Clopidogrel versus aspirin monotherapy for secondary prevention after percutaneous coronary intervention - a nationwide population-based study

Abstract Background After percutaneous coronary intervention (PCI), patients are maintained on single antiplatelet therapy (SAPT) for secondary cardiovascular prevention after completing the guideline-recommended duration of DAPT for a period of time. We sought to compare the efficacy and safety of clopidogrel versus aspirin monotherapy for secondary prevention in patients who undergoing PCI in a population-based cohort study using the database from the National Health Insurance Service (NHIS) in Korea. Methods Of those who underwent PCI from 2009 to 2020, 133,343 patients were selected for analysis. (aspirin 65,802 patients, clopidogrel 67,653 patients). To balance between aspirin and clopidogrel users for the comparison of efficacy and safety, we applied the inverse probability of treatment weighting (IPTW) of propensity score method. The primary effectiveness outcome was major cardiovascular events (MACEs) as the composite of cardiovascular death, myocardial infarction (MI) or stroke. The primary safety outcome was any bleeding. We divided the short DAPT user (< 6 months of DAPT in patients with CCS or < 12 months of DAPT in patients with ACS) and long DAPT user (≥ 6 months of DAPT in patients with CCS or ≥ 12 months of DAPT in patients with ACS) by DAPT duration. Results After IPTW matching, overall the mean age of participants was 63.8±16.3 and the median SAPT duration was 3.3 (1.3 – 6.2). During period, the overall primary effectiveness outcome occurred in 4.1% in aspirin group and 2.8% in clopidogrel group (hazard ratio [HR], 0.684; 95% CI, 0.656 – 0.712; p-value <0.0001) (Figure 1-A). the overall primary safety outcome occurred in 2.4% in aspirin group and 2.1% in clopidogrel group (HR, 0.945; 95% CI, 0.899 – 0.994; p-value, 0.0287) (Figure 1-B). In short DAPT group, clopidogrel reduced the risk of MACE (HR, 0.761; 95% CI, 0.715 – 0.811; p-value, <0.0001) but did not reduce the risk of bleeding (HR, 0.973; 95% CI, 0.893 – 1.056; p-value, 0.5067) comaped with aspirin. However, in the long DAPT group, clopdiogrel reduced both MACE (HR, 0.633; 95% CI, 0.600 – 0.669; p-value <0.0001) and bleeding risk (HR, 0.931; 95% CI, 0.873 – 0.992; p-value, 0.028) compared with aspirin. (Figure 2) Conclusion Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after PCI reduced the risk of MACEs and bleeding. As shown in randomized controlled trials, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future clinical adverse events in real-world bid database.