Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure

• Autores: Yamir Reina-Doreste
• Localización: JAVMA: Journal of the American Veterinary Medical Association, ISSN-e 0003-1488, Vol. 245, Nº. 5, 2014, págs. 534-539
• Idioma: inglés
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• Resumen

  • Objective—To assess survival time and adverse events related to the administration of pimobendan to cats with congestive heart failure (CHF) secondary to hypertrophic cardiomyopathy (HCM) or hypertrophic obstructive cardiomyopathy (HOCM).

    Design—Retrospective case-control study.

    Animals—27 cats receiving treatment with pimobendan and 27 cats receiving treatment without pimobendan.

    Procedures—Medical records between 2003 and 2013 were reviewed. All cats with HCM or HOCM treated with a regimen that included pimobendan (case cats) were identified. Control cats (cats with CHF treated during the same period with a regimen that did not include pimobendan) were selected by matching to case cats on the basis of age, sex, body weight, type of cardiomyopathy, and manifestation of CHF. Data collected included signalment, physical examination findings, echocardiographic data, serum biochemical values, and survival time from initial diagnosis of CHF. Kaplan-Meier survival curves were constructed and compared by means of a log rank test.

    Results—Cats receiving pimobendan had a significant benefit in survival time. Median survival time of case cats receiving pimobendan was 626 days, whereas median survival time for control cats not receiving pimobendan was 103 days. No significant differences were detected for any other variable.

    Conclusions and Clinical Relevance—The addition of pimobendan to traditional treatment for CHF may provide a substantial clinical benefit in survival time for HCM-affected cats with CHF and possibly HOCM-affected cats with CHF.

    The positive inotropic and vasodilatory drug pimobendan has become part of the standard of care for management of dogs with CHF and is approved by the US FDA Center for Veterinary Medicine for use in dogs with CHF secondary to dilated cardiomyopathy and chronic mitral valve disease.1–7 Short-term use of positive inotropic agents can also aid in resolution of pulmonary edema and CHF of any etiology in humans because of the ability of these agents to promote improved myocardial relaxation, sarcoplasmic reticulum function, blood flow, and venous capacitance.8–10 Short-term and long-term use of positive inotropic agents in patients with diastolic heart failure is less well accepted. One large post hoc analysis revealed improved survival time in humans administered digoxin, an inotropic agent with a number of additional neuroendocrine-modulating properties.11 Additionally, pimobendan administration to dogs with tachycardia-induced cardiomyopathy resulted in improved cardiac function during diastole.12 There is controversy regarding the use of positive inotropes in cats with CHF; however, the use of pimobendan has been reported with positive results on a limited basis.13–15 Hypertrophic cardiomyopathy and HOCM represent 2 of the most common underlying causes of CHF in cats.16,17 Hypertrophic cardiomyopathy and HOCM are primarily characterized by ventricular hypertrophy, dysfunction during diastole, and elevation of left ventricular end-diastolic pressure and left atrial pressure. The pathological elevation of left ventricular end-diastolic pressure and left atrial pressure translates into elevated pulmonary venous pressures and, in the case of CHF, generation of a combination of pulmonary edema and pleural, pericardial, and abdominal effusions. Additional consequences of HCM and HOCM include arrhythmias, sudden death, and thromboembolic disease. One current recommendation for treatment of CHF in cats includes the use of diuretics, angiotensin-converting enzyme inhibitors, and antiplatelet drugs.18 Some cats with HCM have concurrent LVOT obstruction and are thus classified as having HOCM. Obstruction of the LVOT in cats may be secondary to a single cause or a combination of causes. These include dynamic processes such as cranial motion of the mitral valve during systole, asymmetric septal hypertrophy, or a combination of both. Additionally, fixed obstructions (eg, subaortic stenosis) have been identified in cats. Use of positive inotropic agents and afterload reduction is contraindicated in the face of a fixed obstruction of the outflow tract; therefore, pimobendan is not recommended in these patients.18 Obstruction of the LVOT and its diagnosis may be variable in terms of its presence and severity from day to day because it is dependent on a variety of physiologic factors such as adrenergic tone and blood volume.18 Although pimobendan may be considered contraindicated in patients with severe dynamic obstruction, no information exists to suggest whether the other proposed benefits of pimobendan may outweigh the risks in these patients. As such, treatment of cats with HOCM may be variable depending on the attending clinician and severity of obstruction.

    Pimobendan is a positive inotrope and also has other pharmacological actions that include vasodilatory and antiplatelet properties.19–22 The pharmacological action of pimobendan is a result of inhibition of phosphodiesterase-3 and calcium sensitization of cardiomyocytes.23 Despite these actions, the use of pimobendan in cats with CHF has not gained widespread acceptance and is considered by some to be contraindicated in cats with HCM or HOCM. Investigators of recent studies13–15 have described the therapeutic effect and tolerability of pimobendan in cats with CHF and highlighted its safety as well as its suggested benefits.

    We hypothesized that the addition of pimobendan to traditional CHF treatment would provide a benefit in survival time for HCM-affected cats with CHF and HOCM-affected cats with CHF. The purpose of the study reported here was to identify cats treated with a regimen that included pimobendan as well as age-, sex-, and disease-matched control cats treated with a regimen that did not include pimobendan to assess potential benefits in survival time gained with pimobendan treatment and characterize adverse drug effects that may have resulted from a standard dosage regimen of pimobendan.