Authors: Saud Ali Almutairi , Yazeed Mohammed Alruwaili , Hussam Mohammed Alwaily , Tariq Abdullah Alhafi , Hussam Yousef Altuwaijri , Mohammad Abdulsamad Alhamoud , Saleh Abdulaziz Alghadeer

Abstract

Background: Aspirin has traditionally been the standard antiplatelet therapy after discontinuation of dual antiplatelet therapy following percutaneous coronary intervention. However, emerging evidence suggests that clopidogrel may offer comparable or potentially better outcomes. This study compared the efficacy and safety of aspirin versus clopidogrel monotherapy in patients with coronary artery disease.

Methods: We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD420251101793). PubMed, Google Scholar, and the Cochrane Library were searched from inception to August 2025 for randomized controlled trials and observational studies comparing aspirin with clopidogrel monotherapy after dual antiplatelet therapy. Outcomes included myocardial infarction, stroke, major and minor bleeding, cardiovascular mortality, revascularization, and stent thrombosis. Risk ratios with 95% confidence intervals were pooled using a random-effects model.

Results: Seven studies involving more than 15,000 patients were included. Aspirin was associated with a significantly higher risk of stroke than clopidogrel (RR 1.51, 95% CI 1.06–2.15, P = 0.024). No significant differences were observed in myocardial infarction (RR 1.06, 95% CI 0.74–1.53, P = 0.738), major bleeding (RR 1.16, 95% CI 0.78–1.75, P = 0.463), minor bleeding (RR 1.43, 95% CI 0.72–2.82, P = 0.304), cardiovascular mortality (RR 1.14, 95% CI 0.87–1.50, P = 0.331), revascularization (RR 1.07, 95% CI 0.91–1.27, P = 0.401), or stent thrombosis (RR 1.53, 95% CI 0.81–2.89, P = 0.193).

Conclusion: Clopidogrel and aspirin showed no significant differences in most evaluated outcomes after dual antiplatelet therapy. Clopidogrel was associated with a lower risk of stroke without a significant increase in major or minor bleeding, supporting its use as an alternative to aspirin for long-term maintenance therapy.

Keywords: Coronary artery disease, clopidogrel, aspirin, percutaneous coronary intervention, dual antiplatelet therapy.