Ticagrelor vs. clopidogrel in elderly patients following acute myocardial infarction: a multicenter international analysis

Abstract Background/Introduction Acute coronary syndrome (ACS) is common among elderly patients and is associated with a high risk of complications. Managing ACS, particularly dual antiplatelet therapy (DAPT), poses challenges due to the increased risk of recurrent hemorrhagic and ischemic events in this population. Purpose This study evaluated cardiovascular outcomes in patients ≥75 years that were initiated on DAPT with aspirin (ASA) plus either ticagrelor or clopidogrel following an acute myocardial infarction (AMI). Methods We used the TriNetX repository to identify adult patients (≥75 years) diagnosed with AMI between January 1, 2011, and December 31, 2021, who subsequently initiated DAPT and were not on anticoagulation. Patients were stratified into two cohorts: ASA + ticagrelor and ASA + clopidogrel. Outcomes assessed included major bleeding, repeat coronary intervention, all-cause mortality, all-cause hospitalizations, stroke, new-onset atrial fibrillation, and pacemaker implantation. Follow-up time was restricted to one year. A 1:1 propensity score matching algorithm was applied using the greedy nearest-neighbor method with a caliper of 0.1 pooled standard deviations to ensure balance (i.e., comorbidities, medications, laboratory values) between the two cohorts. Logistic regression models were used to calculate adjusted odds ratios (aOR), and Cox proportional hazards models estimated hazard ratios (HR). Results Before propensity score matching (PSM), 19,859 patients were in the ASA + ticagrelor cohort, and 47,032 were in the ASA + clopidogrel cohort. Post-PSM, 19,746 patients remained in each cohort, with a mean age of 82.2 years and a mean follow-up duration of 298.77 days for the ASA + ticagrelor cohort and 297.59 days for the ASA + clopidogrel cohort. The ASA + ticagrelor cohort had a higher incidence of major bleeding (aOR 1.19 95% CI, 1.08–1.31) and pacemaker implantation (aOR 1.14 95% CI, 1.02–1.29) compared to the ASA + clopidogrel cohort. Event-free survival analysis showed lower survival rates for major bleeding (HR 1.18 95% CI, 1.07–1.30) and pacemaker implantation (HR 1.14 95% CI, 1.01–1.28). No significant differences were observed between cohorts in repeat coronary interventions (aOR 0.95 95% CI, 0.88–1.03), atrial fibrillation (aOR 1.03 95% CI, 0.97–1.08), all-cause mortality (aOR 1.03 95% CI, 0.96–1.12), all-cause hospitalization (aOR 1.01 95% CI, 0.97–1.05), or stroke (aOR 0.95 95% CI, 0.86–1.04). Conclusions In elderly patients, DAPT with ASA + ticagrelor was associated with higher rates of major bleeding and need for pacemaker compared to ASA + clopidogrel. Given the similar risks of recurrent coronary intervention and mortality between the two regimens, these findings highlight the need for careful consideration when selecting ticagrelor over clopidogrel in this population.