Effectiveness and safety of P2Y12 inhibitor pretreatment for primary PCI in STEMI: Systematic review and meta-analysis

Introduction: Dual antiplatelet therapy (DAPT) with both aspirin and P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with better outcomes. Yet, there is uncertainty regarding the optimal timing for its initiation. We performed a systematic review and meta-analysis of evidence on pretreatment with P2Y12 inhibitors in combination with aspirin in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods and results: We performed a systematic search of electronic databases Pubmed, CENTRAL, and Scopus until April 2022. Studies were eligible if they compared P2Y12 inhibitor upstream administration to downstream use in patients with STEMI submitted to PCI. Studies with patients receiving fibrinolysis or medical therapy only were excluded. Outcomes were assessed at the shortest follow-up available. Out of 2491 articles, 3 RCT and 16 non-RCT studies were included, with a total of 79300 patients (66.1% pretreated, 66.0% treated with Clopidogrel). Pretreatment was associated with reduction in definite stent thrombosis (OR 0.59 [0.37-0.94]), all-cause death (OR 0.77 [0.60-0.97]), and cardiogenic shock (OR 0.60 [0.48-0.75]). It was also associated with a lower incidence of TIMI flow <3 pre-PCI (OR 0.78 [0.67-0.92]). However, incidence of recurrent MI was not significantly reduced (OR 0.93 [0.57-1.52]). Regarding safety, pretreatment was not associated with a higher risk of major bleeding events (OR 0.83 [0.75-0.92]). Conclusion: Pretreatment with DAPT, including a P2Y12 inhibitor, was associated with better pre-PCI coronary perfusion, lower incidence of definite stent thrombosis, cardiogenic shock, and, possibly, all-cause mortality with no sign of potential harm encountered.