Comparative efficacy of clopidogrel and aspirin monotherapy after dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis
N Ktenopoulos, K Karampinos, A Apostolos, P Vlachakis, I Kachrimanidis, T Theodoropoulou, N Tsiamis, L Koliastasis, S Tsalamandris, M Drakopoulou, A Synetos, G Latsios, K Tsioufis, K ToutouzasAbstract
Background
Optimal long-term antiplatelet monotherapy following percutaneous coronary intervention (PCI) remains debated, with aspirin traditionally recommended despite emerging evidence supporting P2Y12 inhibitor monotherapy.
Purpose
The comparison of clinical outcomes between clopidogrel and aspirin monotherapy in patients following PCI.
Methods
Our systematic review and meta-analysis was performed in accordance with the updated PRISMA guidelines. We conducted an electronic bibliographic screening in the three major databases of the literature (Cochrane, Medline and Scopus), to identify relevant studies published up to February 15th, 2026. The primary endpoint was major adverse cardiovascular events (MACE). Secondary endpoints included all-cause and cardiac mortality, myocardial infarction (MI), ischemic and haemorrhagic stroke, major bleeding, repeat revascularization, target vessel revascularization and stent thrombosis. Relative risks (RR) with 95% confidence intervals (CI) were calculated and pooled using random-effects models.
Results
A total of 164,361 post-PCI patients were included (clopidogrel: 81,869, aspirin: 82,492). Clopidogrel monotherapy was associated with a significantly lower risk of MACE compared to aspirin (RR 0.78, 95% CI 0.69-0.88, I²=54%). No significant differences were observed in all-cause mortality (RR 0.90, 95% CI 0.59-1.37, I²=88%), cardiovascular mortality (RR 0.87, 95% CI 0.67-1.13, I²=33%), MI (RR 0.86, 95% CI 0.65-1.13, I²=52%), ischemic stroke (RR 0.82, 95% CI 0.64-1.06, I²=0%), haemorrhagic stroke (RR 0.80, 95% CI 0.35-1.80, I²=49%), major bleeding (RR 0.96, 95% CI 0.74-1.23, I²=30%), repeat revascularization (RR 0.96, 95% CI 0.85-1.09, I²=0%), target vessel revascularization (RR 0.97, 95% CI 0.81-1.17, I²=0%), or stent thrombosis (RR 0.81, 95% CI 0.49-1.35, I²=0%). Funnel plot assessment showed significant publication bias in MACE, MI and stent thrombosis.
Conclusions
Clopidogrel monotherapy was associated with reduced MACE compared with aspirin among post-PCI patients, without increasing bleeding or ischemic complications. These findings support clopidogrel as an effective alternative antiplatelet monotherapy following PCI and warrant further randomized evaluation to inform guideline recommendations.Figure 1Figure 2