P2Y12 Inhibitor Pretreatment in Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing a Late Invasive Strategy—A Portuguese Multicenter Nationwide Registry Analysis

<b>Background/Objectives:</b> Current guidelines do not specifically address the use of P2Y12 inhibitor (P2Y12i) pretreatment in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who are expected to undergo a late invasive strategy. Nevertheless, such pretreatment may be considered in patients without a high bleeding risk (Class of Recommendation, IIb; Level of Evidence, C). Despite this ambiguity, P2Y12i pretreatment remains a common clinical practice. The present study aimed to evaluate the in-hospital prognostic impact of P2Y12i treatment prior to coronary angiography (CAG) in NSTE-ACS patients undergoing a late invasive strategy (CAG > 24 h after hospital admission). <b>Methods:</b> A retrospective analysis was conducted on NSTE-ACS patients undergoing a late invasive strategy included in the Portuguese Registry on Acute Coronary Syndromes between 2010 and 2023. The primary endpoint was a composite of in-hospital events, including all-cause mortality, non-fatal re-infarction, non-fatal stroke, and heart failure (HF). Secondary endpoints included the individual components of the primary endpoint and major bleeding (BARC types 3 and 4). <b>Results:</b> A total of 3776 patients were included (mean age, 66 ± 12 yrs; 29% female), of whom 1530 (41%) received P2Y12i pretreatment (group 1). Group 1 had a lower prevalence of prior myocardial infarction (16% vs. 21%) and prior percutaneous coronary intervention (12% vs. 15%) (both <i>p</i> ≤ 0.001). Although obstructive coronary artery disease was more frequent in group 1 (84% vs. 77%, <i>p</i> < 0.001), the presence of multivessel disease did not differ (52% vs. 52%, <i>p</i> = 0.667). Considering in-hospital antithrombotic therapy, group 1 had higher prescriptions of clopidogrel (68% vs. 56%), aspirin (99% vs. 81%), unfractionated heparin (21% vs. 8%), and enoxaparin (80% vs. 56%) (all <i>p</i> < 0.001). There was no significant difference in the primary composite endpoint between groups (9% vs. 9%, <i>p</i> = 0.906). Similarly, the secondary endpoints of all-cause mortality (0.6% vs. 0.7%), re-infarction (1.3% vs. 0.7%), stroke (0.7% vs. 0.4%), and HF (7% vs. 8%) did not differ significantly between groups (all <i>p</i> > 0.05). Nevertheless, group 1 exhibited higher rates of major bleeding (0.8 vs. 0.2%, OR 3.48, CI 95% 1.22-9.89, <i>p</i> = 0.013). <b>Conclusions:</b> Pretreatment with a P2Y12i in NSTE-ACS patients undergoing a late invasive strategy was not associated with reduction in the primary endpoint, although it was associated with higher rates of major bleeding.