Impact of P2Y₁₂ Inhibitor Pretreatment on Clinical Outcomes in ST‐Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Retrospective Cohort Study

ABSTRACT Background The benefit of P2Y₁₂ inhibitor pretreatment before primary percutaneous coronary intervention (PCI) in ST‐segment elevation myocardial infarction (STEMI) remains uncertain. Aims This study examined the association between pretreatment and short‐ and long‐term cardiovascular outcomes. Methods In this retrospective cohort study, adults (≥ 18 years) hospitalized for STEMI and undergoing PCI were identified from the TriNetX US Collaborative Network (January 2010 to December 2024). Patients receiving P2Y₁₂ inhibitors before PCI ( n = 72,913) were matched 1:1 by propensity score to those without pretreatment ( n = 66,450), yielding 21,689 patients per group. Primary endpoints at 1 month and 1 year included all‐cause mortality, major adverse cardiovascular events (MACE), stent thrombosis, and stent restenosis. Multivariable Cox regression provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Results After matching, baseline characteristics were balanced (all standardized mean differences < 0.10). At 1 month, pretreatment was associated with higher all‐cause mortality (4.5% vs. 4.0%; RR 1.13; p = 0.007), MACE (8.7% vs. 7.5%; RR 1.16; p < 0.001), stent thrombosis (1.9% vs. 0.8%; RR 2.39; p < 0.001), and stent restenosis (5.3% vs. 4.0%; RR 1.32; p < 0.001). These differences persisted at 1 year (mortality 10.2% vs. 9.0%; RR 1.14; p < 0.001; MACE 18.9% vs. 18.2%; RR 1.04; p < 0.001; thrombosis 2.4% vs. 1.1%; RR 2.26; p < 0.001; restenosis 11.0% vs. 9.6%; RR 1.14; p < 0.001). Secondary endpoints showed no differences in major bleeding or cardiac arrest, while ischemic stroke was lower at 1 month and MI recurrence was reduced at 6 months and 1 year. In Cox models, pretreatment predicted higher 1‐year hazards for mortality, MACE, and restenosis, and a threefold increase in 1‐month stent thrombosis. Conclusion In this retrospective, non‐randomized analysis of administrative data from the TriNetX database, P2Y₁₂ inhibitor pretreatment before PCI in STEMI was linked to modestly increased 1‐year risks of mortality, MACE, and restenosis, and markedly higher 1‐month stent thrombosis, highlighting the need for prospective trials to optimize antiplatelet strategies.