Comparative effectiveness and safety of dual antiplatelet therapy with ticagrelor vs. clopidogrel in older adults with acute coronary syndrome: a target trial emulation study

There is conflicting trial evidence on the comparative effects of dual antiplatelet therapy (DAPT) with ticagrelor vs. clopidogrel in older patients with acute coronary syndromes (ACS). We aimed to assess the risk of major adverse cardiovascular events (MACE) and major bleeding in ACS patients ≥75 years initiating ticagrelor vs. clopidogrel treatment.

We used healthcare data from the Stockholm region (2011–2021) to emulate a hypothetical target trial comparing ticagrelor vs. clopidogrel. MACE was defined as a composite of cardiovascular death, myocardial infarction, or stroke. Patients were followed for 12 months. Inverse probability of treatment weighting was used to adjust for 46 baseline confounders. We used weighted Cox proportional hazards regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) and the weighted Aalen–Johansen estimator to estimate absolute risks (AR).

Among 4637 older patients [median age, 81 years (IQR, 77–85)], 49% initiated DAPT with ticagrelor and 51% with clopidogrel. After weighting, all confounders were balanced. Ticagrelor was associated with a lower one-year MACE risk than clopidogrel (11.1% vs. 14.9%), corresponding to an AR difference of −3.8% (95%CI, −6.8, −0.8). The HR for ticagrelor vs. clopidogrel was 0.73 (95%CI, 0.56–0.95). There was no difference in the risk of major bleeding with one-year absolute risks of 4.3% with ticagrelor vs. 4.8% with clopidogrel, and a HR of 0.89 (95%CI, 0.63–1.27).

In ACS patients aged ≥75 years, ticagrelor was associated with a lower risk of MACE than clopidogrel. There were no differences in major bleeding, although the confidence interval was wide.