Timing of P2Y₁₂ Inhibitor Administration in Patients With STEMI Undergoing Primary PCI

Background: The optimal timing of P2Y₁₂ inhibitor administration in patients with ST-segment elevation myocardial infarction (STEMI) has not been completely elucidating.

Objectives: This analysis from a prospective multicenter registry sought to assess the safety and effectiveness of P2Y₁₂ inhibitor pretreatment in patients transferred for primary percutaneous coronary intervention (PCI) within a regional STEMI network.

Methods: Pretreatment was defined as P2Y₁₂ inhibitor administration before coronary angiography. Endpoints were major adverse cardiac events (MACE), major bleeding, and net adverse clinical events, a composite of MACE or major bleeding, within 30 days of index admission. Association of P2Y₁₂ inhibitor pretreatment with outcomes was modeled using doubly robust weighted estimators based on propensity score analysis.

Results: Of 1,624 patients included, 1,033 received P2Y₁₂ inhibitors before angiography and 591 in the catheterization laboratory (cath lab). The non-pretreated cohort more often had history of coronary artery disease and were more likely to receive antiplatelet therapy before the index admission. After adjustment for confounding and dependent censoring, pretreatment with P2Y₁₂ inhibitors predicted lower risk of MACE (adjusted HR: 0.53; 95% CI: 0.37-0.76), without increasing bleeding risk (adjusted HR: 0.62; 95% CI: 0.36-1.05), resulting in superior net clinical benefit (adjusted HR: 0.47; 95% CI: 0.26-0.86) compared with in-cath lab administration of P2Y₁₂ inhibitors. There was a significant treatment-by-time interaction for MACE risk, whereby the observed benefits of pretreatment only became apparent when time between P2Y₁₂ inhibitor administration and PCI was longer than 80 minutes.

Conclusions: In contemporary patients with STEMI transferred for primary PCI, pretreatment with P2Y₁₂ inhibitors was associated with a significant time-dependent reduction of 30-day MACE without increasing bleeding risk.