Ticagrelor versus clopidogrel in acute coronary syndrome patients with concurrent high ischemic and bleeding risk after drug-eluting stent implantation

Background Patients with acute coronary syndrome (ACS) who have concurrent high ischemic and high bleeding risk represent a common but understudied group after percutaneous coronary intervention. Evidence guiding P2Y₁₂ inhibitor selection in this setting remains limited. This study compared ticagrelor and clopidogrel in ACS patients meeting OPT-BIRISK dual high-risk criteria after drug-eluting stent implantation. Methods In this retrospective analysis of a single-center, real-world PCI registry, patients with ACS undergoing new-generation drug-eluting stent (DES) implantation between March 2019 and March 2022 were included. Patients meeting both high ischemic risk and high bleeding risk criteria according to the OPT-BIRISK standard were identified and classified by P2Y₁₂ inhibitor prescribed at discharge. Propensity score overlap weighting adjusted for confounding. The primary endpoint was net adverse clinical events (NACE), a composite of all-cause death, myocardial infarction, stroke, or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 12 months. Results Of 30,562 ACS patients, 22,012 (72.0%) met dual high-risk criteria. The final cohort comprised 20,213 patients (ticagrelor, 4,563 [22.6%]; clopidogrel, 15,650 [77.4%]). NACE risk was similar between groups (4.58% vs 5.21%; adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 0.89 to 1.23; P = 0.568). Ticagrelor was not associated with a significant reduction in ischemic events (aHR, 0.90; 95% CI, 0.72 to 1.12; P = 0.333), but was associated with a higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (2.17% vs 1.57%; aHR, 1.39; 95% CI, 1.08 to 1.77; P = 0.009). In exploratory subgroup analysis, ticagrelor was associated with higher net adverse clinical events in patients aged 75 years or older (P for interaction = 0.04). Conclusions In ACS patients with concurrent high ischemic and high bleeding risk undergoing drug-eluting stent implantation, discharge ticagrelor-based dual antiplatelet therapy was associated with higher bleeding risk without a significant reduction in NACE or ischemic events compared with clopidogrel. These observational findings support individualized P2Y₁₂ inhibitor selection and warrant prospective confirmation.