QUEST - Pimobendan, Benazepril etc...

Re: QUEST - Pimobendan, Benazepril etc...

Brad O'Hagan — Tue, 30 Jun 2009 00:53:10 GMT

This is an interesting thread

[quote user="Mark Frost"]However, without a trial showing evidence of greater success using both pimobendan and benazepril plus frusemide, does that mean its not right to use them both?[/quote]

Abscence of published evidence is not evidence of absence of effect.

An often discussed but never peer-review published study called the PITCH study (Lombard, C (2000). Clinical experience with pimobendan. Proceedings of the Veterinary Cardiovascular Society, Pre-BSAVA Meeting.) actually did look at combining all three medications. There were several study flaws, such as being comlicated by enrolling both DCM and MVD/TVD cases and some poor statistical power in some groups, however reading the results section of the conference paper there are a couple of stand out comments

"There was significance in favour of pimobendan and combination therapy in comparison to benazepril"

"In dogs not reomved from the study due to lack of efficacy or death, the NYHA-classification improved from 3.3 to 2.3 in the pimobendan group, 3.3 to 2.3 in the benazepril group and 3.4 to 2.1 in the combination therapy group."

"Combination (of pimobendan) with benazepril was not associated with additional clinically relevant benefits in comparison to pimobendan monotherapy."

i find this last statement a little curious as this would appear to contradict the previous comment. A lower percentage of patients were also removed from the study due to ineffciacy or death when treated with combination therapy (8%) compared to pimobendan (11%) or benazepril (34%).

I agree that we are not ever likely to see a large scale, properly controlled investigation of combination therapy whilst ever pimobendan is on patent - as patent protection expires it is possible that there will be scientific investigation in to combination formulation and then we may actually see the answers.

Re: QUEST - Pimobendan, Benazepril etc...

Rajat — Fri, 26 Jun 2009 19:08:13 GMT

Hi Alison

Spiro is meant to be quite useful in preventing fibrosis caused Aldosterone, human studies have shown a significant impact on mortality (search for RALES on pubmed) , and the vet study should be coming out soon this summer (if not already).

My approach is like Alex's, although I usually add in spiro( at a lowish dose - the benefits in the human paper were seen at a much lower dose than used for diuresis) where I can - costs/O and dog compliance allow.

As for Pimo doses- depends where you read, but the dose range is .2-.6 mg/kg/day divided into two. So you could have a situation where the patient is on double the dose someone else may prescribe.

Cheers

Raj

Re: QUEST - Pimobendan, Benazepril etc...

sophia guymer — Mon, 15 Jun 2009 20:41:56 GMT

[quote user="alex gough"]

Clear as mud?

[/quote]

Yes, well no, what I mean is, yes it is clear but not as mud .

Thanks for pointing that out.

Sophia

Re: QUEST - Pimobendan, Benazepril etc...

Alex Gough — Fri, 12 Jun 2009 18:25:44 GMT

Sorry, the QUEST trial was on MVD, not DCM. I dont think there are any good studies that show that pimo+frus+ACEi is superior to pimo+frus for mitral valve disease. Nor possibly any studies that show that pimo+frus+ACEi is superior to pimo+frus for DCM, not that immediately spring to mind anyway. The above study shows that pimo+frus+ACEi was better than frus+ACEi for DCM.

Clear as mud?

Alex

Re: QUEST - Pimobendan, Benazepril etc...

sophia guymer — Thu, 11 Jun 2009 21:02:16 GMT

[quote user="alison howell"]

Surely there must be some kind of evidence that the combination works better than one of them given singly?

[/quote]

I think this is? Or am I not reading it properly?

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy.

O'Grady MR, Minors SL, O'Sullivan ML, Horne R.

Department of Clinical Studies, the Ontario Veterinary College, University of Guelph, Guelph, ON, Canada. mogrady@uoguelph.ca

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.

PMID: 18537880 [PubMed - indexed for MEDLINE]

Re: QUEST - Pimobendan, Benazepril etc...

sophia guymer — Thu, 11 Jun 2009 20:50:27 GMT

[quote user="Mark Frost"]

You'll find all the info you want on the above links...

[/quote]

Thank you very much, Mark, that was very helpful!

Re: QUEST - Pimobendan, Benazepril etc...

Mark Frost — Wed, 10 Jun 2009 21:05:52 GMT

[quote user="sophia guymer"]

[quote user="Mark Frost"]The QUEST trial gives us an evidence based way of deciding (in MVD anyway)[/quote]

Ok, I am going to have to admit ignorance now, I have been out for a few years and only work 2 mornings a week now (always with 1 or 2 others present to ask lots of questions if need be). Can someone explain to me what 'the QUEST trial' is? I can sort of understand the rest of the thread but have no idea what is meant by the QUEST trial.

Sophia

[/quote]

Quest Trial Website

Pub Med Abstract of Paper

You'll find all the info you want on the above links...

Re: QUEST - Pimobendan, Benazepril etc...

sophia guymer — Wed, 10 Jun 2009 20:22:59 GMT

[quote user="Mark Frost"]The QUEST trial gives us an evidence based way of deciding (in MVD anyway)[/quote]

Sophia

Re: QUEST - Pimobendan, Benazepril etc...

vs0u — Wed, 10 Jun 2009 09:46:15 GMT

How much use is spironolactone? Cardiologists always seem to use it but does it make much difference?

Also, I recently came across a case of a great dane with DCM which had been put on pimobendan at twice the normal dosage. It had been seen by a cardiologist so may have been intentional (and the dog has done amazingly well). Is this a normal thing to do?

Re: QUEST - Pimobendan, Benazepril etc...

Alex Gough — Tue, 09 Jun 2009 20:39:44 GMT

[quote user="alison howell"]I always thought you were not supposed to use frusemide without an ACE inhibitor as it reduces survival times?[/quote]

Yep. Using frusemide activates the RAA system, which is the opposite of what you want, so frusemide should generally be used with an ACEi if you are treating heart failure.

However, I think pimobendan has an indirect rather than a direct effect on the RAAS, so it is theoretically ok to use frusemide with pimo and not an ACEi, and the QUEST trial showed that if you do that, the survival time is better than ACEI + fruse.

No evidence, as Kieran says, that ACE + pimo + frus is better than pimo + frus, but it probably is. My approach now is to use pimo + ACEi + frus where funds allow, and pimo + frus where funds are tight,

Alex Gough MA VetMB CertSAM CertVC MRCVS

Bath Vet Referrals

Re: QUEST - Pimobendan, Benazepril etc...

Kieran Borgeat — Tue, 09 Jun 2009 17:05:06 GMT

It's certainly not contraindicated to use both, and there are arguements for doing so. Most cardiologists that I have worked with will start dogs with MVD or DCM on furosemide, pimobendan and an ACE inhibitor as initial therapy.

It is unlikely that there will be a good trial done to evaluate the use of both pimo and ACEi drugs vs either/or.

Re: QUEST - Pimobendan, Benazepril etc...

vs0u — Tue, 09 Jun 2009 17:04:25 GMT

I always thought you were not supposed to use frusemide without an ACE inhibitor as it reduces survival times?

So you could start off with just pimobendan but when it got to a point where frusemide is needed you would have to start benazepril at the same time.

Surely there must be some kind of evidence that the combination works better than one of them given singly?