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death (718 days, IQR 441–1152 days versus the placebo group 441 days, IQR 151–641 days, P = 0.0088). and increased survival time (623 days, IQR 491–1531 days versus the placebo group 466 days, IQR 236–710 days, P = .034). Furthermore, pimobendan conferred a reduction cardiac size, a reduction that appeared to be primary effector for the increased preclinical period and survival.
Studies in dogs with clinical heart disease
To study the effect of pimobendan on survival in dogs with CHF secondary to MMVD the QUEST study was undertaken. The aim of the study was to compare
the time taken to reach the primary endpoint for dogs receiving either pimobendan or benazepril in conjunction with other therapy. The primary endpoint was a composite of spontaneous cardiac death, euthanasia for cardiac reasons or withdrawal from the study due
to treatment failure. On the basis of a power calculation informed by previous studies, 260 dogs were recruited to the study, Recruitment took place at 28 centers in Europe, Canada, and Australia. Dogs were included if they had demonstrated evidence of CHF. After enrolment to the study they were randomised to receive either Pimobendan plus standard therapy or Benazepril
plus standard therapy. They were then re-evaluated
at regular intervals and followed until they reached
the study endpoint, were censored from the study for other reasons, or the study was concluded (whichever occurred  rst). Dogs receiving pimobendan plus standard therapy had a longer survival time compared to those receiving benazepril plus standard therapy.
Analysis of longitudinal QUEST trial data showed that pimobendan results in a similar quality of life for the duration of the period of treatment. However, results showed that pimobendan therapy reduced heart size (VHS, LVIDs inc and LVIDd inc) and resulted in a higher body temperature, sodium concentration, total protein and packed cell volume by comparison with benazepril. The latter 3 variables indicate less retention of free
water. Furthermore, the necessity for intensi cation of concurrent therapy in patients in the QUEST study was evaluated by looking at the time to intensi cation of therapy and the frequency of use of commonly used concurrent medications. Thus, although the average values for QoL variables were similar in the two treatment groups over the duration of the study, dogs in the benazepril group required intensi cation of treatment earlier to maintain their QoL. The similarity of QoL in
the two groups is therefore probably a consequence
of investigators being at liberty to modify concurrent medication to maintain an acceptable QoL for their patients. Thus, the results showed that the benazepril group required alteration of their therapy sooner and more frequent administration of other medications (spironolactone and digoxin) to maintain the same quality of life as dogs receiving pimobendan.
Conclusions
Clinical trials concerning pimobendan performed in dogs suggests that treatment effect and adverse side reactions depends on dose, type of underlying cardiac disease, stage of disease, and differences between species cannot be ruled out. To disregard from these differences is to oversimplify. Currently, there is convincing evidence that pimobendan prolong the pre-clinical period and extend survival times in dogs with MMVD or Dobermann Pinschers with DCM. Furthermore, pimobendan improves some quality of life variables in dogs with CHF due to DCM or MMVD, and increases survival in dogs with CHF due to MMVD.
Selected references
Boswood A. Current use of pimobendan in canine patients with heart disease. Vet Clini N Am Small Anim Pract 2010;40:571-580.
Boswood A, Haggstrom J, Gordon SG, et al. Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. J Vet Intern Med 2016;30:1765-1779.
Haggstrom J, Boswood A, O’Grady M, et al. Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study. J Vet Intern Med 2008;22:1124-1135
Pouleur H, Hanet C, Schroder E, et al. Effects of pimobendan (UD-CG 115 BS) on left ventricular inotropic state in conscious dogs and in patients with heart failure. J Cardiovasc Pharmacol 1989;14 Suppl 2:S18-22.
Summer eld NJ, Boswood A, O’Grady MR, et al. Ef cacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study). J Vet Intern Med 2012;26:1337-1349.
Suzuki S, Fukushima R, Ishikawa T, et al. The effect of pimobendan on left atrial pressure in dogs with mitral valve regurgitation. J Vet Intern Med 2011;25:1328- 1333.
An Urban Experience
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