Safety and Efficacy of Ticagrelor Versus Clopidogrel in Patients Aged 70 Years or Older With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis

Older adults with acute coronary syndrome (ACS) face high risks of recurrent ischemia, mortality, and bleeding complications from antiplatelet therapy. The safety and efficacy of ticagrelor versus clopidogrel in this vulnerable population remain uncertain due to their underrepresentation in clinical trials. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, and the Cochrane Library were searched from inception to October 2025 for randomized controlled trials and cohort studies comparing ticagrelor versus clopidogrel in ACS patients aged ≥70 years. Outcomes included myocardial infarction (MI), stroke, major bleeding, all-cause death, cardiovascular (CV) death, and the composite of CV death/MI/stroke. Hazard ratios (HRs) or risk ratios with 95% confidence intervals (CIs) were pooled using random-effects models. Heterogeneity was assessed via I2 statistics. Five studies (2 randomized controlled trials and 3 cohort studies) with 22,806 participants were included. Ticagrelor significantly reduced the risk of MI (HR 0.84, 95% CI 0.75-0.95, P = 0.004) and the composite endpoint of CV death, MI, or stroke (HR 0.85, 95% CI 0.74-0.98, P < 0.05). No significant differences were found between ticagrelor and clopidogrel in stroke incidence, major bleeding, or all-cause mortality. Heterogeneity was substantial for certain outcomes, particularly bleeding and mortality. In patients aged ≥70 years with ACS, ticagrelor was associated with reduced MI and composite ischemic events compared with clopidogrel, while no statistically significant differences in bleeding events or mortality were observed. However, substantial heterogeneity and reliance on observational data for some outcomes warrant cautious clinical interpretation.