial.

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