Research Abstract

C01 - Pharmacodynamics of Entresto® (Sacubitril/Valsartan) Versus Placebo in Dogs with Preclinical Myxomatous Mitral Valve Disease

Thursday, June 14
2:45 PM - 3:00 PM
Location: WSCC 616/617

            Angiotensin converting enzyme inhibitors (ACEi) are standard of care for treatment of congestive heart failure, but aldosterone breakthrough occurs when ACEi are used in both dogs and humans. Entresto ®, a combinational angiotensin-receptor blocker/neprilysin inhibitor, showed superiority in reducing mortality in human patients with heart failure compared to enalapril. Pharmacodynamics of Entresto ® have been evaluated in healthy dogs, showing efficacy in altering the renin-angiotensin-aldosterone system (RAAS) without causing adverse effects. The aim of this prospective, blinded, randomized, placebo-controlled study was to compare the pharmacodynamic effects of Entresto ® to placebo in dogs with preclinical myxomatous mitral valve disease (MMVD) and to evaluate the safety profile of Entresto ® in dogs with cardiac disease.

            Client-owned dogs weighing 4-15 kg with ACVIM Stage B2 MMVD were enrolled. Dogs with clinically significant pulmonary hypertension or systemic disease were excluded, as were dogs on any medication(s) known to alter the RAAS. All dogs received pimobendan throughout the study period. Each patient was evaluated at three time points (Day 0, Day 7, and Day 30). Echocardiography, thoracic radiographs (CXR), Doppler systemic arterial pressure (SAP), complete blood count, serum biochemical profile, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, and urinary aldosterone to creatinine ratio (UAldo:C) were evaluated on Day 0. On Day 0, each dog was randomly allocated to a treatment group (Entresto ®; 20 mg/kg BID) or a placebo group by the attending pharmacist. Investigators, veterinary technicians, and owners were blinded to treatment. Serum renal enzyme and electrolyte concentrations and SAP were rechecked on Day 7. Echocardiography, CXR, SAP, renal panel, plasma NT-proBNP concentration, and UAldo:C were rechecked on Day 30.

            Thirteen dogs were recruited: Entresto ® (n = 7) and placebo (n = 6). The median percent increase in UAldo:C between Day 0 and Day 30 was significantly lower in the Entresto ® group (12%; P = 0.032) as compared to the placebo group (195%). The median percent decrease of NT-proBNP concentration from Day 0 to Day 30 was not statistically different between groups (P = 0.68). No statistical differences were seen in echocardiographic, CXR, SAP, or biochemical profiles measured at any time point between groups. No adverse events were noted by the owners for dogs in either group.

            This study suggests that Entresto ® efficiently inhibits RAAS in dogs with cardiomegaly secondary to MMVD in comparison to placebo. Entresto ® is safe in regards to SAP and renal enzyme and electrolyte concentrations. No adverse effects were noted in any dog taking Entresto ®. Future studies comparing Entresto ® to ACEi, evaluating the concomitant use of diuretics and Entresto ®, and evaluating long-term (> 30 days) effects of Entresto ® are warranted.

Daniel K. Newhard, DVM

veterinarian; Cardiology resident
Auburn University College of Veterinary Medicine


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C01 - Pharmacodynamics of Entresto® (Sacubitril/Valsartan) Versus Placebo in Dogs with Preclinical Myxomatous Mitral Valve Disease


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