The effect of neprilysin inhibition on left ventricular remodeling in patients with asymptomatic left ventricular systolic dysfunction late after myocardial infarction

Docherty, K. F. et al. (2021) The effect of neprilysin inhibition on left ventricular remodeling in patients with asymptomatic left ventricular systolic dysfunction late after myocardial infarction. Circulation, 144(3), pp. 199-209. (doi: 10.1161/CIRCULATIONAHA.121.054892) (PMID:33983794)

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Background: Patients with left ventricular systolic dysfunction (LVSD) following myocardial infarction (MI) are at high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system (RAS) inhibition may result in greater attenuation of adverse LV remodeling due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic and sympatholytic effects. Methods: We performed a prospective, multi-center, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103mg twice daily with valsartan 160mg twice daily in patients ≥3 months following MI with a LV ejection fraction (LVEF) ≤40% who were taking a RAS inhibitor (equivalent dose of ramipril ≥2.5mg twice daily), and a beta-blocker unless contraindicated or intolerant. Patients in New York Heart Association functional classification ≥II or with signs and symptoms of HF were excluded. The primary outcome was change from baseline to 52-weeks in LV end-systolic volume index (LVESVI) measured using cardiac magnetic resonance imaging (MRI). Secondary outcomes included other MRI measurements of LV remodeling, change in N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-TnI), and a patient global assessment of change questionnaire. Results: From July 2018 to June 2019, 93 patients were randomized: mean age 60.7±10.4 years, median time from MI 3.6 years (IQR 1.2-7.2), mean LVEF 36.8%±7.1, median NT-proBNP 230pg/mL (124-404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LVESVI; adjusted between-group difference -1.9mL/m2 (95%CI -4.9, 1.0); p=0.19. There were no significant between-group differences in NT-proBNP, hs-TnI, LV end-diastolic volume index, left atrial volume index, LVEF, LV mass index, or patient global assessment of change. Conclusions: In patients with asymptomatic LVSD following MI, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Clinical Trial Registration: URL: Unique identifier: NCT03552575

Item Type:Articles
Glasgow Author(s) Enlighten ID:Squire, Dr Iain and Stanley, Miss Bethany and McConnachie, Professor Alex and Lee, Matthew and Docherty, Dr Kieran and Welsh, Professor Paul and Petrie, Professor Mark and Campbell, Dr Ross and McMurray, Professor John and Brooksbank, Dr Katriona and Jackson, Dr Alice and Hopkins, Mrs Tracey and Jhund, Professor Pardeep and Roditi, Dr Giles
Authors: Docherty, K. F., Campbell, R. T., Brooksbank, K. J.M., Dreisbach, J. G., Forsyth, P., Godeseth, R., Hopkins, T., Jackson, A. M., Lee, M. M.Y., McConnachie, A., Roditi, G., Squire, I. B., Stanley, B., Welsh, P., Jhund, P. S., Petrie, M., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:Circulation
Publisher:American Heart Association
ISSN (Online):1524-4539
Published Online:13 May 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Circulation 144(3): 199-209
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
300857Effect of sacubitril/valsartan compared to valsartan on left ventricular remodelling in patients with asymptomatic left ventricular systolic dysfunction after myocardial infarctionJohn McMurrayBritish Heart Foundation (BHF)PG/17/23/32850CAMS - Cardiovascular Science
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science