Comparison of the effects of ivabradine and atenolol on heart rate and echocardiographic variables of left heart function in healthy cats

Background: Ivabradine is a novel negative chronotropic drug used for treatment of ischemic heart disease in people. Little is known about its effects and safety in cats. Hypothesis/Objectives: Ivabradine is not inferior to atenolol with regard to clinical tolerance, heart rate (HR) reduction, and effects on cardiac function in healthy, lightly sedated cats. Animals: Ten healthy laboratory cats. Methods: Physical examination, systolic blood pressure measurement, and transthoracic echocardiography were performed in all cats at baseline and after oral administration (4 weeks each) of ivabradine (0.3 mg/kg q12h) and atenolol (6.25 mg/cat q12h; 1.0–1.7 mg/kg) in a prospective, double‐blind, randomized, active‐control, fully crossed study. A priori noninferiority margins for the effects of ivabradine compared with atenolol were set at 50% (f= 0.5) based on predicted clinical relevance, observer measurement variability, and in agreement with FDA guidelines. Variables were compared by use of 2‐way repeated measures ANOVA. Results: Ivabradine was clinically well tolerated with no adverse events observed. HR (ivabradine, P < .001; atenolol, P < .001; ivabradine versus atenolol, P= .721) and rate‐pressure product (RPP) (ivabradine, P < .001; atenolol, P= .001; ivabradine versus atenolol, P= .847) were not different between treatments. At the dosages used, ivabradine demonstrated more favorable effects than atenolol on echocardiographic indices of left ventricular (LV) systolic and diastolic function and left atrial performance. Conclusions and Clinical Importance: Ivabradine is not inferior to atenolol with regard to effects on HR, RPP, LV function, left atrial performance, and clinical tolerance. Clinical studies in cats with hypertrophic cardiomyopathy are needed to validate these findings.