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Clinical Trial
. 2018 Jan;32(1):72-85.
doi: 10.1111/jvim.14885. Epub 2017 Dec 6.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

A Boswood  1 , S G Gordon  2 , J Häggström  3 , G Wess  4 , R L Stepien  5 , M A Oyama  6 , B W Keene  7 , J Bonagura  8 , K A MacDonald  9 , M Patteson  10 , S Smith  11 , P R Fox  12 , K Sanderson  13 , R Woolley  14 , V Szatmári  15 , P Menaut  16 , W M Church  17 , M L O'Sullivan  18 , J-P Jaudon  19 , J-G Kresken  20 , J Rush  21 , K A Barrett  22 , S L Rosenthal  23 , A B Saunders  2 , I Ljungvall  3 , M Deinert  24 , E Bomassi  25 , A H Estrada  26 , M J Fernandez Del Palacio  27 , N S Moise  28 , J A Abbott  29 , Y Fujii  30 , A Spier  31 , M W Luethy  32 , R A Santilli  33 , M Uechi  34 , A Tidholm  35 , C Schummer  36 , P Watson  36
Affiliations
Clinical Trial

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

A Boswood et al. J Vet Intern Med. 2018 Jan.

Abstract

Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described.

Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF.

Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly.

Materials and methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored.

Results: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar.

Conclusions and clinical importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Keywords: Cardiology; Cardiovascular; Echocardiography; Endocardiosis; Heart Failure; Mitral regurgitation.

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Conflict of interest statement

This project was funded by Boehringer Ingelheim Animal Health GmbH. A representative of Boehringer Ingelheim Animal Health GmbH read the final draft before submission. Christoph Schummer and Philip Watson are employees of Boehringer Ingelheim Animal Health GmbH. All other authors have received funding from Boehringer Ingelheim Animal Health GmbH within the last 5 years for some or all of the following activities: research, travel, speaking fees, consultancy fees, and preparation of educational materials.

Figures

Figure 1
Figure 1
A flowchart illustrating the randomization of the 360 dogs in the study, the numbers of dogs reaching the different components of the primary endpoint in each treatment group, and the number of dogs in each treatment group remaining in the per‐protocol population at different scheduled visits. PP, per protocol; CHF, congestive heart failure.
Figure 2
Figure 2
Four box and whiskers plots illustrating absolute values of the change in 4 different echocardiographic variables between baseline and day 35 in the 2 different treatment groups for (A) fractional shortening, (B) normalized left ventricular internal diameter in diastole, (C) left atrial‐to‐aortic ratio and (D) normalized left ventricular internal diameter in systole. The bold horizontal line indicates the median change, the boxes extend from the 25th to the 75th percentile. The whiskers extend from the 2.5th to the 97.5th percentile. P‐values are for between‐group comparisons by a Mann‐Whitney test. Δ, change in; FS%, fractional shortening; LA/Ao, left atrial‐to‐aortic root ratio; LVIDDN, normalized left ventricular internal diameter in diastole; LVIDSN, normalized left ventricular internal diameter in systole.
See this image and copyright information in PMC

References

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