eprintid: 285338 rev_number: 17 eprint_status: archive userid: 37347 dir: disk0/00/28/53/38 datestamp: 2022-11-17 13:02:22 lastmod: 2023-05-03 08:00:30 status_changed: 2022-11-17 13:02:22 type: article metadata_visibility: show sword_depositor: 37347 creators_name: Mehran, Roxana creators_name: Steg, Philippe Gabriel creators_name: Pfeffer, Marc A. creators_name: Jering, Karola creators_name: Claggett, Brian creators_name: Lewis, Eldrin F. creators_name: Granger, Christopher creators_name: Køber, Lars creators_name: Maggioni, Aldo creators_name: Mann, Douglas L. creators_name: McMurray, John J.V. creators_name: Rouleau, Jean-Lucien creators_name: Solomon, Scott D. creators_name: Ducrocq, Gregory creators_name: Berwanger, Otavio creators_name: De Pasquale, Carmine G. creators_name: Landmesser, Ulf creators_name: Petrie, Mark creators_name: Leng, David Sim Kheng creators_name: van der Meer, Peter creators_name: Lefkowitz, Martin creators_name: Zhou, Yinong creators_name: Braunwald, Eugene creators_orcid: 0000-0002-6317-3975 creators_orcid: 0000-0002-6333-9496 title: The effects of angiotensin receptor-neprilysin inhibition on major coronary events in patients with acute myocardial infarction: insights from the PARADISE-MI trial ispublished: pub divisions: 25200000 full_text_status: public note: This work was funded by Novartis. abstract: Background: In patients who survive an acute myocardial infarction (AMI), angiotensin-converting enzyme inhibitors decrease the risk of subsequent major cardiovascular events. Whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan reduce major coronary events more effectively than angiotensin-converting enzyme inhibitors in high-risk patients with recent AMI remains unknown. We aimed to compare the effects of sacubitril/valsartan on coronary outcomes in patients with AMI. Methods: We conducted a prespecified analysis of the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitors Trial to Determine Superiority in Reducing Heart Failure Events After MI), which compared sacubitril/valsartan (97/103 mg twice daily) with ramipril (5 mg twice daily) for reducing heart failure events after myocardial infarction in 5661 patients with AMI complicated by left ventricular systolic dysfunction, pulmonary congestion, or both. In the present analysis, the prespecified composite coronary outcome was the first occurrence of death from coronary heart disease, nonfatal myocardial infarction, hospitalization for angina, or postrandomization coronary revascularization. Results: Patients were randomly assigned at a median of 4.4 [3.0–5.8] days after index AMI (ST-segment–elevation myocardial infarction 76%, non–ST-segment–elevation myocardial infarction 24%), by which time 89% of patients had undergone coronary reperfusion. Compared with ramipril, sacubitril/valsartan decreased the risk of coronary outcomes (hazard ratio, 0.86 [95% CI, 0.74–0.99], P =0.04) over a median follow-up of 22 months. Rates of the components of the composite outcomes were lower in patients on sacubitril/valsartan but were not individually significantly different. Conclusions: In survivors of an AMI with left ventricular systolic dysfunction and pulmonary congestion, sacubitril/valsartan—compared with ramipril—reduced the risk of a prespecified major coronary composite outcome. Dedicated studies are necessary to confirm this finding and elucidate its mechanism. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02924727. date: 2022-12-06 date_type: published publication: Circulation volume: 146 number: 23 publisher: American Heart Association pagerange: 1749-1757 id_number: 10.1161/CIRCULATIONAHA.122.060841 refereed: TRUE issn: 0009-7322 copyright_holders: Copyright © 2022 American Heart Association, Inc. prior: First published in Circulation 146(23):1749-1757 repro: Reproduced in accordance with the publisher copyright policy uniqueid: glaseprints:2022-285338 issn_online: 1524-4539 pubmed_id: 36321459 euro_pubmed_id: 36321459 hoa_compliant: 500 hoa_emb_len: 6 hoa_ref_pan: AB hoa_date_acc: 2022-09-22 hoa_date_pub: 2022-11-02 hoa_date_foa: 2023-01-13 hoa_version_fcd: AM hoa_exclude: FALSE hoa_gold: FALSE oa_research_materials_ack: No rioxx2_apc_input: not required citation: Mehran, R. et al. (2022) The effects of angiotensin receptor-neprilysin inhibition on major coronary events in patients with acute myocardial infarction: insights from the PARADISE-MI trial. Circulation , 146(23), pp. 1749-1757. (doi: 10.1161/CIRCULATIONAHA.122.060841 ) (PMID:36321459) document_url: https://eprints.gla.ac.uk/285338/1/285338.pdf