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Veterinary Forum February 2008 (Vol 25, No 2)

Cardiology update: canine heart failure

by Sophia Yin, DVM, MS (Animal Science)

    Drug advertisements and pharmaceutical representatives frequently paint a product picture that seems too good to be true. In the case of pimobendan, a cardiac drug that was recently released on the US market as Vetmedin (Boehringer Ingelheim Vetmedica), the hype appears to be backed by results.

    "Pimobendan is a great drug for congestive heart failure," says Lori Siemens, DVM, DACVIM (Cardiology), from Sacramento, Calif. Craig Maretzki, VMD, MS, DACVIM, an internist at San Francisco Veterinary Specialists, agrees: "I have seen a number of patients that had been near death do well on it."

    Pimobendan is a drug that is useful in the treatment of canine congestive heart failure (CHF) secondary to dilated cardiomyopathy (DCM) and chronic degenerative valvular disease. The drug has a dual mechanism of action: It increases myocardial contractility primarily by increasing troponin C's sensitivity to calcium, and it promotes vasodilation by inhibiting phosphodiesterase (PDE) III. It is the first positive inotrope and vasodilator (inodilator) licensed for use in dogs.

    According to Sonya Gordon, DVM, DVSc, DACVIM, a board-certified cardiologist and assistant professor in the department of small animal clinical sciences at Texas A&M University, College Station, pimobendan already had an established track record when it was considered for US licensure.

    "Pimobendan was developed in the 1980s and has been licensed for use in dogs on an international basis for about 8 years. As a result, a body of literature has already been peer reviewed telling us it is safe, well tolerated and efficacious in dogs with heart failure," Gordon explains.

    Although pimobendan was only recently licensed in the United States, Gordon and her associates at Texas A&M University started using the drug 7 years ago and have treated more than 350 dogs with it. A 1998 report from Britain, published in 2002 in the Journal of Veterinary Internal Medicine,1 demonstrated the drug's effectiveness in Doberman pinschers and cocker spaniels with heart failure attributable to DCM, and this report was enough to catch Gordon's attention.

    "At the time," she says, "I had three patients I was particularly attached to: Jake, a Dalmatian; Digger, a Border collie; and Woody, a Cavalier King Charles spaniel. Jake had DCM, and the other two had chronic valve disease. All three dogs were receiving four to six medications and had end-stage refractory heart failure."

    Gordon says that the owners of all three pets were willing to do anything for their dogs, so she decided to try pimobendan. "We obtained an FDA compassionate release to use the drug and started the dogs on it. When the dogs stabilized, the owners were ecstatic — dogs that were at their end had been rescued by pimobendan."

    Multipronged drug protocol the best

    Initially, Gordon and her associates used the drug on a case-by-case basis when conventional drug therapy failed. As additional studies released from Europe, Japan and the United Kingdom showed the usefulness of pimo­bendan in the treatment of canine heart failure, the cardiologists at Texas A&M decided not to wait for all other treatments to fail but instead to start using it when dogs first presented with heart failure.

    Now Gordon recommends that private practitioners use pimobendan regularly in dogs diagnosed with CHF. "If a dog presents with coughing, and radiographs — or echocardiograms — show an enlarged heart with evidence of pulmonary edema, start furosemide, an angiotensin-converting enzyme inhibitor, such as enalapril [Enacard, Merial], and pimobendan," she advises. "Everything we have learned about treating heart failure in humans says it's better to have a multipronged approach." Pimobendan, enalapril and furosemide all have different effects and, therefore, it is not surprising that the best treatment involves a combination of all three agents, she adds.

    Gordon sees pimobendan as a drug that can help practitioners manage uncomplicated canine heart failure caused by chronic valve disease and DCM. Dogs that do not respond well, become refractory or have complicated presentations may still benefit from referral to a cardiologist.

    Pimobendan is easy to use, requires no extra tests beyond those typically conducted when managing heart failure, reduces the frequency at which the furosemide dose may need to be adjusted and has few side effects.

    "In theory," says Gordon, "since it is an afterload reducer, it could cause hypotension, but because of the positive inotropic effect, this effect is offset." The nonselective PDE inhibition also may help palliate signs of pulmonary hypertension, which is a common complication of heart failure resulting from chronic valve disease.

    Caution against drug misuse

    Because pimobendan is so effective and easy to use, Gordon worries that it will be overused or used inappropriately. "It's really a heart failure medication — one for dogs that are or were sick because of heart disease, that is, unstable or unstable heart failure — and not for dogs with heart murmurs or enlarged hearts that are feeling well." In fact, a study by Chetboul and coworkers2 reported that when used in beagles with mild chronic valve disease and no clinical signs, pimobendan caused increased progression of histologic changes and increased regurgitation fraction.

    But when used appropriately, pimobendan has been shown to significantly increase life span and improve quality of life. "Retrospective evaluation of a cohort of dogs from Texas A&M that received pimobendan and other therapies for heart failure from chronic valve disease demonstrated a median survival of 18 months, with many surviving beyond 2 years," Gordon says.

    Dr. Gordon is a consultant for Boehringer Ingelheim Vetmedica, and 3 years ago, Dr. Maretzki participated in a multicenter study that was part of the FDA approval for pimobendan. Dr. Siemens cited no potential conflict of interest relevant to this article.

    1. Fuentes VL, Corcoran B, French A, et al. A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy. J Vet Intern Med 2002;16(3):1255-1261.

    2. Chetboul V, Lefebvre HP, Sampedrano CC, et al. Comparative adverse cardiac effects of pimobendan and benazepril monotherapy in dogs with mild degenerative mitral valve disease: a prospective, controlled, blinded, and randomized study. J Vet Intern Med 2007;21(4):1742-1753.

    References »

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    Did you know... Dogs with dilated cardiomyopathy (DCM) may show subtle clinical signs in the early stages of the disease.Read More

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