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

Abstract

Background: Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy.Hypothesis: Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD.Animals: Two hundred and sixty client-owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia.Methods: A prospective single-blinded study with dogs randomized to PO receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure.Results: Eight dogs were excluded from analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio 5 0.688, 95% confidence limits [CL] 5 0.516-0.916, P 5 .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise.Conclusions and Clinical Importance: Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.

Use of pimobendan in 170 cats (2006–2010)

“…Increased LVIDd was associated with increased survival, which is potentially unexpected, as progressive cardiac enlargement is associated with worsening heart disease. 11,13 Increased LVWd at baseline was associated with decreased survival, which was noted in one prior study of cats with hypertrophic heart disease, 28 and this association was true for HCM cats in this study as well. Initial LA size was not related to survival in this study, despite increased LA size usually being an indicator of worse cardiac disease and prior evidence suggesting that increased LA size is predictive of decreased survival.…”

“…The primary adverse effect seen in temporal association with the advent of pimobendan administration in these cats, unusual agitation, was also seen in some canine patients in previous studies. 11,13 The other adverse effects noted may have also resulted from administration of concurrent medications. Unusual agitation was the only side effect to be tested by withdrawing pimobendan and since the agitation stopped when the pimobendan was discontinued, it may be reasonably inferred that pimobendan was the source of the agitation, although it certainly could have been coincidence.…”

Longitudinal Electrocardiographic Evaluation of Dogs with Degenerative Mitral Valve Disease

“…Previous reports describe arrhythmia frequencies between 2%19 and 26%,20 and similarly, very few of these were symptomatic. In this study, in all cases with atrial fibrillation, the arrhythmia occurred shortly before cardiac death, and only 1 of these 4 dogs was seen more than once after the onset of atrial fibrillation before dying; as dogs were followed up at 6 months intervals, this means that only 1 dog in atrial fibrillation survived for longer than 6 months.…”

Evaluation of acute congestive heart failure in dogs and cats: 145 cases (2007–2008)

“…8 Some studies have included dogs and cats with acute CHF but have not reported on this subpopulation of animals separately. [9][10][11][12][13][14] The large human databases have provided information that has enhanced the understanding of acute CHF and improved treatment of patients with this common disease. The purpose of this retrospective study was to characterize the clinical presentation, management, and in-hospital outcomes of dogs and cats diagnosed with acute CHF.…”