Key result
Clopidogrel monotherapy reduces MACCE ~18% versus aspirin across age groups without increasing major bleeding.
Why the study?
Emerging evidence suggests clopidogrel lowers long-term ischemic events compared with aspirin in established CAD without increasing bleeding, but it remained unclear whether these effects depend on patient age.
Does clopidogrel monotherapy reduce major adverse cardiovascular or cerebrovascular events compared to aspirin monotherapy in patients with established coronary artery disease stratified by age (≤65 vs >65 years)?
Meta-Analysis (n=28,982)
Randomized trials
Yes
Does clopidogrel monotherapy reduce major adverse cardiovascular or cerebrovascular events compared to aspirin monotherapy in patients with established coronary artery disease stratified by age (≤65 vs >65 years)?
In patients with established coronary artery disease, clopidogrel monotherapy significantly reduces major adverse cardiovascular and cerebrovascular events compared to aspirin monotherapy without increasing major bleeding, regardless of whether patients are aged ≤65 or >65 years.
Clopidogrel may be preferred over aspirin for CAD secondary prevention across ages; challenges aspirin-centric guidelines with consistent randomized evidence.
Background Aspirin monotherapy is currently recommended as the standard antiplatelet monotherapy for the secondary prevention of ischemic events in patients with established coronary artery disease (CAD). Emerging evidence suggests that, compared with aspirin, clopidogrel is associated with a lower incidence of ischemic events at long-term follow-up, without a concomitant increase in the risk of bleeding. However, it remains unclear whether these effects depend on patient age. Purpose To provide an assessment of the comparative efficacy and safety of clopidogrel versus aspirin monotherapy in patients with established CAD according to patient age. Methods The study represents a prespecified subanalysis of an individual patient data meta-analysis of 7 randomized trials in which patients were stratified according to a prespecified age cut off of 65 years. The main analysis was performed using semi-parametric shared log-normal frailty models (one-stage analysis), including a random intercept to account for differences in the baseline hazard across trials, and a random slope to account for between-trial differences in treatment effects. Secondary analyses included analyses by multivariable frailty models (multivariable one-stage analysis) and two-stage analyses. The primary efficacy endpoint was a composite of major adverse cardiovascular or cerebrovascular events (MACCE) including cardiovascular death, myocardial infarction, or stroke, assessed at the maximum available follow-up of 5.5 years. The primary safety endpoint was major bleeding at the same follow-up duration. Results A total of 13,980 patients (48.2%) were included in the ≤65 years group (median age: 57 years) and 15,002 patients (51.8%) were included in the >65 years group (median age: 74 years). Baseline characteristics were overall well balanced between treatment groups. At 5.5 years, the significant reduction in MACCE associated with clopidogrel monotherapy over aspirin monotherapy was consistent between age subgroups (≤65 years: hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.70-0.96; >65 years: HR 0.87, 95% CI 0.76-1.00), with no significant interaction (Pint=0.577). The results remained unchanged after multivariable adjustment. At 5.5 years, the absence of significant differences in major bleeding between clopidogrel and aspirin monotherapies was consistent between age subgroups (≤65 years: HR 1.03, 95% CI 0.62-1.72; >65 years: HR 0.91, 95% CI 0.72-1.14), with no significant interaction (Pint=0.). The results remained unchanged after multivariable adjustment. The two-stage analysis yielded consistent results for both MACCE and major bleeding. The effects were also consistent across all the secondary endpoints, regardless of the type of analysis. Conclusion Clopidogrel monotherapy is associated with a significant reduction in MACCE without a concomitant increase in major bleeding regardless of the patient age.MACCE
No takes yet. Share an insight, caveat, or question.
Giacoppo et al. (2026) conducted a meta-analysis in Established coronary artery disease (CAD) (n=28,982). Clopidogrel monotherapy vs. Aspirin monotherapy was evaluated on Composite of major adverse cardiovascular or cerebrovascular events (MACCE) including cardiovascular death, myocardial infarction, or stroke at 5.5 years (HR 0.82 (≤65 years); HR 0.87 (>65 years), 95% CI 0.70-0.96 (≤65 years); 0.76-1.00 (>65 years), p=0.577 for interaction). Clopidogrel monotherapy reduced MACCE vs aspirin across age groups (≤65y: HR 0.82, 95% CI 0.70-0.96; >65y: HR 0.87, 95% CI 0.76-1.00; Pint=0.577) without increasing major bleeding.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: