CARDIOLOGY
groups. Pimobendan maintained QOL of life for a
longer duration of time, compared to benazepril. The
overall conclusion from the two QUEST studies is that
treatment with pimobendan maintained a good QOL
for longer and increased the survival time by 127 days
compared to benazepril.
The reality of treating patients with heart disease is
that combination therapy is often required. In clinical
practice, pimobendan and benazepril are often used
together with other medications such as furosemide, beta blockers, spironolactone, calcium channel
blockers, etc. These medications are often adjusted
according to the clinical condition of the patient and
require frequent follow up visits.
One the dilemmas in the medical management of
cardiac disease has been when to start treating:
• when patient has evidence of a heart disease such
as a murmur (Stage B)?
• when patient is showing adaptive changes due to
the heart disease (Stage B2)?
• or only when the patient is showing clinical signs
due to heart disease (Stage C)?
Evaluation of the preclinical use of pimobendan started with dilated cardiomyopathy (DCM) in Doberman
Pinschers. This study was known as the PROTECT (Pimobendan Randomized Occult DCM Trial to Evaluate Clinical signs and Time to heart failure) study. The
PROTECT study enrolled Doberman Pinschers between the ages of 4 and 9 years of age that had preclinical echocardiographic evidence of DCM but no
clinical signs related to DCM. The primary end point
of the study was established as the onset of CHF or
sudden death from heart disease. Dogs receiving pimobendan took 718 days to achieve the primary end
point while dogs in the placebo group which took 441
days.
A secondary end point of time from onset of clinical
signs to death from cardiac disease was also evaluated as part of an unblinded study. Dogs receiving
pimobendan survived for a median of 623 days compared to placebo group at 466 days. Similar results
have been shown in Irish wolfhounds where median
time to primary endpoint, onset of CHF or sudden
death, was significantly longer for pimobendan (1,991
days) compared to methyldigoxin (1,263 days) or benazepril HCl (997 days) treated dogs.
The PROTECT study showed that pimobendan treatment of Doberman Pinschers with preclinical disease
(Stage B2) DCM was beneficial due to the delay in the
onset of the clinical signs of CHF. Thus pimobendan
became the first recognised treatment in pre-clinical
DCM in 2012
Research into the use of pimobendan in the preclinical
phase of mitral valve disease started in October 2010
and is known as the EPIC (Evaluation of Pimobendan
in Cardiomegaly) study. The EPIC study was conduct-
vet360
Issue 06 | DECEMBER 2016 | 20
For dogs to be included in the EPIC study
they had to be in Stage B2 heart disease
and also fulfil the following specific criteria:
•
•
•
•
Be 6 years or older,
Weigh between 4.1 and 15 kg,
Have a systolic heart murmur of Gr 3/6 or louder
Have echocardiographic evidence of mitral valve
disease,
• left atrial-to-aortic ratio ≥1.6,
• normalised left ventricular internal diameter
in diastole ≥1.7,
• vertebral heart score (VHS) >10.
ed across 4 continents, 11 countries and 36 trial centres. The EPIC study included 360 dogs and took 5
years to complete.
For dogs to be included in the EPIC study they had to
be in Stage B2 Heart disease and also fulfil the following specific criteria:
a. Be 6 years or older,
b. Weigh between 4.1 and 15 kg,
c. Have a systolic heart murmur of Gr 3/6 or louder
d. Have echocardiographic evidence of mitral valve
disease: left atrial-to-aortic ratio ≥1.6, normalized
left ventricular internal diameter in diastole ≥1.7
and vertebral heart sum (VHS)>10.
Dogs were treated with either pimobendan or a placebo. The primary end-point was the development
of left sided congestive heart failure, euthanasia due
to heart disease or death due to cardiac disease. Left
sided heart failure was considered present when radiographic evidence of cardiogenic pulmonary oedema
(interstitial or alveolar lung pattern) and clinical signs
of heart failure (increased respiratory effort, increase
respiratory rate) were present.
The median time taken for dogs to reach the primary
end point in the pimobendan group was 1228 days
(3.4 years) compared to 766 days (2.1 years) in the placebo group. The difference between the two groups
is 462 days or 15 months. The administration of pimobendan to dogs that met the clinical, radiographic
and echocardiographic inclusion criteria, resulted in a
significant prolongation of the preclinical period.
In summary using pimobendan in MVD in dogs that
meet the inclusion criteria described above, will delay
the onset of clinical disease by a median 462 days.
With good clinical management, the QUEST study
showed us that the use of pimobendan with clinical
heart failure can increase survival time with good quality of life by 127 days compared to benazepril therapy.
Pimobendan may add more quality days to the lives
of canine patients with mitral valve disease if started
in Stage B2 heart failure and continued through into
Stage C heart failure.
REFERENCES available on www.vet360.vetlink.co.za.