Dataset Information

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

ABSTRACT:

Background

Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown.

Hypothesis/objectives

Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia.

Animals

360 client-owned dogs with MMVD with left atrial-to-aortic ratio ?1.6, normalized left ventricular internal diameter in diastole ?1.7, and vertebral heart sum >10.5.

Methods

Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia.

Results

Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012).

Conclusions and clinical importance

Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

SUBMITTER: Boswood A

PROVIDER: S-EPMC5115200 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

Boswood A A Häggström J J Gordon S G SG Wess G G Stepien R L RL Oyama M A MA Keene B W BW Bonagura J J MacDonald K A KA Patteson M M Smith S S Fox P R PR Sanderson K K Woolley R R Szatmári V V Menaut P P Church W M WM O'Sullivan M L ML Jaudon J-P JP Kresken J-G JG Rush J J Barrett K A KA Rosenthal S L SL Saunders A B AB Ljungvall I I Deinert M M Bomassi E E Estrada A H AH Fernandez Del Palacio M J MJ Moise N S NS Abbott J A JA Fujii Y Y Spier A A Luethy M W MW Santilli R A RA Uechi M M Tidholm A A Watson P P

Journal of veterinary internal medicine 20160928 6

<h4>Background</h4>Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown.<h4>Hypothesis/objectives</h4>Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia.<h4>Animals ...[more]

PMID: 27678080

Similar Datasets

Project description:BackgroundPimobendan is a widely used medication for the treatment of dogs with congestive heart failure (CHF) and preclinical degenerative mitral valve disease (DMVD) with cardiomegaly. The benefit of a treatment in dogs with preclinical DMVD but without cardiomegaly has not yet been elucidated. Some positive effects concerning life quality and a decrease in cardiac biomarkers could be verified. This study aimed to further investigate these results using a placebo-controlled double-blinded crossover design. Out of a total of 15 dogs, eight were allocated to sequence-group AB, in which dogs received pimobendan (A) during the first treatment period and placebo (B) during the second period. Accordingly, sequence-group BA was treated first with placebo followed by pimobendan. Each treatment period lasted six months and included a baseline investigation and follow-ups after 90 and 180 days. The investigations included a questionnaire completed by the owners, echocardiographic examination, and measurements of NT-proBNP, cTnI and lactate before and after a standardised submaximal exercise test.ResultsNT-proBNP values decreased significantly during the treatment period with pimobendan, and the post-exercise increase was attenuated at day 180. No significant treatment effects could be verified for cTnI and lactate, neither pre- nor post-exercise. Left ventricular size decreased under treatment, whereas no significant changes in left atrial size were detected. The owners described their dogs under treatment with pimobendan as being more active at day 90 (11/15) and day 180 (12/15). Those animals treated with placebo were described as being more active at day 90 (2/15) and day 180 (5/15).ConclusionsPimobendan had reducing effects on the concentrations of pre- and post-exercise cardiac biomarkers and the size of the left ventricle in dogs with DMVD ACVIM B1. Exercise testing in addition to an assessment of cardiac biomarkers might improve the decision when to initiate pimobendan treatment in dogs with DMVD.

Project description:Canine myxomatous mitral valve disease (MMVD) is similar to Barlow's form of MMVD in humans. These valvulopathies are complex, with varying speeds of progression. We hypothesized that the relative abundances of serum proteins would help identify the consecutive MMVD stages and discover new disease pathways on a systemic level. To identify distinction-contributing protein panels for disease onset and progression, we compared the proteomic profiles of serum from healthy dogs and dogs with different stages of naturally occurring MMVD. Dogs were divided into experimental groups on the basis of the left-atrium-to-aorta ratio and normalized left ventricular internal dimension in diastole values. Serum was collected from healthy (N = 12) dogs, dogs diagnosed with MMVD in stages B1 (N = 13) and B2 (N = 12) (asymptomatic), and dogs diagnosed with MMVD in chronic stage C (N = 13) (symptomatic). Serum biochemistry and selected ELISAs (galectin-3, suppression of tumorigenicity, and asymmetric dimethylarginine) were performed. Liquid chromatography-mass spectrometry (LC-MS), tandem mass tag (TMT) quantitative proteomics, and statistical and bioinformatics analysis were employed. Most of the 21 serum proteins with significantly different abundances between experimental groups (p < 0.05, FDR ˂ 0.05) were classified as matrix metalloproteinases, protease inhibitors, scaffold/adaptor proteins, complement components, anticoagulants, cytokine, and chaperone. LC-MS TMT proteomics results obtained for haptoglobin, clusterin, and peptidase D were further validated analytically. Canine MMVD stages, including, for the first time, asymptomatic B1 and B2 stages, were successfully distinguished in dogs with the disease and healthy dogs on the basis of the relative abundances of a panel of specific serum proteins. Most proteins with significantly different abundances were involved in immune and inflammatory pathways. Their role in structural remodeling and progression of canine MMVD must be further investigated. Further research is needed to confirm the resemblance/difference with human MMVD. Proteomics data are available via ProteomeXchange with the unique dataset identifier PXD038475.

Dataset Information

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

Background

Hypothesis/objectives

Animals

Methods

Results

Conclusions and clinical importance

Publications

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

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