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 - Tập 30 Số 6 - Trang 1765-1779 - 2016
Adrian Boswood1, Jens Häggström2, Sonya G. Gordon3, Gerhard Wess4, Rebecca L. Stepien5, Mark A. Oyama6, Bruce W. Keene7, John D. Bonagura8, Kristin A. MacDonald9, Mark Patteson10, Sarah Smith11, Philip R. Fox12, Karen Sanderson13, Richard Woolley14, Viktor Szatmári15, Pierre Menaut16, Whitney M. Church17, M. Lynne O’Sullivan18, J.‐P. Jaudon19, Jan‐Gerd Kresken20, John E. Rush21, Kirstie A. Barrett22, Steven L. Rosenthal23, Ashley B. Saunders3, Ingrid Ljungvall2, Michael Deinert24, Eric Bomassi25, Amara H. Estrada26, María Josefa Fernández del Palacio27, N. Sydney Moïse28, Jonathan A. Abbott29, Yoko Fujii30, Alan W. Spier31, Michael W. Luethy32, Roberto A. Santilli33, Masami Uechi34, Anna Tidholm35, Philip Watson36
1Department of Veterinary Clinical Sciences The Royal Veterinary College Hatfield Hertfordshire UK
2Department of Clinical Sciences Swedish University of Agricultural Sciences Uppsala SE
3Small Animal Clinical Science Texas A&M University College Station TX
4Clinic of Small Animal Medicine University of Munich Munich Germany
5Medical Sciences University of Wisconsin Madison School of Veterinary Medicine Madison WI
6Clinical Studies-Philadelphia MJR-VHUP-Cardiology University of Pennsylvania Philadelphia PA
7Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC
8Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH
9Animal Care Center Rohnert Park CA
10HeartVets @ Vale Referrals The Animal Hospital Dursley Gloucestershire UK
11Sarah Smith Cardiology Derby UK
12Animal Medical Center, New York, NY
13Rocky Mountain Veterinary Cardiology Boulder CO
14Cardio Respiratory Pet Referrals Victoria Mordialloc Vic Australia
15Faculty of Veterinary Medicine Clinical Sciences of Companion Animals Utrecht University Utrecht Utrecht Netherlands
16Internal Medicine and Cardiology Clinique Vétérinaire Aquivet Eysines France
17Desert Veterinary Medical Specialists Phoenix AZ
18Deptartment of Clinical Studies University of Guelph Ontario Veterinary College Guelph ON Canada
19Clinique Veterinaire Des Etangs Villars Les Dombes France
20Clinic for Small Animals Kaiserberg Duisburg Germany
21Clinical Sciences Tufts University Cummings School of Veterinary Medicine North Grafton MA
22Cardiology VCA West Los Angeles Los Angeles CA
23Cardiac Care for Pets Towson MD
24Tierklinik am Sandpfad Wiesloch Germany
25Cardiology Centre Hospitalier Vétérinaire des Cordeliers Meaux France
26Small Animal Clinical Sciences University of Florida College of Veterinary Medicine Gainesville FL
27Medicina y Cirugía Animal Universidad de Murcia Murcia Murcia Spain
28Clinical Sciences College of Veterinary Medicine Cornell University Ithaca NY
29Department of Small Animal Clinical Sciences Virginia Tech Virginia-Maryland College of Veterinary Medicine Blacksburg VA
30Azabu University Chuo-ku Sagamihara Kanagawa Japan
31Blue Pearl Veterinary Partners Tampa FL
32Chicago Veterinary Emergency and Specialty Center Chicago IL
33Cardiology Clinica Veterinaria Malpensa Viale Marconi Varese Italy
34JASMINE Veterinary Cardiovascular Medical Center Japan Animal Specialty Medical Institute Inc. Yokohama Japan
35Djursjukhuset Albano Danderyd Sweden
36Boehringer Ingelheim Animal Health, Ingelheim am Rhein, Germany

Tóm tắt

BackgroundPimobendan 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/ObjectivesAdministration 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.Animals360 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.MethodsProspective, 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.ResultsMedian 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 ImportanceAdministration 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.

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Journal of Veterinary Internal Medicine

Tập 30 Số 6

1765-1779

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