Impact of P2Y12 inhibitor pretreatment on periprocedural (type 4a) myocardial infarction and bleeding in NSTEMI

Introduction and objectives: Although widely used in clinical practice, pretreatment with a P2Y12 inhibitor in patients with non–ST-segment elevation myocardial infarction (NSTEMI) remains controversial and is not recommended by current guidelines. This study aimed to evaluate the impact of P2Y12 inhibitor pretreatment on the incidence of periprocedural (type 4a) myocardial infarction (MI) and in-hospital bleeding in NSTEMI patients undergoing percutaneous coronary intervention (PCI). Methods: Consecutive NSTEMI patients undergoing PCI were enrolled from the AMIPE multicenter registry (NCT03883711) and stratified based on pretreatment strategy according to European Society of Cardiology (ESC) guideline timelines. Patients whose P2Y12 inhibitor administration did not comply with contemporaneous ESC recommendations were excluded. The analysis compared patients treated before and after the 2020 ESC recommendation against routine pretreatment. The primary efficacy endpoint was type 4a MI, and the primary safety endpoint was in-hospital bleeding defined as Bleeding Academic Research Consortium (BARC) types 2, 3, and 5. Results: A total of 1254 patients were included, of whom 740 (59.0%) received pretreatment, mainly with clopidogrel (91.2%). Type 4a MI occurred in 15.2% of patients, with no significant difference between the pretreatment and no pretreatment groups (15.9% vs 14.2%; aOR, 1.08; P = .638). In contrast, in-hospital bleeding was significantly higher in the pretreatment group (7.7% vs 3.9%; aOR, 2.17; P = .005), mainly due to BARC type 2 events. Conclusions: In NSTEMI patients undergoing PCI, pretreatment with P2Y12 inhibitors, mainly clopidogrel, did not reduce the incidence of type 4a MI but was associated with an increased risk of in-hospital bleeding. © 2025 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Impacto del pretratamiento con inhibidores del receptor P2Y12 sobre el infarto de miocardio periprocedimental (tipo 4a) y la hemorragia en el IAMSEST Palabras clave: Infarto agudo de miocardio sin elevación del segmento ST Inhibidores de P2Y12 Tratamiento antiagregante plaquetario doble R E S U M E N Introducción y objetivos: Aunque aún frecuente en la práctica, el pretratamiento con un inhibidor del receptor P2Y12 en pacientes con infarto agudo de miocardio sin elevación del segmento ST (IAMSEST) sigue siendo controvertido y las guías actuales no lo recomiendan. Este estudio evaluó el impacto del pretratamiento con inhibidores P2Y12 sobre la incidencia del infarto de miocardio (IM) periprocedi- * Corresponding author. E-mail address: [email protected] (C. Pizzi). ◊ The first two authors contributed equally to this work. A U T O M A T E D _ P R I N T = t r u e https://doi.org/10.1016/j.rec.2025.12.002 1885-5857/© 2025 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). Please cite this article in press as: Armillotta M, et al. Impact of P2Y12 inhibitor pretreatment on periprocedural (type 4a) myocardial infarction and bleeding in NSTEMI. Rev Esp Cardiol. 2026. https://doi.org/10.1016/j.rec.2025.12.002