Ischemic and bleeding outcomes of potent P2Y12 inhibitor antiplatelet agents versus clopidogrel in elderly patients with acute coronary syndrome: A meta-analysis of randomized trials

Background: The role of P2Y12 inhibition in acute coronary syndrome (ACS) has been well described in literature. However, the agent of choice is less clear among elderly patients (>65 years) who are at increased risk of bleeding. This meta-analysis was designed to investigate the efficacy and safety of potent P2Y12 inhibitors vs. clopidogrel in this population. Methods and results: PubMed, Cochrane Central Register of Clinical Trials, EMBASE, and ClinicalTrial.gov (inception through February 25, 2021) were searched for randomized studies comparing potent oral P2Y12 inhibitors to clopidogrel in elderly population presenting with ACS. Study endpoints included major adverse cardiac events (MACE), major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) were computed and p<0.05 was considered significant. Eight randomized studies with a total 10,081 patients were included in the final analysis. At mean follow up of 26 months, there were no significant differences between potent oral P2Y12 inhibitors and clopidogrel in MACE (HR 0.97, 95% CI [0.82–1.15]; p=0.73), all-cause mortality (HR 0.91, 95% CI [0.75–1.10]; p=1.00), MI (HR 0.95, 95% CI [0.78–1.17]; p=0.64), and stroke (HR 1.24, 95% CI [0.82–1.86]; p=0.31). However, potent oral P2Y₁₂ inhibitors were associated with a reduction in cardiovascular mortality (HR 0.82, 95% CI [0.68–0.98]; p=0.03), and an increase in major bleeding events (HR 1.32, 95% CI [1.09–1.59]; p<0.01). Conclusion: In comparison with clopidogrel, the use of potent oral P2Y12 inhibitors in elderly patients with ACS, is associated with a reduction in the risk of cardiovascular mortality with increased risk of bleeding events and no significant change in MACE outcomes.