To date, no medication has been proven to prolong the disease-free interval in canine degenerative mitral valve disease (DMVD). Investigators of the Evaluating Pimobendan in Cardiomegaly (EPIC) trial designed a
double-blind, randomized, placebo-controlled multi-center clinical study
to evaluate the effect of pimobendan in dogs with preclinical DMVD and cardiomegaly (Stage B2 ACVIM Heart Failure scale).
The results of the EPIC trial were unveiled the first week of June at the ACVIM Forum in Denver, Colorado.
EPIC began enrolling participants in 2010. Thirty-six veterinary cardiology centers worldwide participated in the study. Asymptomatic, unmedicated dogs greater or equal to 6 years of age between 4.1 and 15kg diagnosed with DMVD and cardiomegaly were enrolled.
In addition to the diagnosis of DMVD via echocardiogram, the dogs had to meet ALL THREE criteria of cardiomegaly to be included in the study:
- Echocardiographic documentation of left atrial enlargement
- Echocardiographic documentation of left ventricular volume load
- Documentation of increased vertebral heart score on right lateral thoracic radiograph.
Patients could have no other heart disease, significant pulmonary hypertension, or any known disease process that could lead to a life expectancy of less than one year. No cardiac medications were allowed in the study. Cough suppressants and bronchodilators were allowed. Dogs received a mean of 0.49mg/kg/day of pimobendan or placebo divided into two doses per day.
In total, 360 dogs were enrolled, and 354 completed the study (which is amazing!). Of those that completed the study, 178 were in the pimobendan group, and 176 were in the placebo group.
The study was planned to run for at least 5 years. The primary endpoint of the study was congestive heart failure diagnosed by clinical signs plus characteristic findings on thoracic radiographs or death presumed to be related to cardiac disease. Blinded investigators reviewed thoracic radiographs, and two-thirds agreed that pulmonary infiltrates consistent with cardiogenic edema were present.
The secondary endpoints included time to first event (CHF, syncope, cough-basically any need to institute precluded cardiac medication) and all-cause mortality.
The study was unblinded after 3½ years, and an interim analysis was performed. The mean time to primary endpoint in the placebo group was 766 days. The mean time to primary endpoint in the pimobendan group was 1228 days-that is a difference of 462 days, or about 15 months! The mean time to death was also significantly longer in the pimobendan group, and 75% of the placebo group had expired by the time of unblinding.
The benefit pimobendan provided to the primary endpoint was so significant that the study was ended immediately in order to allow all patients to receive pimobendan therapy.