Comparative effectiveness of ticagrelor versus clopidogrel in older adults (≥75 years) with ST-segment elevation myocardial infarction: a target trial emulation study

Background Current guidelines recommend potent P2Y12 inhibitors for patients with acute coronary syndrome to reduce ischemic events. However, elderly patients, particularly those aged 75 years or older with ST-segment elevation myocardial infarction (STEMI), have a higher risk of both thrombotic events and bleeding complications. The optimal choice of P2Y12 inhibitor in this vulnerable population remains a subject of debate, with a lack of large-scale, real-world evidence to guide clinical decision-making. Purpose This study aimed to compare the association of ticagrelor versus clopidogrel with the risks of ischemic and hemorrhagic events in patients aged ≥75 years with STEMI. Methods We conducted a retrospective, multicenter, target trial emulation study. The study included 13,884 consecutive patients aged ≥75 years diagnosed with STEMI who were treated with dual antiplatelet therapy (DAPT) consisting of aspirin plus either clopidogrel or ticagrelor. All patients were followed for at least one year. To minimize confounding, a propensity score weighting approach using overlap weights was employed. The primary endpoint was net adverse events (NACE) at one year, including ischemic events (cardiac death, recurrent myocardial infarction or ischemic stroke), hemorrhagic events (Bleeding Academic Research Consortium (BARC) classification≥3 or intracerebral hemorrhage), and cardiac death. Secondary outcomes were major adverse cerebrovascular and cardiovascular events (MACCE) including ischemic events (cardiac death, recurrent myocardial infarction or ischemic stroke) and all-cause death at one year. Results Among 13,884 eligible STEMI patients aged ≥75 years, 12,078 (87.0%) received clopidogrel and 1,806 (13.0%) received ticagrelor. In the overlap-weighted cohort, the risk of one-year NACE was significantly lower in the ticagrelor group compared with the clopidogrel group (HR: 0.852, 95% CI: 0.746-0.969, P = 0.015). The risk of one-year MACCE was also significantly lower in the ticagrelor group (HR: 0.845, 95% CI: 0.739-0.967, P = 0.014). However, there was no statistically significant difference in the risk of all-cause death at 1 year between the two groups (HR: 0.903, 95% CI: 0.772-1.055, P = 0.199). Conclusion In this target trial emulation study of patients aged ≥75 years with STEMI, the use of ticagrelor, compared with clopidogrel, was associated with a significant reduction in both NACE and MACCE at one-year follow-up, without a significant increase in all-cause mortality.