Potent P2Y12 Inhibitor Monotherapy vs DAPT After PCI in Patients With and Without STEMI: The NEO-MINDSET Substudy
- PMID: 41384891
- DOI: 10.1016/j.jacc.2025.10.058
Potent P2Y12 Inhibitor Monotherapy vs DAPT After PCI in Patients With and Without STEMI: The NEO-MINDSET Substudy
Abstract
Background: The effects of very early aspirin withdrawal with potent P2Y12 inhibitor monotherapy after percutaneous coronary intervention may differ based on acute coronary syndrome (ACS) presentation.
Objectives: This prespecified analysis from the NEO-MINDSET trial evaluated whether treatment effects of early aspirin discontinuation differ between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS; defined as unstable angina or non-ST-segment elevation myocardial infarction).
Methods: NEO-MINDSET randomized ACS patients to potent P2Y12 inhibitor monotherapy initiated within 4 days of hospitalization vs standard dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months. Co-primary outcomes were: 1) the composite of all-cause death, myocardial infarction, stroke, and urgent target vessel revascularization (ischemic outcome); and 2) Bleeding Academic Research Consortium types 2, 3, or 5 bleeding (bleeding outcome).
Results: Of the 3,410 participants included, 2,119 (62.1%) presented with STEMI and 1,291 (37.9%) with NSTE-ACS. Among STEMI patients, an early aspirin-free strategy was associated with a higher rate of the co-primary ischemic composite outcome compared with DAPT at 1 year (8.2% vs 5.2%, respectively; HR: 1.60; 95% CI: 1.14-2.24), whereas among those with NSTE-ACS, ischemic event rates were similar between monotherapy and DAPT (5.1% vs 6.0%, respectively; HR: 0.84; 95% CI: 0.53-1.35; P for interaction = 0.030). The co-primary bleeding outcome was lower with monotherapy than with DAPT in both STEMI (HR: 0.37; 95% CI: 0.22-0.61) and NSTE-ACS (HR: 0.45; 95% CI: 0.23-0.86) populations (P for interaction = 0.650).
Conclusions: In patients with STEMI treated with percutaneous coronary intervention, early aspirin withdrawal may be harmful, because it increases the risk of ischemic events. Conversely, in NSTE-ACS, potent P2Y12 inhibitor monotherapy may be a viable therapeutic option: Ischemic event rates were similar and bleeding was reduced compared with DAPT. (Percutaneous Coronary Intervention Followed by Antiplatelet Monotherapy in the Setting of Acute Coronary Syndromes [NEOMINDSET]; NCT04360720).
Keywords: P2Y(12) monotherapy; STEMI; aspirin-free.
Copyright © 2026. Published by Elsevier Inc.
Conflict of interest statement
Funding Support and Author Disclosures This trial was funded by Einstein Hospital Israelita with the approval and support by the Brazilian Ministry of Health through the Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde. Dr Tavares has received speaker fees from Novo Nordisk. Dr Franken has participated on an advisory board for AstraZeneca. Dr S. Lemos has been supported by a research grant provided by the DigiCardiopaTh PhD program. Dr Paolino has received speaker fees from AstraZeneca and Bayer. Dr Figueiredo has received research grants and contracts from Novo Nordisk, Intelliia, and Cytokinetics; and has received speaker fees from AstraZeneca, Bayer, Viatris, and Pfizer. Dr Santos has received honoraria related to consulting, research, and speaker activities from Amgen, Ache, Boehringer Ingelheim, Daiichi-Sankyo, Esperion, Eli Lilly, Ionis, Libbs, MSD, Novo Nordisk, Novartis, PTC Therapeutics, Torrent, Sanofi/Regeneron, and Ultragenyx. Dr Joaquim has received speaker fees from Libbs and Servier. Dr Lopes has received research grants and contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received consulting fees for AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Novo Nordisk, and Pfizer; and has performed lectures and educational activities for AstraZeneca, Daiichi-Sankyo, Novo Nordisk, and Pfizer. Dr Nicolau has received research grants and contracts from Amgen, Anthos, AstraZeneca, CSL Behring, Daiichi-Sankyo, DalCor, Esperion, Ionis, Janssen, Novartis, Novo Nordisk, Sanofi, and Vifor; and is the recipient of a scholarship from National Council of Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq; 303448/2021-0). Dr Valgimigli has received consulting fees from Abbott Vascular, Alvimedica, Biotronik, Chiesi Farmaceutici, Concept Medical, CoreFlow, Daiichi-Sankyo, Idorsia, OM Pharma, PhaseBio, Terumo, and Vesalio; and has received speaker fees from AstraZeneca, Bayer Healthcare, Boston Scientific, Medtronic, Novartis, and Vifor Pharma. Dr Angiolillo has received consulting fees and honoraria from Abbott, Amgen, Anthos, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Bio-sensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Berwanger has received research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, and Pfizer paid to his institution. Dr P.A. Lemos has consulted for Abbott Vascular, Daiichi-Sankyo, Edwards Lifesciences, and Novo Nordisk; and has had speaking engagements for B. Braun and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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