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Pimobendan for cats?: where are we now (early 2021 updated update!)

Traditionally, there has been a concern that pimobendan, a positive inotrope (inodilator), would be contraindicated in the presence of outflow tract obstruction.  Obviously, left ventricular outflow tract obstruction is a big deal in cats because hypertrophic cardiomyopathy is the commonest feline heart disease and many of them exhibit dynamic or fixed obstruction.  To the best of my knowledge this is a theoretical concern based on mechanistic reasoning.

It’s been a few years since this small pilot study was published:

Reina-Doreste Y, Stern JA, Keene BW, Tou SP, Atkins CE, DeFrancesco TC, et al. . Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure. J Am Vet Med Assoc. (2014) 245:534–9. 10.2460/javma.245.5.534

https://pubmed.ncbi.nlm.nih.gov/25148095/

It includes only 27 cats.  However, the results are striking.

‘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’

It has to be noted that only 5/27 of those pimobendan-treated cats had hypertrophic, obstructive CM.

It’s also noteworthy that…

‘1 cat (4%) with LV OTO had an adverse effect. This cat was diagnosed with complex congenital heart disease (mitral valve dysplasia and ventricular septal defect) including systolic anterior motion of the mitral valve, and was reported to experience acute hypotension (systolic blood pressure 60 mmHg) and tachycardia (240 bpm) after a single dose of pimobendan PO’

…especially because there are anecdotal reports of similar cases.

More recently and more specifically we have:

Front Vet Sci. 2019; 6: 15.
Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study
Maureen S. Oldach,1 Yu Ueda,2 Eric S. Ontiveros,2 Samantha L. Fousse,2 Samantha P. Harris,3 and Joshua A. Stern

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369151/

These guys found no evidence of accelerated LV outflow tract velocities with pimobendan.

This broad conclusion is supported by:

J Vet Intern Med 2020 Nov;34(6):2211-2222
Retrospective evaluation of the safety and tolerability of pimobendan in cats with obstructive vs nonobstructive cardiomyopathy
Jessica L Ward, Efrem Z Kussin, Melissa A Tropf, Sandra P Tou, Teresa C DeFrancesco, Bruce W Keene

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694854/

…which is a much more extensive investigation of the potential issue of outflow tract obstruction involving 260 clinical cases of feline CHF of which 57 exhibited outflow tract obstruction.

I’ve sliced and diced the key points here….

‘Pimobendan was most commonly initially prescribed at a dose of 1.25 mg PO q12h per cat, resulting in a median total daily dose of 0.56 mg/kg/day (range 0.12‐1.74 mg/kg/day)

Results:

Acute adverse hemodynamic effects after pimobendan administration were not detected in any cats.

Twelve cats (4.6%), including 11 (5.4%) cats with nonobstructive disease and 1 (2%) cat with obstructive disease, were reported to experience adverse effects considered to be potentially attributable to pimobendan based on patterns of timing and resolution. These adverse effects occurred a median of 10 days (range 1‐40) after pimobendan initiation, and consisted of hyporexia/anorexia (7 cats, 1 of which was also lethargic and 2 of which also had vomiting), vomiting (6 cats, 2 of which also had hyporexia/anorexia), and subclinical hypotension (1 cat).

1.5% of cats had pimobendan therapy discontinued due to adverse effects

Conclusions and Clinical Importance:

Pimobendan is well tolerated in cats with cardiomyopathy and CHF, regardless of the presence of outflow tract obstruction‘

Also very recently published is:

Journal of Veterinary Internal Medicine 
Effects of pimobendan on left atrial transport function in cats
Samantha L. Kochie Karsten E. Schober Jaylyn Rhinehart Randolph L. Winter John D. Bonagura Annie Showers Vedat Yildez

https://onlinelibrary.wiley.com/doi/10.1111/jvim.15976

This study enrolled 22 HCM cats (and 11 in placebo group) and demonstrated modest increases in left auricular appendage flow velocity and late transmitral flow velocity.  

Given that left atrial size and function are important echocardiographic markers of disease severity, functional status, and prognosis in HCM in cats, it seems reasonable to hope that pimobendan might positively affect outcomes. 

Presumed pro-arrhythmic effect is the reason why pimobendan is not licensed for human use, it would be nice to have a Holter-based study looking at this possibility in cats.  Albeit that dogs don’t seem to suffer the same problem.

Many of the cats in Ward et al. were still alive at the conclusion and there was no control group: precluding meaningful assessment of any survival effect.  There are complicating factors in interpreting response when treating congestive failure in cats generally: 4% of cats in the present study were eventually able to stop medication altogether and may have had ‘transient myocardial thickening’ (which may be thought likely myocarditis). That’s one reason why the dramatic apparent benefit of the small 2014 study have to be treated with caution.

Pimobendan can be sourced in liquid form from Bova.

Feb 21 update… OK, no sooner do you write a pimobendan in cats review when we get a big piece of additional info:

J Vet Intern Med 2021 Feb 5
Effects of pimobendan in cats with hypertrophic cardiomyopathy and recent congestive heart failure: Results of a prospective, double-blind, randomized, nonpivotal, exploratory field study
Karsten E Schober , John E Rush, Virginia Luis Fuentes 3, Tony Glaus 4, Nuala J Summerfield, Kathy Wright, Linda Lehmkuhl, Gerhard Wess, Margaret P Sayer, Joao Loureiro, John MacGregor, Nicole Mohren

https://onlinelibrary.wiley.com/doi/10.1111/jvim.16054

Being prospective and randomized, this has to be viewed as the best-credentialled study to date: although the number of cats enrolled is still not large (eighty‐three cats with HCM and recently controlled CHF: 30 with and 53 without left ventricular outflow tract obstruction).  The main findings:

-The proportion of cats in the full analysis set population with a successful outcome (survival to 180 days after presentation without increased dose of frusemide) was not different between treatment groups (P = .75)

-For cats without LV outflow tract obstruction, the success rate was 32% in pimobendan‐treated cats versus 18.2% in the placebo group.

-For obstructive cats, the success rate was 28.6% and 60% in the pimobendan and placebo groups, respectively.

-No difference was found between treatments for the secondary endpoints of time to furosemide dose escalation or death (P = .89).

-Adverse events in both treatment groups were similar. in cats with HCM that reached the primary 6‐month study endpoint, severity of dynamic LVOTO consistently decreased over time under the influence of pimobendan or placebo in individual cats, lessening concerns regarding long‐term detrimental effects of pimobendan related to dynamic LVOTO

Effectively there is a noticeable division of outcomes between cats with obstruction and those without.  In grouped data these effects tend to balance each other out.  Although the effects in each group were not statistically significant, the authors were prepared to conclude that ‘cats with nonobstructive HCM and recent CHF might benefit from pimobendan whereas cats with LVOTO might not‘.

This becomes the default current position I think. Given occasional cases of hypotension and the fact that pimobendan remains unlicensed in cat (the Vetmedin data sheet bears a contraindication for use in the face of LVOTO) we should be vigilant when treating cats -in particular hypotension would be a concern.