Effect of cilobradine in cats with a first episode of congestive heart failure due to primary cardiomyopathy.

INTRODUCTION: Heart rate (HR) is often elevated in cats with cardiomyopathies (CMPs). Pharmacologic modulation of HR may reduce cardiac morbidity and mortality. OBJECTIVES: To investigate the effects of cilobradine vs. placebo, regarding time to cardiac mortality or morbidity in cats with first episode of congestive heart failure (CHF) due to primary CMP. ANIMALS: Three hundred and sixty-seven client-owned cats with primary CMP that had presented with a first episode of CHF at 50 centers in Europe. Per-protocol population comprised 193 cats (n = 89 cilobradine, n = 104 placebo). An interim analysis for futility was planned. METHODS: Prospective, randomized, placebo-controlled, double-blinded, multicenter clinical trial. Primary outcome variable was the time to a composite of cardiac mortality or cardiac morbidity. RESULTS: Median time to primary outcome was 84 days (95% confidence interval [CI]: 63-219 days) in the cilobradine group (CG) and 203 days in the placebo group (95% CI: 145-377 days) with observed hazard ratio of 1.44, indicating a higher hazard for the CG (P = 0.057). Mean HR was 28 beats per minute (bpm) lower at Day 7 (P < 0.0001) and remained 29 bpm lower at Day 360 (P = 0.026) in the CG than that in the placebo group. Although the number of adverse events did not differ, there were more serious adverse events in the CG. CONCLUSIONS: Heart rate reduction by cilobradine in cats with a first episode of CHF due to primary CMP did not reduce cardiac mortality and morbidity.

Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.

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.

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 = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .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.