Andrew Chong, DVM, DVSc, DACVIM (Cardiology)
Pimobendan is one of the most prescribed cardiac medications for canine and feline patients. It is a calcium sensitizing agent and phosphodiesterase 3 inhibitor, resulting in improved contractility (inotropy), vasodilation, as well as greater heart muscle relaxation (lusitropy).
Use in Degenerative Valvular Disease (DVD)
Pimobendan rose to prominence in 2016 following publication of the EPIC study (Boswood et al. 2016). This study evaluated the effect of pimobendan in dogs with cardiomegaly secondary to degenerative valvular disease (DVD) and found that pimobendan delayed the onset of congestive heart failure (CHF) by roughly 15 months. If one follows the inclusion criteria from this study, then only dogs with DVD that have a vertebral heart sum >10.5 and echocardiographic criteria of left-sided cardiomegaly (LA:Ao ≥1.6, LVIDd normalized ≥1.7) should be started on pimobendan. In practice, it is not always possible for owners to perform both diagnostics. While thoracic radiographs are more readily accessible than echocardiography, one should be careful to not place every dog with a VHS >10.5 on pimobendan, as some of these dogs may not meet the criteria to start pimobendan on echocardiography. The ACVIM Consensus Statement suggests that a vertebral heart sum of ≥11.5 may identify stage B2 dogs that would benefit from pimobendan (i.e. will also meet echocardiographic criteria). Is there an issue in putting a dog on pimobendan when it may not meet these criteria? The primary downside is a large financial burden, as pimobendan costs can add up (and may exceed the cost of repeat echocardiography), along with the inconvenience of having to administer medications that might not have been needed. Historically, there have been concerns of an increased risk of arrhythmias with pimobendan use, but this has not been noted in many landmark trials.
Pimobendan is also essential for treatment of dogs with DVD that have developed CHF. While the typical dose of pimobendan is 0.25-0.30 mg/kg twice daily, higher doses of pimobendan have been used by some clinicians for management of refractory heart failure. A study from Suzuki et al. (2011) in dogs with surgically induced mitral regurgitation showed that dogs on double the standard dose of pimobendan (0.50 mg/kg) had a greater reduction in left atrial pressures compared to standard (0.25 mg/kg) dose pimobendan. However, prospective studies showing improved survival outcome with high dose pimobendan are lacking. One retrospective study (abstract only; Ames ACVIM 2013) suggested that there may be a survival benefit in dogs in refractory CHF placed on three times daily pimobendan.
Use in Dilated Cardiomyopathy (DCM)
As dilated cardiomyopathy (DCM) is a disease characterized by reduced contractility, pimobendan is of immense benefit. Prior to its use in DCM patients, patients with DCM and CHF (especially Doberman Pinschers) may only survive for days or weeks with only furosemide +/- an angiotensin converting enzyme inhibitor. With pimobendan, the median survival time improves to months (see O’Grady et al. 2008; Fuentes et al. 2002). This benefit is also seen in dogs with preclinical DCM (see PROTECT study by Summerfield et al. 2012).
Use in Cats with Hypertrophic Cardiomyopathy (HCM)
Compared to pimobendan use in dogs, the evidence for pimobendan use in cats with hypertrophic cardiomyopathy (HCM) is scant. Pimobendan may be theoretically beneficial for HCM cats due to its ability to enhance lusitropy and improve left atrial contractility. There were some warnings that pimobendan should be avoided in cats with hypertrophic obstructive cardiomyopathy (HOCM), as one study reported a cat with HOCM becoming markedly hypotensive following administration (Gordon et al. 2012). However, subsequent studies in cats with HOCM have not reported similar adverse effects, and in fact pimobendan could reduce the degree of obstruction with chronic use (Schober et al. 2021; Oldach et al. 2019). One retrospective case-control study (Reina-Doreste et al. 2014) showed potential survival benefit in cats with HCM and CHF, however, a more recent prospective study (Schober et al. 2021) did not identify a difference in outcomes between pimobendan and placebo treated cats with HCM and CHF. Despite the low level of evidence in the veterinary literature, pimobendan has been used by cardiologists in HCM cats to manage refractory heart failure, while for others it is used alongside furosemide for first time heart failure cats. My preference is to use it as a rescue agent for the following reasons: 1) Low level of evidence of overt benefit 2) Medication administration compliance decreases with each additional medication prescribed and 3) Stress associated with administration of medications may be so detrimental as to outweigh the benefits of the medication itself.
If you have any questions about this blog post or veterinary cardiology, please feel free to email me at [email protected].
Sincerely,
Andrew Chong, DVM, DVSc, DACVIM (Cardiology).
For further reading:
Boswood, A., Haeggstroem, J., Gordon, S. G., Wess, G., Stepien, R. L., Oyama, M. A., ... & Watson, P. (2016). Effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: the EPIC study—a randomized clinical trial. Journal of veterinary internal medicine, 30(6), 1765-1779.
Keene, B. W., Atkins, C. E., Bonagura, J. D., Fox, P. R., Häggström, J., Fuentes, V. L., ... & Uechi, M. (2019). ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. Journal of veterinary internal medicine, 33(3), 1127-1140.
Suzuki, S., Fukushima, R., Ishikawa, T., Hamabe, L., Aytemiz, D., Huai‐Che, H., ... & Tanaka, R. (2011). The effect of pimobendan on left atrial pressure in dogs with mitral valve regurgitation. Journal of veterinary internal medicine, 25(6), 1328-1333.
O'Grady, M. R., Minors, S. L., O'Sullivan, M. L., & Horne, R. (2008). Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy. Journal of Veterinary Internal Medicine, 22(4), 897-904.
Fuentes, V. L., Corcoran, B., French, A., Schober, K. E., Kleemann, R., & Justus, C. (2002). A double‐blind, randomized, placebo‐controlled study of pimobendan in dogs with dilated cardiomyopathy. Journal of Veterinary Internal Medicine, 16(3), 255-261.
Summerfield, N. J., Boswood, A., O'Grady, M. R., Gordon, S. G., Dukes‐McEwan, J., Oyama, M. A., ... & Watson, P. (2012). Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study). Journal of Veterinary Internal Medicine, 26(6), 1337-1349.
Gordon, S. G., Saunders, A. B., Roland, R. M., Winter, R. L., Drourr, L., Achen, S. E., ... & Miller, M. W. (2012). Effect of oral administration of pimobendan in cats with heart failure. Journal of the American Veterinary Medical Association, 241(1), 89-94.
Schober, K. E., Rush, J. E., Luis Fuentes, V., Glaus, T., Summerfield, N. J., Wright, K., ... & Mohren, N. (2021). Effects of pimobendan in cats with hypertrophic cardiomyopathy and recent congestive heart failure: Results of a prospective, double‐blind, randomized, nonpivotal, exploratory field study. Journal of Veterinary Internal Medicine, 35(2), 789-800.
Oldach, M. S., Ueda, Y., Ontiveros, E. S., Fousse, S. L., Harris, S. P., & Stern, J. A. (2019). Cardiac effects of a single dose of pimobendan in cats with hypertrophic cardiomyopathy; a randomized, placebo-controlled, crossover study. Frontiers in Veterinary Science, 6, 15.
Reina-Doreste, Y., Stern, J. A., Keene, B. W., Tou, S. P., Atkins, C. E., DeFrancesco, T. C., ... & Meurs, K. M. (2014). Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure. Journal of the American Veterinary Medical Association, 245(5), 534-539.
