Aspirin or Clopidogrel Following Dual Antiplatelet Therapy in PCI-Treated Acute Coronary Syndrome Patients: A Real-World Population-Based Study

Background: Recent guidelines on Chronic Coronary Syndromes, for long-term monotherapy after acute coronary syndrome (ACS) or revascularization, have upgraded the recommendation for clopidogrel to the same strength as aspirin. We aimed to evaluate temporal trends and predictors of aspirin use compared to clopidogrel monotherapy following dual antiplatelet therapy (DAPT) in light of recent evidence from RCTs. Methods: Between 2016 to 2024, using healthcare databases of Lombardy, we conducted a real-world study identifying patients aged ≥40 years with PCI-treated ACS treated with clopidogrel or aspirin following DAPT. After DAPT, the trend of prescribing patterns of clopidogrel or aspirin monotherapy was evaluated. Multivariable logistic regression analysis was performed to investigate the association between patients’ clinical profiles and the likelihood of receiving either treatment. Results: Among 28,088 patients, 4.6% (1279) received clopidogrel and 95.4% (26,809) aspirin as monotherapy. This prevalence remained substantially stable over time. Patients receiving clopidogrel were older (71.5 vs. 65.3), had a greater burden of comorbidities, and were more frequently exposed to concomitant medications for cardiovascular prevention (all p value < 0.001). Older age, history of vascular events, diabetes mellitus, and gastro-intestinal disorders were significantly predictive of the choice of clopidogrel monotherapy, while being male sex was associated with the probability of receiving aspirin. Conclusions: Despite emerging evidence favoring clopidogrel over aspirin, the latter continues to be widely used after DAPT. Paradoxically, clopidogrel is primarily preferred for older and more severely ill patients, suggesting that it may be likely perceived as an option in this subgroup population. Further studies are needed to evaluate changes in clinical approach in response to the latest evidence.