Aspirin vs. Clopidogrel Monotherapy After 1 Month of ACS: Subgroup Analysis Based on Bleeding Risk and MI Type

Current guidelines still recommend dual antiplatelet therapy (DAPT) for 12 months following percutaneous coronary intervention (PCI) as the standard treatment in patients with acute coronary syndrome (ACS). As alternative strategies, monotherapy with aspirin or a P2Y12 inhibitor after short-term DAPT (1–6 months) are also considered to reduce the bleeding risk. However, the choice between aspirin or a P2Y12 inhibitor for monotherapy up to one year after PCI is based on treatment alternatives assessed in previous clinical trials, and to date, aspirin monotherapy has not been directly compared with clopidogrel after short-term DAPT in patients with ACS.

To define appropriate antiplatelet strategies, two key factors must be considered: high bleeding risk (HBR) and ACS type (ST-elevation myocardial infarction [STEMI] or non–ST-elevation myocardial infarction [NSTEMI]). The recently published one-year results of the STOPDAPT-3 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-3) showed that aspirin monotherapy, compared to clopidogrel, was associated with similar cardiovascular and bleeding risks between the first month and one year after PCI.

The aim of this subanalysis of multicenter, randomized STOPDAPT-3 study was to evaluate the effects of aspirin versus clopidogrel monotherapy in patients with ACS through subgroup analysis based on the presence or absence of HBR and the type of MI (STEMI or NSTEMI).

The primary endpoint (PEP) was a composite of cardiovascular death, myocardial infarction (MI), definite stent thrombosis, and ischemic stroke. Major bleeding was also assessed according to BARC types 3 or 5.

Researchers analyzed a total of 4353 patients, of whom 1711 had HBR (39.3%) (aspirin group: n = 847; clopidogrel group: n = 864), and 2457 had STEMI. There were no statistically significant differences between aspirin and clopidogrel for cardiovascular outcomes in subgroups with or without HBR (hazard ratio [HR]: 0.89 [95% confidence interval (CI): 0.61–1.30] and 1.08 [95% CI: 0.61–1.90]; p for interaction = 0.59) or in the STEMI and NSTEMI subgroups (HR: 1.01 [95% CI: 0.68–1.50] and 0.81 [95% CI: 0.48–1.37]; p for interaction = 0.51).

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Similarly, there were no significant differences in bleeding risk between subgroups based on hemorrhagic risk (HR: 0.73 [95% CI: 0.40–1.33] and 0.71 [95% CI: 0.23–2.24]; p for interaction = 0.97) or between the STEMI and NSTEMI subgroups (HR: 0.96 [95% CI: 0.46–2.01] and 0.53 [95% CI: 0.24–1.17]; p for interaction = 0.28).

Conclusion

In patients with ACS, aspirin monotherapy after one month of DAPT and clopidogrel monotherapy showed similar cardiovascular and bleeding outcomes from one month to one year after PCI, regardless of bleeding risk or ACS subtype (STEMI or NSTEMI).

Original Title: Aspirin vs Clopidogrel 1 Month After Acute Coronary Syndrome With High-Bleeding Risk or ST-Segment Elevation.

Reference: Yuki Obayashi, MD et al JACC Cardiovasc Interv. 2025.