CLINICAL QUESTION: Does monotherapy with clopidogrel reduce the risk of major adverse cardiovascular or cerebrovascular events (MACCE) compared to monotherapy with aspirin in patients with established coronary artery disease?
BACKGROUND: Aspirin monotherapy is recommended indefinitely for patients with established coronary artery disease (CAD). However, the body of evidence supporting this treatment is based on small studies performed before the advent of modern pharmacotherapies. Previous evidence on the comparative efficacy and safety of the two antiplatelet strategies has been inconsistent and limited by the insufficient statistical power of individual trials.
STUDY DESIGN: Systematic review and meta-analysis
SETTING: Seven clinical randomized trials including patients from Asia, Europe, and North America
SYNOPSIS: 28,982 patients with established CAD were included. 14,507 were assigned to clopidogrel, and 14,475 were assigned to aspirin. The primary efficacy endpoint was a composite of MACCE, and the primary safety endpoint was major bleeding. The median follow-up was 2.3 years. One trial (n=5,438) had a follow-up of five years, and another trial (n=2,882) had a follow-up of four years. MACCE was lower in the clopidogrel group (929 events [2.61 per 100 patient-years] versus 1,062 events [2.99 per 100 patient-years]; HR, 0.86; 95% CI, 0.77 to 0.96). Major bleeding did not differ between the two groups (256 events [0.71 per 100 patient-years] versus 279 events [0.77 per 100 patient-years]; HR, 0.94; 95% CI, 0.74 to 1.21).
BOTTOM LINE: Evidence suggests that clopidogrel monotherapy is associated with greater efficacy than aspirin monotherapy for the long-term prevention of MACCE, with no associated excess risk of bleeding.
CITATION: Valgimigli M, et al. Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis. Lancet. 2025;406(10508):1091-1102. doi: 10.1016/S0140- 6736(25)01562-4.
Dr. Monteagudo is a hospitalist in the department of clinical medicine at Hospital Aleman and an instructor of internal medicine at the University of Salvador, both in Buenos Aires, Argentina.