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Safety and tolerability of pimobendan in cats with cardiomyopathy

Ward JL, Kussin EZ, Tropf MA, Tou SP, DeFrancesco TC, Keene BW. Retrospective evaluation of the safety and tolerability of pimobendan in cats with obstructive vs nonobstructive cardiomyopathy. J Vet Intern Med. 2020.

Hypertrophic cardiomyopathy (HCM) is the most common cause of heart disease in cats, and is a disease of diastolic dysfunction. Pimobendan is a positive inotrope that increases cardiac contractility, and is used as a mainstay of therapy in dogs with mitral valve disease or dilated cardiomyopathy (both conditions of systolic dysfunction). As such, pimobendan is not routinely used in cats due to the possible detrimental effects (especially in cats with left ventricular outflow obstruction) and the lack of perceived benefit. However, several authors have suggested the use of pimobendan in cats with HCM to increase lusitropy, vasodilation, and atrial function, as well as the possibility that cats with HCM may have a degree of reduced systolic function. Published data on pimobendan in cats is lacking, and while some cardiologists utilize it in all cats with HCM, there remains a concern that in the specific subset of cats with obstructive cardiomyopathy (HOCM) pimobendan will worsen prognosis, however this has not been proven.

The purpose of this study was to describe the safety and tolerability of pimobendan administered to cats with cardiomyopathy and congestive heart failure (CHF), and specifically to investigate for a difference in cats with and without outflow tract obstruction (LVOTO). It was designed as a retrospective cohort study of cats presenting to two veterinary hospitals from 2004 to 2019.

Inclusion criteria were all cats who received at least one dose of pimobendan for the treatment of CHF during the study period. Cats were excluded if they did not have an echocardiogram, if they had congenital heart disease, or if they were diagnosed with high-output heart failure secondary to severe anemia. Signalment, hematologic, and biochemical data were recorded for all cats enrolled, as were concurrent medications and the presence of events that may have precipitated CHF. Manifestations of CHF (ie pulmonary edema, pleural effusion, etc) were also recorded.

Cardiac disease was characterized based on the ACVIM criteria. Standard echocardiographic measurements were recorded. Dynamic LVOTO was defined as turbulent flow on color Doppler in the LV outflow tract and a late-peaking continuous wave Doppler velocity > 1.9 m/s, with or without systolic anterior motion of the mitral valve, as well as the presence of midventricular obstruction. RVOTO was not recorded. Follow up visits, communication logs and medical records were analyzed. Survival times were analyzed. Death was considered cardiogenic if it was due to CHF, feline aortic thromboembolism (FATE), or if cats died at home with no obvious cause.

Two hundred sixty cats were enrolled with a median age of 10 years; 187 were male and 73 female. Two hundred twenty cats had an HCM phenotype (85%). Across all phenotypes, 57 cats (21.9%) were obstructive. 56 (98.2%) of these cats had HCM, one cat was of nonspecific phenotype. No dilated or restrictive cardiomyopathy cases had evidence of obstruction. There were no significant demographic or laboratory differences between obstructive and non-obstructive groups. There was also no difference in drug use and inciting events between groups.

Pimobendan was prescribed a median of 0 days after diagnosis of CHF (range 0-2385 days). The most common dose was 1.25mg q12h PO (0.56mg/kg/day). Dose was escalated in 37.6% of cats. There was no difference in dose between obstructive and non-obstructive groups. Pimobendan was administered for a median of 137 days per cat, for a total of 73272 cat-days (201 cat-years) of exposure in the study.

93.5% of cats were administered furosemide. Starting dose and frequency of administration, frequency of dose escalation, timing of escalation, and maximum dose were not different between groups. 27.3% of cats had a dose decrease at some point. The timing, frequency, and extent of decrease also did not differ between groups.

Adverse effects were seen in 55 cats (21%) with most incidences between obstructive and non-obstructive groups. Most events occurred >45 days from initiation of pimobendan, were associated with diet changes or other drug introductions, or were considered unrelated. These events were mild and included hyporexia, anorexia, lethargy, and vomiting. There was no difference in the timing or frequency of adverse effects between groups. Twelve cats experienced adverse effects suspected to be related to pimobendan, this also did not differ between groups. It was discontinued in 4 cats, which also did not differ between groups.

One hundred fifty-two cats (58.5%) died during the study period, of which 96% died of cardiac causes. There was no difference in rate of death or time to death between groups. Median survival time for cats who died was 150 days.

The authors conclude that pimobendan is overall well tolerated in cats, with few significant complications reported and a survival time comparable to previous reports for cats with CHF. They also concluded that there was no difference in complications or survival times in cats with and without obstruction.

This study investigated the effect of pimobendan in cats with cardiomyopathy and CHF, and the investigators did not find any significant adverse effects of change in outcome between cats with and without obstruction. Several limitations to this study were present. While the authors investigated rates of complications, the study was not designed to investigate efficacy, and so it remains unclear if pimobendan has positive effects or is simply neutral. The study was retrospective, leading to inherent limitations in terms of medical records, inclusion, and study design. There was no negative control group, meaning that there was no ability to compare complication rates and survival times to untreated cats. Further work is indicated in a prospective, placebo-controlled manner to determine if pimobendan has positive effects in cats with cardiomyopathy. (MRK)

See also:

Harris SP, Stern JA, Ontiveros ES, et al. Cardiac effects of a single dose of pimobendan in cats with hypertrophic cardiomyopathy; a randomized, placebo-controlled, crossover study. Front Vet Sci. 2019; 6:15.