Pharmaceutical Innovation & Development, Ceva Animal Health, Lenexa, Kansas, USA.
Companion Animal Franchise, Ceva Santé Animale, Libourne, France.
J Vet Intern Med. 2021 Jul;35(4):1673-1687. doi: 10.1111/jvim.16155. Epub 2021 May 24.
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.
Five hundred and sixty-nine client-owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10-days' duration.
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.
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.
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.
肾素-血管紧张素-醛固酮系统（RAAS）在慢性激活时是有害的，而 RAAS 抑制药物在充血性心力衰竭（CHF）的治疗中是有益的。醛固酮受体拮抗剂在心力衰竭患者中被广泛用于治疗心力衰竭。
假设/目的：为了确定醛固酮受体拮抗剂（螺内酯）是否对由粘液样二尖瓣疾病（MMVD）引起的不同严重程度的 CHF 有益且安全，我们假设当与呋塞米联合使用时，包含 ACEI（贝那普利）和螺内酯的组合产品（S+BNZ）将优于贝那普利单药治疗。
569 只患有 MMVD 和 CHF（ACVIM 分期 C）且病程不超过 10 天的客户拥有的狗。
在初始稳定后，狗被随机分配到一项阳性对照、双盲、多中心试验中，接受呋塞米加 S+BNZ 或呋塞米加贝那普利治疗。主要结局变量是在第 360 天前达到心脏终点的狗的百分比。心脏终点定义为心脏死亡或安乐死、肺水肿复发、需要未经授权的心脏药物或呋塞米剂量>8mg/kg/d。
接受 S+BNZ 治疗的狗在第 360 天达到主要结局变量的百分比显著降低（OR=0.56；95%CI，0.32-0.98；P=0.04），死于或因心脏原因恶化的风险显著降低（HR=0.73；95%CI=0.59-0.89，P=0.002），与贝那普利单药治疗相比。与治疗相关的不良反应很少，两组之间相等。
当与呋塞米联合使用时，S+BNZ 联合治疗对于管理由 MMVD 引起的轻度、中度或重度 CHF 是有效、安全的，优于贝那普利单药治疗。
