A prospective, randomized, double‐blind, placebo‐controlled pilot study of sacubitril/valsartan (Entresto) in dogs with cardiomegaly secondary to myxomatous mitral valve disease

Abstract

BackgroundThe effects of sacubitril/valsartan (S/V) on the renin‐angiotensin‐aldosterone system (RAAS) in dogs with cardiomegaly secondary to myxomatous mitral valve disease (MMVD) are currently unknown.ObjectivesTo determine the pharmacodynamic effects of S/V on the RAAS, natriuretic peptide concentrations, systolic arterial pressure (SAP), tests of renal function, and serum electrolyte concentrations in dogs with cardiomegaly secondary to MMVD.AnimalsThirteen client‐owned dogs weighing 4‐15 kg with American College of Veterinary Internal Medicine (ACVIM) Stage B2 MMVD.MethodsProspective, randomized, double‐blind, placebo‐controlled pilot study of S/V in dogs with ACVIM Stage B2 MMVD.ResultsThirteen dogs were recruited: S/V (n = 7) and placebo (n = 6). The median percentage increase in urinary aldosterone to creatinine ratio (UAldo : C) between day 0 and day 30 was significantly lower in the S/V group (12%; P = .032) as compared with the placebo group (195%). The median percentage decrease of NT‐proBNP concentration from day 0 to day 30 was not statistically different between groups (P = .68). No statistical differences were seen in echocardiographic, thoracic radiographic, SAP, or serum biochemical test results measured at any time point between groups. No adverse events were observed for dogs in either group.Conclusion and Clinical ImportanceSacubitril/valsartan may provide a new pharmaceutical method to effectively inhibit the RAAS in dogs with ACVIM Stage B2 MMVD.

Short-Term Effects of Sacubitril/valsartan on Echocardiographic Parameters in Dogs With Symptomatic Myxomatous Mitral Valve Disease

“…Based on our results, SV at a dose of 20 mg/kg twice a day was chosen for the main study since the changes in SBP and RPP were more consistent when given to these dogs than other groups (i.e., 5 and 10 mg/kg). Interestingly, the dose of SV used in this study was also supported by a recent study in dogs with cardiomegaly secondary to MMVD ( 27 ). SV at a dose of 20 mg/kg orally was also used in a rabbit model of myocardial infarction in which it reduced mean BP at 1–2 h after treatment as well as infarct size ( 28 ).…”

The renin‐angiotensin‐aldosterone system and its suppression

“…In dogs with RAAS activation secondary to sodium restriction, Entresto (sacubitril dosed at 15 mg/kg PO q24h) led to a sustained reduction in circulating aldosterone levels when compared to dogs treated with either placebo or valsartan . This combination has also been evaluated (sacubitril dosed at 20 mg/kg PO q12h) in a small study of dogs with the American College of Veterinary Internal Medicine (ACVIM) stage B2 myxomatous mitral valve disease (MMVD) (Figure ) and was well tolerated during the 30‐day trial . Another novel therapeutic target is the ACE2 enzyme.…”

Evaluation of progression of chronic kidney disease in dogs with myxomatous mitral valve disease

“…In dogs with MMVD, the degree of increase in the circulating plasma NE levels is relative to the degree of enlargement of the heart ( 33 , 34 ). Furthermore, several studies on dogs have shown that RAAS activation may be dependent on the severity and duration of cardiac disease ( 33 , 36 , 37 ). These findings potentially account for the relatively slow progression of CKD in dogs with stage B1 MMVD, as observed in our study.…”