Ticagrelor versus Clopidogrel in Acute Coronary Syndrome Patients with High Ischemic and Bleeding Risk after Drug-eluting Stent Implantation

Patients with acute coronary syndrome (ACS) who have concurrent high ischemic and high bleeding risk are common after percutaneous coronary intervention (PCI), yet evidence guiding P2Y12 inhibitor selection remains limited. We compared ticagrelor and clopidogrel in ACS patients meeting OPT-BIRISK dual high-risk criteria after drug-eluting stent (DES) implantation. We retrospectively analyzed a single-center PCI registry. ACS patients undergoing new-generation DES implantation (March 2019–March 2022) who met both high ischemic and high bleeding risk criteria were classified by discharge P2Y12 inhibitor. Propensity score overlap weighting was adjusted for confounding. The primary endpoint was 12-month net adverse clinical events (NACE): all-cause death, myocardial infarction, stroke, or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The final cohort comprised 20,213 dual high-risk patients (ticagrelor, 4,563 [22.6%]; clopidogrel, 15,650 [77.4%]). NACE was similar between groups (4.58% vs. 5.21%; adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 0.89–1.23; p = 0.568). Ticagrelor was not associated with reduced ischemic events (aHR, 0.90; 95% CI, 0.72–1.12; p = 0.333) but with higher BARC type 3 or 5 bleeding (2.17% vs. 1.57%; aHR, 1.39; 95% CI, 1.08–1.77; p = 0.009). In exploratory subgroup analysis, ticagrelor was associated with higher NACE in patients aged 75 years or older (p-Value for interaction = 0.04). In dual high-risk ACS patients undergoing DES implantation, discharge ticagrelor-based dual antiplatelet therapy was associated with higher bleeding risk without reducing NACE or ischemic events compared with clopidogrel. These observational findings support individualized P2Y12 inhibitor selection and warrant prospective confirmation.