Therapeutic Evaluation of Sacubitril-valsartan (Arni) in Canine Dilated Cardiomyopathy

Canine dilated cardiomyopathy (DCM) is one of the commonly diagnosed acquired myocardial disease in dogs characterized by hypokinesis, eccentric myocardial hypertrophy. Activation of neurohumoral system (i.e., sympathetic and RAAS) is crucial in the pathogenesis of DCM with deteriorative effect on the failing heart. In current protocol, ACE inhibitors are being employed to counter RAAS through blocking of ACE pathway, however aldosterone breakthrough due to alternate tissue pathway render the treatment less effective. The natriuretic peptides (viz., ANP, BNP) produced in response to cardiac wall stress have beneficial natriuretic, diuretic and suppressed cardiac sympathetic effects, however, will be cleaved by the enzyme neprilysin limiting their activity. With this background, this study was aimed to study the effect of Sacubitril-Valsartan, an ARNi drug in management of canine heart failure due to DCM, evaluating its effects on clinical, echocardiographic parameters as well as on RAAS and natriuretic peptides.

Dogs with confirmed DCM on echocardiography were randomly divided into two treatment groups, one with conventional protocol having ACEI (Group II) and another group with ARNi replacing ACEI in the protocol (Group III). Clinical signs, ECG, echocardiographic evaluation was done at monthly interval till 90^th day of therapy. Radiographic evaluation as well as effect on RAAS by assessing plasma natriuretic peptides and urine aldosterone-creatinine ratio was done on 0^th day and 90^th days of therapy. Data was analysed using ANOVA and independent ‘t’ test followed by LSD using IBM SPSS version 2.0.

In the study, group III dogs showed early resolution of clinical signs compared to group II. Group III showed a significant decrease in left atrial diameter and LA/Ao ratio earlier by 30^th day of therapy, while in Group II, the same was noticed on the 60^th day. Cardiac internal diameters were found to be significantly decreased in group III while group II showed a non-significant decrease. Systolic function was found to be significantly increased by 30^th day in group III while group III has a non significant increase in ejection fraction. Significant decline of Uald:cre ratio was noticed in group III indicating its effective inhibition of RAAS. In the study dogs treated with sacubitril-valsartan was found to have faster resolution of clinical signs, greater reduction in cardiac dimensions and improvement in systolic function compared to ACEI treated dogs.