Timing of P2Y12 inhibitor administration in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention: a meta-analysis

Background The optimal timing of P2Y12 inhibitor administration in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) remains controversial. While early pretreatment at first medical contact may reduce ischemic complications, concerns persist regarding bleeding risk and uncertain impact on mortality. Purpose To evaluate the clinical impact of P2Y12 pretreatment compared with periprocedural administration in patients with STEMI undergoing PCI. Methods A systematic literature search was conducted using PubMed, Scopus, and Cochrane databases to identify eligible studies comparing P2Y12 inhibitor administration at first medical contact versus in the catheterization laboratory. The primary outcomes were in-hospital and 30-day all-cause mortality and major adverse cardiovascular events (MACE). Secondary clinical endpoints included in-hospital and 30-day myocardial infarction, stent thrombosis, and major bleeding events. Additional procedural endpoints included TIMI flow before and after PCI, thrombus aspiration, and no-reflow phenomenon. Random-effects meta-analyses were performed, and effect estimates were expressed as risk ratios (RR) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results Twenty-three studies comprising 83,955 patients were included in the meta-analysis. P2Y12 pretreatment was associated with lower rates of both in-hospital (RR: 0.78, 95%CI: 0.67-0.89, I²=0%) and 30-day MACE (RR: 0.82, 95%CI: 0.75-0.88, I²=19%). Conversely, there was no difference regarding in-hospital (RR: 0.74, 95%CI: 0.52-1.05, I²=59%) and 30-day all-cause mortality (RR: 0.81, 95%CI: 0.63-1.04, I²=59%). In addition, P2Y12 pretreatment was associated with a reduced risk of myocardial infarction (RR 0.85, 95% CI 0.74–0.98; I²=0%) and stent thrombosis (RR 0.65, 95% CI 0.42–0.99; I²=31%) at 30 days, without a significant difference in major bleeding risk (RR 0.97, 95% CI 0.84–1.12; I²=14%). No significant difference was observed in in-hospital myocardial infarction or stent thrombosis. Procedural outcomes, including initial TIMI 0/1 flow (RR 0.95, 95% CI 0.89–1.01; I²=14%), post-procedural TIMI 3 flow (RR 1.02, 95% CI 1.00–1.05; I²=69%), thrombus aspiration (RR: 1.04, 95%CI: 0.89-1.21, I²=85%), and no-reflow phenomenon (RR: 0.84, 95%CI: 0.64-1.11, I²=39%), were similar between groups. Conclusion P2Y12 inhibitor pretreatment in patients with STEMI undergoing PCI was associated with a significant reduction in early ischemic events, including MACE, myocardial infarction, and stent thrombosis, without an increase in major bleeding. However, no mortality benefit was observed. These findings suggest a potential advantage of early antiplatelet loading in selected patients, while underscoring the need for additional randomized trials.