Page 281 - Clinical Small Animal Internal Medicine

25 Valvular Heart Disease 249

significant effect of angiotensin converting enzyme together with furosemide in stage C dogs is based on evi-
VetBooks.ir inhibitor (ACEI) therapy on the primary outcome varia- dence provided by several multicenter double‐blind
studies which provide evidence that an ACEI added to
ble, which was time from inclusion in the study to the
onset of signs of CHF. Based on these results and the
life and survival time.
observation that only a relatively small percentage of therapy including furosemide improved the quality of
dogs with asymptomatic disease progress to CHF or die Two recent studies have shown that pimobendan
as a consequence of the disease, the author does not improved survival and quality of life in stage C dogs
support treatment with an ACEI. compared to standard treatment with an ACEI and
A recent multicenter clinical trial reported that furosemide. The first study was conducted as a blinded,
pimobendan delays onset of congestive heart failure in a randomized, positive‐controlled, multicenter study and
subpopulation of dogs with stage B2. It should be high- included 76 dogs. The study had a mandatory 56‐day
lighted that enrolled dogs had significant cardiomegaly treatment period that was followed by an optional long‐
identified by specific echocardiographic criteria. It is term treatment phase. In this study, pimobendan sig-
possible, although not proven, that dogs in advanced nificantly improved a clinical measure of disease severity
stage B2 may benefit from other medical treatments and survival. The results of this study led to a larger
such as spironolactone. This emphasizes the importance study in 260 dogs with stage C MMVD. This was a pro-
of developing biomarkers able to identify patients at spective multicenter randomized single‐blinded study
higher risk for developing CHF. A study conducted on and the primary endpoint was a composite of cardiac
72 asymptomatic dogs with MMVD showed that NT‐ death, euthanasia for heart failure, or treatment failure.
proBNP at a cut‐off of 466 pmol/L had 80% sensitivity Dogs were randomized to therapy with either ACEI or
and 76% specificity in predicting 12‐month progression pimobendan. Pimobendan was associated with signifi-
to cardiac death or CHF. Although these data appear cant improvement in the endpoint variables and this
very promising, further studies are needed to confirm benefit persisted after adjusting for all baseline varia-
the value of NT‐proBNP in distinguishing those patients bles. All dogs enrolled in this study were on concomi-
that will progress to CHF. Accordingly, assessment of tant furosemide treatment. It should be stressed that
stage B dogs should include evaluation of multiple none of these studies answer the question of whether
parameters including clinical, radiographic, and echo- triple therapy involving furosemide, ACEI, and
cardiographic findings. pimobendan would be superior to double therapy with
pimobendan plus furosemide. The ACVIM consensus
The Symptomatic Dog (Stage C: ACVIM Consensus) recommended that chronic management of stage C
According to the ACVIM consensus, stage C includes dogs includes a combination of ACEI, pimobendan, and
animals with MMVD and current or previous clinical furosemide.
signs of CHF. Management of these patients is based on Spironolactone has been recently approved in Europe
administration of a combination of several medications, for treatment of dogs with MMVD. In one study, spirono-
including diuretics, ACEIs, and pimobendan. Although lactone when added to furosemide and ACEI +/− digoxin
no study has proven the efficacy of furosemide in dogs decreased risk of cardiac‐related death or euthanasia for
with MMVD, there is a general consensus that diuretics cardiac reasons by 69% in dogs with moderate to severe
are essential for patients with CHF. The majority of dogs MMVD. The dosage of spironolactone used in the clini-
enrolled in the multicenter studies evaluating the efficacy cal trial was 2 mg/kg q24h. One criticism of this study is
of the ACEI and pimobendan in symptomatic dogs with that a relatively low number of cases reached the end-
MMVD were on concomitant treatment with furosem- point compared to other studies evaluating stage C dogs.
ide. The diagnosis of CHF should be reevaluated if One possible mechanism of action for spironolactone
diuretics do not improve clinical signs in dogs with sus- would be related to its antifibrotic effects. Geriatric dogs
pected CHF. The dosage of furosemide should be affected by MMVD have intramyocardial arterial
adjusted in order to keep the patients free from clinical changes associated with areas of replacement fibrosis.
signs. Although the suggested mean dosage for these The exact role of vascular or myocardial fibrosis in the
patients is 2 mg/kg PO q12h, it could range from 0.5 mg/ pathogenesis of MMVD is still to be clarified. Positive
kg PO q12h to 4–6 mg/kg PO q8h. effects of aldosterone blockers such as spironolactone
In human patients with CHF, teaching patients to could also be related to the mechanism of aldosterone
adjust their furosemide dosage on the basis of monitor- escape. Aldosterone concentrations can be elevated in
ing their weight and their clinical signs significantly dogs with MMVD despite receiving an ACEI. This phe-
reduces the number of hospitalizations and may be asso- nomenon is dependent on the dose of concomitant furo-
ciated with prolonged survival. A similar approach with semide and has been attributed to incomplete inhibition
dogs in CHF is desirable but difficult. The use of an ACEI of ACE activity.