Canine heart medications: the evidence -late 2020 update
It pays to keep this situation under constant review. The more evidence emerges, the more there is to think about.
The ACE inhibitor evidence in summary:
IMPROVE study (1995): short term effects of enalapril over 21 days in heterogeneous group of dogs with CHF; conclusions rely quite heavily on subjective criteria. More benefit in DCM than in MVD. Not especially convincing to my eyes.
COVE (1995): short-term effects of enalapril over 1 month in a heterogeneous group of 211 dogs with CHF ; 20% were Dobermans, 33% DCM, 66% MMVD. Some debatable subjective criteria. Objectively, one death in enalapril group 1 v 9 deaths in placebo group. Again benefit was largely confined to DCM dogs.
VETPROOF (2007) long term survival benefits of enalapril in 124 asymptomatic MMVD dogs. Little or no delay in onset of CHF demonstrated.
SVEP (2002) long term survival benefits of enalapril in 229 asymptomatic MMVD affected CKCS. No benefit in delaying onset of CHF demonstrated.
LIVE (1998) long term survival benefit of enalapril in 110 CHF dogs with DCM or MMVD. Significant benefits reported for both DCM and MMVD dogs. Subsequent analysis of the data (see Rishniw article below) has suggested that the benefit was significant only in DCM.
BENCH (1999) survival benefits in a heterogeneous group of 162 dogs with CHF; difficult to interpret. Various design issues. Unexplained ‘a bit too good to be true’ outcomes with benazepril. To give you an idea: median survival or time to treatment failure for MMVD dogs receiving frusemide + benazepril in BENCH was 436 days where the analogous figure for the same treatment regime in QUEST was 111 days. A majority of dogs in BENCH were included on the basis of ISACHC stage II heart failure. That would include dogs with, for example, cough. Although there was a bland assertion that dogs were included on the basis of a diagnosis of heart failure after thorough work-up, subsequent evolution of our understanding of canine cardiothoracic disease raises a significant question mark over whether these dogs really were all in CHF. Especially since clinical signs are reported by the authors to have been present for up to 72 months before admission to the study (!).
VALVE (2020) Long term survival benefit of ramipril + pimobendan + frusemide (triple therapy) compared to pimobendan + frusemide (double therapy) in 156 MMVD-affected dogs with CHF. No benefit or detriment with addition of ACEi. It’s a slight concern that the ramipril-treated dogs survived 41 days less than the frus + pimo group although this was not statistically significant.
An interesting read is Mark Rishniw’s piece from February this year
Angiotensin-Converting Enzyme Inhibitors and Cardiac Disease: Have They Had Their Day? Mark Rishniw. Advances in Sm. Anim. Med. & Surg. February 2020;33(2):1-3
https://www.sciencedirect.com/science/article/abs/pii/S1041782620300189?via%3Dihub
to quote the Dr…
‘In retrospect, it became clear that the veterinary community was hoodwinked into believing that ACE-I were the medical cure for CHF dogs because of corporate marketing decisions.’
and
‘So, what does all this mean? My interpretation of all this literature suggests that ACE-I have no place in managing mitral valve disease, whether in dogs with CHF or dogs with subclinical disease‘.
Ouch!
Personally, I think one could probably defend the assertion that enalapril is a reasonable option in dogs with CHF due to primary myocardial failure (‘DCM’…..which should really be re-named ‘PMF’ in common parlance).
And spironolactone is no better..
The 2010 paper which represents most of the evidence:
Efficacy of spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve Disease. F. Bernay, J.M. Bland, J. Häggström, L. Baduel, B. Combes, A. Lopez, and V. Kaltsatos. J Vet Intern Med, Mar/Apr 2010;24(2):331-341
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1939-1676.2009.0467.x
..was, I believe, sponsored by the manufacturers and has been the subject of subsequent criticism by some very eminent cardiologists
Efficacy of Spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve Disease. M.D. Kittleson, J.D. Bonagura. J. Vet. Intern. Med. November 2010;24(6):1245-1246
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1939-1676.2010.0622.x
A letter which concludes..
‘Thus, we respectfully dispute that a survival benefit of spironolactone in canine MR is proven‘
So…….in addition to the actual evidence as published, we have to consider the politics of who has funded the studies, whose opinions might have been influenced by ‘political’ considerations and the danger that there may be professional reputations and jealousies at stake in all of this.
In summary the evidence to support the routine use of spironlactone or ACE-inhibitors in canine heart disease is weak. Enalapril in primary myocardial failure is a possible exception to that generalisation.
I don’t quite have the energy to tackle loop diuretics and pimobendan in full right now but I can’t see any reason not to use torsemide/torasemide as first line diuretic in dogs as previously blogged.
