Clopidogrel monotherapy is superior to aspirin for secondary prevention in coronary artery disease

1. Major adverse cardiovascular and cerebrovascular events were significantly reduced with clopidogrel compared to aspirin alone.

2. There was no significant difference between groups regarding risk of bleeding.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Aspirin has been recommended to be used indefinitely in patients with coronary artery disease (CAD). However, the comparative efficacy of clopidogrel versus aspirin monotherapy has not been fully evaluated. This systematic review and meta-analysis aimed to compare the efficacy and safety of clopidogrel versus aspirin in patients with CAD who had stopped or never started dual antiplatelet therapy. The primary outcome of this study was a composite of cardiovascular death, myocardial infarction, or stroke, while key secondary outcome was major bleeding. According to study results, clopidogrel monotherapy resulted in significantly fewer major adverse cardiovascular or cerebrovascular events (MACCE) compared to aspirin, without increasing the risk of bleeding. Although this study was well done, it was limited by a short follow-up period across trials.

Click to read the study in The Lancet

Relevant Reading: Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes

In-depth [systematic review and meta-analysis]: PubMed, Scopus, Web of Science, and Embase were assessed from database inception to Apr 12, 2025. Included were CAD patients who had discontinued or never started dual antiplatelet therapy and had undergone percutaneous coronary intervention or experienced acute coronary syndrome. Altogether, 28,982 patients (14,507 in clopidogrel and 14,475 in aspirin) from 7 randomized trials were included in the final analysis. The primary outcome of MACCE was significantly lower with clopidogrel monotherapy than aspirin (2.61 vs. 2.99 per 100 patient-years, hazard ratio [HR] 0.86, p=0.0082). The secondary outcome of major bleeding did not differ between clopidogrel and aspirin (0.71 vs. 0.77 per 100 patient-years, p=0.64). Findings from this study suggest that clopidogrel is more effective than aspirin for preventing MACCE, without increasing bleeding risk.

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