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


OBJECTIVE
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.


METHODS
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
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.
Department of Veterinary Clinical Sciences, The Royal Veterinary College, Hatfield, Hertfordshire, UK.
A
A
Boswood
Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, SE.
J
J
Häggström
Small Animal Clinical Science, Texas A&M University, College Station, TX.
S G
SG
Gordon
Clinic of Small Animal Medicine, University of Munich, Munich, Germany.
G
G
Wess
Medical Sciences, University of Wisconsin Madison School of Veterinary Medicine, Madison, WI.
R L
RL
Stepien
Clinical Studies-Philadelphia, MJR-VHUP-Cardiology, University of Pennsylvania, Philadelphia, PA.
M A
MA
Oyama
Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, NC.
B W
BW
Keene
Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH.
J
J
Bonagura
Animal Care Center, Rohnert Park, CA.
K A
KA
MacDonald
HeartVets @ Vale Referrals, The Animal Hospital, Dursley, Gloucestershire, UK.
M
M
Patteson
Sarah Smith Cardiology, Derby, UK.
S
S
Smith
Animal Medical Center, New York, NY.
P R
PR
Fox
Rocky Mountain Veterinary Cardiology, Boulder, CO.
K
K
Sanderson
Cardio Respiratory Pet Referrals Victoria, Mordialloc, Vic, Australia.
R
R
Woolley
Faculty of Veterinary Medicine, Clinical Sciences of Companion Animals, Utrecht University, Utrecht, Utrecht, Netherlands.
V
V
Szatmári
Internal Medicine and Cardiology, Clinique Vétérinaire Aquivet, Eysines, France.
P
P
Menaut
Desert Veterinary Medical Specialists, Phoenix, AZ.
W M
WM
Church
Deptartment of Clinical Studies, University of Guelph, Ontario Veterinary College, Guelph, ON, Canada.
M L
ML
O'Sullivan
Clinique Veterinaire Des Etangs, Villars Les Dombes, France.
J-P
JP
Jaudon
Clinic for Small Animals Kaiserberg, Duisburg, Germany.
J-G
JG
Kresken
Clinical Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA.
J
J
Rush
Cardiology, VCA West Los Angeles, Los Angeles, CA.
K A
KA
Barrett
Cardiac Care for Pets, Towson, MD.
S L
SL
Rosenthal
Small Animal Clinical Science, Texas A&M University, College Station, TX.
A B
AB
Saunders
Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, SE.
I
I
Ljungvall
Tierklinik am Sandpfad, Wiesloch, Germany.
M
M
Deinert
Cardiology, Centre Hospitalier Vétérinaire des Cordeliers, Meaux, France.
E
E
Bomassi
Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL.
A H
AH
Estrada
Medicina y Cirugía Animal, Universidad de Murcia, Murcia, Murcia, Spain.
M J
MJ
Fernandez Del Palacio
Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.
N S
NS
Moise
Department of Small Animal Clinical Sciences, Virginia Tech, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA.
J A
JA
Abbott
Azabu University, Chuo-ku, Sagamihara, Kanagawa, Japan.
Y
Y
Fujii
Blue Pearl Veterinary Partners, Tampa, FL.
A
A
Spier
Chicago Veterinary Emergency and Specialty Center, Chicago, IL.
M W
MW
Luethy
Cardiology, Clinica Veterinaria Malpensa, Viale Marconi, Varese, Italy.
R A
RA
Santilli
JASMINE Veterinary Cardiovascular Medical Center, Japan Animal Specialty Medical Institute Inc., Yokohama, Japan.
M
M
Uechi
Djursjukhuset Albano, Danderyd, Sweden.
A
A
Tidholm
Boehringer Ingelheim, Animal Health, Ingelheim am Rhein, Germany.
P
P
Watson
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000662:veterinary*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality / Q000662:veterinary; D008297:Male; D008944:Mitral Valve Insufficiency / Q000188:drug therapy / Q000401:mortality / Q000662:veterinary*; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan
Asymptomatic; Echocardiography; Endocardiosis; Heart failure; Mitral regurgitation; Prevention; Treatment; Vertebral heart sum
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