Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST)

Abstract Background The renin‐angiotensin‐aldosterone system (RAAS), when chronically activated, is harmful and RAAS‐suppressive drugs are beneficial in the treatment of congestive heart failure (CHF). Mineralocorticoid receptor antagonists are widely used in the treatment of CHF in people. Hypothesis/Objectives To determine if a mineralocorticoid receptor antagonist (spironolactone) is beneficial and safe in CHF due to myxomatous mitral valve disease (MMVD) of varying severity, we hypothesized that, when combined with furosemide, a combination product (S+BNZ) containing the ACE inhibitor (ACE‐I), benazepril, and spironolactone, would be superior to benazepril alone. Animals Five hundred and sixty‐nine client‐owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10‐days' duration. Methods After initial stabilization, dogs were randomized into a positive‐controlled, double‐blind, multicenter trial, to receive furosemide plus S+BNZ or furosemide plus benazepril. The primary outcome variable was the percentage of dogs reaching cardiac endpoint before Day 360. Cardiac endpoint was defined as cardiac death or euthanasia, recurrence of pulmonary edema, necessity for nonauthorized cardiac drug(s) or a furosemide dosage >8 mg/kg/d. Results A significantly lower percentage of dogs treated with S+BNZ reached the primary outcome variable by Day 360 (OR = 0.56; 95% CI, 0.32‐0.98; P = .04) and risk of dying or worsening from cardiac causes, was significantly reduced (HR = 0.73; 95% CI = 0.59‐0.89, P = .002) vs benazepril alone. Adverse events, potentially associated with treatment, were rare and equal between groups. Conclusion and Clinical Importance The combination of S+BNZ is effective, safe, and superior to benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF caused by MMVD in dogs.