Impact of sacubitril/valsartan compared to ramipril on cardiac structure and function following acute myocardial infarction: The PARADISE-MI echocardiographic sub-study

Shah, A. M. et al. (2022) Impact of sacubitril/valsartan compared to ramipril on cardiac structure and function following acute myocardial infarction: The PARADISE-MI echocardiographic sub-study. Circulation, 146(14), pp. 1067-1081. (doi: 10.1161/CIRCULATIONAHA.122.059210) (PMID:36082663)

Abstract

BACKGROUND: Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI. METHODS: In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes. RESULTS: Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF (P=0.79) or LAV (P =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume (P=0.025) and greater decline in LV mass index (P=0.037), increase in tissue Doppler e’lat (P=0.005), decrease in E/e’lat (P=0.045), and decrease in tricuspid regurgitation peak velocity (P=0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure. CONCLUSIONS: Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort.

• Item Type: Articles
• Additional Information: The PARADISE-MI trial was funded by Novartis. Dr Shah was also supported by National Institutes of Health/National Heart, Lung, and Blood Institute grants R01HL135008, R01HL143224, R01HL150342, R01HL148218, R01HL160025, and K24HL152008. Dr Nicolau is recipient of a scholarship from Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (Na-tional Council for Scientific and Technological Development), Brazil (CNPq No. 301242/2017-8).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jhund, Professor Pardeep and Kober, Professor Lars
• Authors: Shah, A. M., Claggett, B., Prasad, N., Li, G., Volquez, M., Jering, K., Cikes, M., Kovacs, A., Mullens, W., Nicolau, J. C., Køber, L., van der Meer, P., Jhund, P. S., Ibram, G., Lefkowitz, M., Zhou, Y., Solomon, S. D., and Pfeffer, M. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Circulation
• Publisher: American Heart Association
• ISSN: 0009-7322
• ISSN (Online): 1524-4539
• Published Online: 09 September 2022
• Copyright Holders: Copyright © 2022 American Heart Association, Inc.
• First Published: First published in Circulation 146(14): 1067-1081
• Publisher Policy: Reproduced in accordance with the publisher copyright policy