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Canine heart medications: where are we in 2017?

A couple of years ago it seemed we were all more or less clear on this but, somehow, the more studies we have the muddier the waters are getting (sigh).

If you want the concise version of where we are now, in my interpretation, then this is it:

It’s worth noting that cardiology diplomates are less than unanimous on some of these issues.  And my observation would be that, as a group, the stated opinions of diplomates haven’t always reflected the published evidence base.

The situation is inevitably clouded by potential conflicts of interests.  If you want the ‘Devil’s advocate’ case you can read it here:

http://www.cavalierhealth.org/blog.htm

It’s one perspective: probably a bit unkind about the motives of a lot of veterinary cardiologists and a selective interpretation of ‘statistically significant’.  Certainly some some important issues raised

To look at the data for drugs group by group.

1: Everybody agrees we should use loop diuretics in dogs with CHF.  Hurrah, so far so good.

2: ACE inhibitors:  all of these studies involve relatively small numbers of individuals -especially when one looks at the numbers reaching relevant endpoints

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.  Not especially convincing.

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.

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 for both DCM and MMVD dogs.

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.

VALVE (2017 only preliminary results available) Long term survival benefit of ramipril + pimobendan + frusemide (triple therapy) c0mpared to pimobendan + frusemide (double therapy) in 158 MMVD-affected dogs with CHF.  No benefit or detriment with addition of ACEi.

3: Pimobendan

QUEST (2008) Long term survival benefit of benazepril + frusemide compared to pimobendan + frusemide in 260 MMVD-affected dogs with CHF.  Median survival 267 days in pimobendan group, 140 days  in benazepril group.

EPIC (2016) Long term effect of pimobendan in delaying onset of CHF in 360 asymptomatic MMVD-affected dogs with a specific subset of class B heart disease (mostly B2; arguably some of them B1 since inclusion criteria would encompass normal heart dimensions in some breeds). Much debated results demonstrate prolongation of CHF-free period by a median of 15 months and survival by 5 months.  However, within this population of dogs are many with mild remodelling which may never reach CHF at all (and thus receive no benefit).  The inclusion criteria are so broad as to leave room for much debate as to whether pimobendan should routinely be prescribed to all dogs in B2.

4: Spironolactone

Bernay et al (2010) study of 221 MMVD-affected dogs

http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2009.0467.x/abstract

Potential limitations eloquently described here:

http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2010.0622.x/full

…these cast significant doubt on stated findings