Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and Methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results: At day 35, heart size had reduced in the pimobendan group:median change in (Delta) LVIDDN -0.06 (IQR:-0.15 to + 0.02), P < 0.0001, and LA:Ao -0.08 (IQR:-0.23 to + 0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in Delta LVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in Delta LA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. Conclusions and Clinical Importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study - A Randomized Clinical Trial

Background: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. Animals: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio >= 1.6, normalized left ventricular internal diameter in diastole >= 1.7, and vertebral heart sum >10.5. Methods: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. Results: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). Conclusions and Clinical Importance: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit

Evaluation of benazepril in cats with heart disease in a prospective, randomized, blinded, placebo-controlled clinical trial

© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. Background: Heart disease is an important cause of morbidity and mortality in cats, but there is limited evidence of the benefit of any medication. Hypothesis: The angiotensin-converting enzyme inhibitor benazepril would delay the time to treatment failure in cats with heart disease of various etiologies. Animals: One hundred fifty-one client-owned cats. Methods: Cats with heart disease, confirmed by echocardiography, with or without clinical signs of congestive heart failure, were recruited between 2002 and 2005 and randomized to benazepril or placebo in a prospective, multicenter, parallel-group, blinded clinical trial. Benazepril (0.5-1.0 mg/kg) or placebo was administered PO once daily for up to 2 years. The primary endpoint was treatment failure. Analyses were conducted separately for all-cause treatment failure (main analysis) and heart disease-related treatment failure (supportive analysis). Results: No benefit of benazepril versus placebo was detected for time to all-cause treatment failure (P =.42) or time to treatment failure related to heart disease (P =.21). Hazard ratios (95% confidence interval [CI]) from multivariate analysis for benazepril compared with placebo were 1.00 (0.57-1.74) for all-cause failure, and 0.99 (0.50-1.94) for forward selection and 0.93 (0.48-1.81) for bidirectional selection models for heart disease-related failure. There were no significant differences between groups over time after administration of the test articles in left atrium diameter, left ventricle wall thickness, quality of life scores, adverse events, or plasma biochemistry or hematology variables. Conclusions and Clinical Relevance: Benazepril was tolerated well in cats with heart disease, but no evidence of benefit was detected

La détermination de l'âge par scalimétrie chez le saumon atlantique (Salmo salar) dans son aire de répartition méridionale : utilisation pratique et difficultés de la méthode

Ce rapport confirme les critères d'interprétation scalimétrique utilisés pour âger le saumon atlantique en eau douce et en mer à l'aide d'exemples typiques. Il synthétise également les difficultés rencontrées pour la détermination d'âge des populations naturelles et d'élevage en les illustrant à l'aide d'exemples atypiques. Enfin, il propose un certain nombre de recommandations pour permettre une meilleure connaissance des populations de saumon atlantique dans son aire de répartition méridionale

Evaluation of benazepril in cats with heart disease in a prospective, randomized, blinded, placebo‐controlled clinical trial

International audienceBackground:Heart disease is an important cause of morbidity and mortality in cats,but there is limited evidence of the benefit of any medication. Hypothesis:The angiotensin-converting enzyme inhibitor benazepril would delaythe time to treatment failure in cats with heart disease of various etiologies. Animals:One hundred fifty-one client-owned cats. Methods:Cats with heart disease, confirmed by echocardiography, with or withoutclinical signs of congestive heart failure, were recruited between 2002 and 2005and randomized to benazepril or placebo in a prospective, multicenter, parallel-group, blinded clinical trial. Benazepril (0.5-1.0 mg/kg) or placebo was administeredPO once daily for up to 2 years. The primary endpoint was treatment failure. Ana-lyses were conducted separately for all-cause treatment failure (main analysis) andheart disease-related treatment failure (supportive analysis). Results:No benefit of benazepril versus placebo was detected for time to all-causetreatment failure (P= .42) or time to treatment failure related to heart disease(P= .21). Hazard ratios (95% confidence interval [CI]) from multivariate analysis forbenazepril compared with placebo were 1.00 (0.57-1.74) for all-cause failure, and0.99 (0.50-1.94) for forward selection and 0.93 (0.48-1.81) for bidirectional selec-tion models for heart disease-related failure. There were no significant differencesbetween groups over time after administration of the test articles in left atriumdiameter, left ventricle wall thickness, quality of life scores, adverse events, orplasma biochemistry or hematology variables. Conclusions and Clinical Relevance:Benazepril was tolerated well in cats withheart disease, but no evidence of benefit was detecte