Pretreatment With P2Y₁₂ Inhibitors in Contemporary Practice: Where Do We Stand?

The management of antiplatelet strategies among patients presenting with acute coronary syndrome (ACS) continues to evolve. Earlier studies have shown ischemic benefit with P2Y₁₂ pretreatment in the setting of ACS; however, large-scale contemporary randomized trials supporting this strategy are lacking. This issue assumes relevance among patients with high bleeding risk or those referred for urgent/emergent coronary artery bypass surgery following coronary angiography. The evolution in the technology of percutaneous coronary intervention since the advent of newer-generation stents with lower risk of stent thrombosis is offset with their delivery in patients with high thrombotic and ischemic risk as the demographics of ACS shift towards the older age group. Coinciding with this shift, research has lagged on timing of administration of P2Y₁₂ inhibitors resulting in discordance in the American and European guidelines, with the latter issuing a class III recommendation (ie, harm) for routine pretreatment (defined as administration of P2Y₁₂ receptor inhibitor among patients in whom coronary anatomy is not known and an early invasive management is planned). The heterogeneity in the presentation of patients with ACS, lack of models that can predict left main or severe three-vessel disease needing urgent coronary artery bypass surgery, and shortening in the timing to angiography prompted us to review the available literature on the benefits and risks of pretreatment. With this backdrop, in this review, we synthesize the rationale for pretreatment with P2Y₁₂ inhibitors among patients presenting with ACS. For this review, articles published in English in PubMed, MEDLINE, EMBASE, and The Cochrane Library between 1980 and 2023 were reviewed. We searched for terms, P2Y₁₂ inhibitors (including clopidogrel, ticagrelor, prasugrel), pretreatment, percutaneous coronary intervention, and coronary artery bypass graft surgery. Abstracts and unpublished data were not included.