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EPIC CARDIAC DRUG STUDY TERMINATED EARLY 
- TREATED SUBJECTS LIVED LONGER
By Merrilee Small, DVM, DACVIM (Cardiology)
June 2016
Background
Pimobendan

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.

Participants

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:
  1. Echocardiographic documentation of left atrial enlargement
  2. Echocardiographic documentation of left ventricular volume load
  3. 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.
 
Outcome
 
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.

Comments

Dogs were diagnosed with echocardiography AND had to meet certain inclusion criteria. This data cannot be applied to every dog with a murmur or even subjective radiographic cardiomegaly. This study investigated a very specific group of dogs, and global assumptions cannot be made about patients of larger size or with other disease conditions. Fortunately, MVD is the most common disease treated in veterinary medicine.
 
Cost/benefit must be considered since pimobendan is not inexpensive. The longest survivors were on pimobendan for 4 years.

If you have questions regarding the treatment of MVD or other cardiac conditions for your patients, please do not hesitate to contact Merrilee Small, DVM, DACVIM (Cardiology) at 757.935.9111 or info@thecovevets.com .
TECH TIP:  TPRs and Tips for Thoracic Radiographs 
By Andi Davis, LVT and Marie Moore, LVT
DV and right lateral are preferred for cardiac evaluation

T: Technique
  • Measure, use appropriate settings, and record. 
  • A lighter image is always preferred.
*Tech Tip: Document measurements and settings. Refer to these for serial radiographs to ensure comparing apples to apples.
 
P: Positioning
  • DV/VD - Vertebra and sternum should be in alignment. 
  • Forelimbs should not be in chest cavity.
*Tech Tip: Consider using "V trough" to help align patient and keep limbs out of chest. DV view of thorax preferred when evaluating for cardiovascular disease as pulmonary vasculature is more readily evaluated.
  • R. Lat. - Ribs should be superimposed. 
  • Shoulder blades should be aligned and out of the chest cavity. 
Malpositioned
Properly positioned
R: Respiration and Rotation
  • Respiration: Take at peak inspiration. 
  • Avoid panting to prevent motion artifact. 
  • You should be able to see a triangle behind the heart (in lateral view), the larger the more inspiratory the film (see pictures below).
*Tech Tip: For panting animals, occlude nostrils briefly and release to catch peak inspiration. Coughing dogs may require a low dose of Butorphanol to calm down (0.2mg/kg) IM or IV.

Malpositioned
Properly positioned
  • Rotation: DV - Ribs should be superimposed. 
  • A clean cut versus seeing the curve of the ribs.
  • Rotation: R. Lat. - No ribs should be visible over the spine (spinal rotation). 
*Tech Tip: Rotate sternum down for obese dogs and up for thin dogs. A towel can be folded and placed under the shoulder to elevate and align the rib cage if necessary.
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