Differential Prognostic Impact of Potent P2Y ₁₂ Inhibitors in Patients With Acute Myocardial Infarction by Bleeding Risk

BACKGROUND AND OBJECTIVES: Limited data on the comparative efficacy and safety of potent P2Y₁₂ inhibitors versus clopidogrel in patients with acute myocardial infarction (AMI) stratified by bleeding risk. This study evaluated the differential prognostic impact of potent P2Y₁₂ inhibitors in patients with AMI by bleeding risk. METHODS: From the nationwide pooled registry of the Korea Acute Myocardial Infarction Registry, 1,144 propensity score-matched pairs with high bleeding risk (HBR) and 6,181 matched pairs with non-HBR were selected according to use of potent P2Y₁₂ inhibitors or clopidogrel. The primary efficacy outcome was 3-year major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, MI, repeat revascularization, stent thrombosis, or ischemic cerebrovascular accident. The primary safety outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. RESULTS: In HBR patients, the risk of MACCE was comparable between potent P2Y₁₂ inhibitors and clopidogrel (28.1% vs. 28.9%, adjusted hazard ratio [aHR], 1.00; 95% confidence interval [CI], 0.82-1.22; p=0.996). Conversely, non-HBR patients showed significantly lower risk of MACCE with potent P2Y₁₂ inhibitors (10.3% vs. 13.3%, aHR, 0.78; 95% CI, 0.69-0.88; p<0.004; p for interaction=0.016). Potent P2Y₁₂ inhibitors were associated with higher risk of bleeding in both HBR (12.4% vs. 7.6%, aHR, 1.67; 95% CI, 1.18-2.36; p=0.004) and non-HBR patients (6.5% vs. 4.3%, aHR, 1.66; 95% CI, 1.38-1.99; p<0.001; p for interaction=0.790). CONCLUSIONS: Potent P2Y₁₂ inhibitors were associated with a lower risk of MACCE only in AMI patients with non-HBR. Regardless of underlying bleeding risk, potent P2Y₁₂ inhibitors were associated with increased bleeding risk than clopidogrel.