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Multicenter Study
. 2020 Feb:27:34-53.
doi: 10.1016/j.jvc.2019.12.002. Epub 2020 Jan 10.

DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study

M Borgarelli  1 , L Ferasin  2 , K Lamb  3 , C Bussadori  4 , D Chiavegato  5 , G D'Agnolo  6 , F Migliorini  7 , M Poggi  8 , R A Santilli  9 , E Guillot  10 , C Garelli-Paar  10 , R Toschi Corneliani  11 , F Farina  12 , A Zani  13 , M Dirven  14 , P Smets  14 , C Guglielmini  15 , P Oliveira  16 , M Di Marcello  17 , F Porciello  18 , S Crosara  19 , P Ciaramella  20 , D Piantedosi  20 , S Smith  21 , S Vannini  4 , E Dall'Aglio  22 , P Savarino  23 , C Quintavalla  24 , M Patteson  25 , J Silva  4 , C Locatelli  26 , M Baron Toaldo  27
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Free article
Multicenter Study

DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study

M Borgarelli et al. J Vet Cardiol. 2020 Feb.
Free article

Abstract

Introduction: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial.

Hypothesis: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI).

Animals: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) ≥1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) ≥1.7.

Methods: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations.

Results: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group.

Conclusions: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance.

Keywords: Dog; Heart; Heart failure; NT-proBNP; Therapy.

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