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Pimobendan in Asymptomatic Mitral Valve Disease

Clinical Scenario

Bertie is a 6 year old Cavalier King Charles Spaniel  cross who you have just seen for his annual vaccianations. Mrs Malone, his owner has no concerns about this health. You can hear a 3/6 murmur and are concerned about mitral valve disease, though Mrs Malone says Bertie has no cough or exercise intolerance and there are no other cardiovascualr abnormalities on clinical examination. A radiograph of his chest is unremarkable and on a very basic echo you can possibly see a thickened mitral valve and the left atria maybe bigger than it should be. Mrs Malone is very worried about Bertie and wants to do whatever it takes for him and whilst you dont think he is in heart failure you do think he has mitral valve disease. You are aware of some evidence about the use of pimobendan in asymptomatic mitral valve diseas and you wonder what benefit Bertie would have if you started him on pimobendan.....

3-Part Question (PICO)

In [dogs with asymptomatic mitral valve disease] does [pimobendan compared to no treatment] [improve the survival time of affected dogs]?

Search Strategy and Summary of Evidence

Search Strategy

MEDLINE(R) In-Process & Other Non-Indexed Citations and MEDLINE(R) 1946 to Present using the OVID interface

(canine.mp. OR canines.mp. OR canid.mp. OR canids.mp. OR canis.mp. OR canidae.mp. OR dog.mp. OR dogs.mp. OR exp Dogs/ OR exp Canidae/)

AND

(mitral valve disease.mp. OR mitral valve insufficiency.mp. OR mitral valve regurgitation.mp. OR mitral valve incompetence.mp. OR mitral disease.mp. OR mitral insufficiency.mp. OR mitral regurgitation.mp. OR mitral incompetence.mp OR heart failure.mp. OR heart insufficiency.mp. OR heart disease.mp. OR cardiac failure.mp. OR cardiac insufficiency.mp. OR cardiac disease.mp. OR exp Mitral Valve Insufficiency/ OR exp Heart Failure/)

AND

(pimobendan.mp. OR vetmedin.mp. OR inodilator.mp.)

CAB Abstracts 1910 to Present using the OVID interface

(canine.mp. OR canines.mp. OR canid.mp. OR canids.mp. OR canis.mp. OR canidae.mp. OR dog.mp. OR dogs.mp. OR exp dogs/ OR exp Canis/ OR exp Canidae/)

AND

(mitral valve disease.mp. OR mitral valve insufficiency.mp. OR mitral valve regurgitation.mp. OR mitral valve incompetence.mp. OR mitral disease.mp. OR mitral insufficiency.mp. OR mitral regurgitation.mp. OR mitral incompetence.mp OR heart failure.mp. OR heart insufficiency.mp. OR heart disease.mp. OR cardiac failure.mp. OR cardiac insufficiency.mp. OR cardiac disease.mp. OR exp cardiac insufficiency/ OR exp heart diseases/)

AND

(pimobendan.mp. OR vetmedin.mp. OR inodilator.mp.)

Search Outcome

MEDLINE

  • 77 papers found in MEDLINE search
  • 76 papers excluded as they don't meet the PICO question
  • 0 papers excluded as they are in a foreign language
  • 0 papers excluded as they are review articles/in vitro research/conference proceedings
  • 1 total relevant papers from MEDLINE

CAB Abstracts

  • 177 papers found in CAB search
  • 176 papers excluded as they don't meet the PICO question
  • papers excluded as they are in a foreign language
  • 0 papers excluded as they are review articles/in vitro research/conference proceedings
  • 1 total relevant papers from CAB

Total relevant papers

1 relevant papers from both MEDLINE and CAB Abstracts

Summary of Evidence

Boswood et al, 2016, USA, UK, Germany, France, Japan, Sweden, Italy, Spain, Netherlands, Canada, Australia

Title:

Effect of Pimobendan in Dogs with Pre-Clinical Myxomatous Mitral Valve Disease and Cardiomegaly: the EPIC study - a Randomised Clinical Trial

Patient group:


360  enrolled client owned dogs between 4.1 and 15kg over  6 years of age with MMVD (heart murmur at least 3/6 and on echo evideece of valvular lesion, left atrial to aortic ratio > 1.6, normalised left ventricular internal diameter and diastole > 1.7, and vertebral heart score > 10.5)

179 dogs given Pimobendan and 180 given placebo (ITT)

 

Study Type:

Randmoised controlled trial

Outcomes:
  • Time to the composite primary end point: Primary end point was the development of left sided congestive heart failure (CHF) or euthanasia for a cardiac reason or death presumed to be cardiac in originc

Secondary endpoints:

  • Time to the first of one of the events above
  • Time to death of any cause
Key Results:
  • 162/354 dogs reached the primary end point and the median time for all dogs was 433.5 days (IQR 242-718)
  • The proportion of dogs in each group reaching the primary endpoint was not significant (pimobendan 41.6%, placebo 50%)
  • The estimated median time to primary endpoint was 1228 (95% CI 856-NA) days in the placebo group and 766  (95% CI: 667-875) days in the placebo group.
  • The risk of a dog in the pimobendan group reaching the primary end point was lower than the risk in the placebo group, the hazard ratio was 0.64.
  • Median time to first event in pimobendan group (n=130) was 640 days (95% CI: 555-753) and 406 days (95%, CI:316-527) in the placebo group (n=158) (p< 0.0001)
  • No signififcant difference in adverse events
Study Weaknesses:
  • The definition of MVD may not be repeatable in practice as not all measurements can be/are made
  • Part of the primary end point is presumed death due to cardiac diseases - this was not confirmed on post mortem
  • The reasons for euthanasia are complex and numerouswhich may lead to variability in the time to the primary end point.
  • The study was sponsored by a manufacturer of pimobendan
Attachment:
Evidence appraisalEvidence appraisal

Comments

In the study found, mitral valve disease was defined very specifically and the study showed that dogs affected in this way had a survival advantage over the dogs who received placebo. This doesnt mean all dogs with MVD will have this advantage and many dogs will not have the disease diagnosed in such a precise manner.

Dogs witth some concurrent diseases were excluded from entering the trial.

It is unknown how long the survival advantage of being on pimobendan, versus no treatment, will last for in dogs with asymptomatic MVD.

Bottom line

Yes, in the one study found the dogs with MVD (defined on echocardiographic, radiographic apprearances and the presence of a murmur) that were given pimobendan lived (on average) 15 months longer than those who received no treatment.  

Disclaimer

The BETs on this website are a summary of the evidence found on a topic and are not clinical guidelines. It is the responsibility of the individual veterinary surgeon to ensure appropriate decisions are made based on the specific circumstances of patients under their care, taking into account other factors such as local licensing regulations. Read small print

References

Boswood A, Häggström J, Gordon SG, et al. 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. 2016;30(6):1765-1779. doi:10.1111/jvim.14586 

This paper is open access: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.14586 

About this BET

First author:
Second author:
Institution:

This BET was authored by Tim Shearman and Rachel Dean

VetPartners, York 

Search last performed:
2019-02-28 17:07:16
Original publication date:
2019-02-28 17:07:16
Last updated:
2019-02-28 17:07:16
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