Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis.

Summary

Across 28,982 patients with established CAD, clopidogrel monotherapy reduced MACCE versus aspirin (HR 0.86) without increasing major bleeding or mortality over long-term follow-up. These data support preferential use of clopidogrel for secondary prevention after DAPT cessation.

Key Findings

• MACCE was lower with clopidogrel than aspirin (2.61 vs 2.99 per 100 patient-years; HR 0.86, 95% CI 0.77–0.96; p=0.0082).
• Major bleeding rates were similar between clopidogrel and aspirin (HR 0.94, 95% CI 0.74–1.21; p=0.64).
• Mortality did not differ between groups over follow-up.
• Findings were derived from seven randomized trials using one-stage IPD frailty models.

Clinical Implications

Clinicians should consider clopidogrel monotherapy as the default single antiplatelet strategy for secondary prevention in CAD patients after DAPT, especially in post-PCI or prior ACS populations.

Limitations

• Heterogeneity in trial designs and populations; not a single protocol RCT
• Some trials included initial DAPT phases; potential variability in monotherapy initiation timing

Future Directions

Head-to-head RCTs comparing clopidogrel vs aspirin in specific subgroups (e.g., diabetes, elderly, CKD) and pharmacogenomic-guided strategies (e.g., CYP2C19) could refine personalized antiplatelet monotherapy.