Aspirin-Free Strategy for PCI in Patients With High Bleeding Risk With or Without Acute Coronary Syndrome: A Subgroup Analysis From the STOPDAPT-3 Trial

BACKGROUND: The effects of the aspirin-free strategy on bleeding and cardiovascular events were unknown in patients with high bleeding risk (HBR), with or without acute coronary syndrome (ACS), undergoing percutaneous coronary intervention. METHODS: We conducted a subgroup analysis stratified by ACS among patients with HBR in the STOPDAPT-3 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-3), which randomly compared no-aspirin (prasugrel monotherapy) with dual antiplatelet therapy (DAPT) in patients with ACS and HBR. RESULTS: There were 3258 patients with HBR, including 1803 ACS and 1455 non-ACS patients. The effects of no-aspirin compared with DAPT at 1 month after percutaneous coronary intervention were not significant for major bleeding regardless of ACS or non-ACS (7.3% versus 7.9%; hazard ratio [HR], 0.91 [95% CI, 0.65–1.28], and 3.1% versus 2.9%; HR, 1.06 [95% CI, 0.58–1.93]; P interaction=0.66). There was a numerically higher risk in the no-aspirin group relative to the DAPT group for a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke in patients with ACS, but not in patients with non-ACS (7.9% versus 5.8%; HR, 1.39 [95% CI, 0.97–1.99], and 2.4% versus 3.0%; HR, 0.78 [95% CI, 0.41–1.47]; P interaction=0.12). There was a significant treatment-by-subgroup interaction for myocardial infarction (1.6% versus 0.3%; HR, 4.57 [95% CI, 1.31–15.89], and 1.4% versus 1.8%; HR, 0.78 [95% CI, 0.34–1.77]; P interaction=0.02). CONCLUSIONS: The aspirin-free strategy compared with the DAPT strategy failed to reduce major bleeding in patients with HBR irrespective of ACS. There was a signal of the excess risk of the aspirin-free strategy relative to the DAPT strategy for cardiovascular events, myocardial infarction in particular, in patients with ACS, but not in patients with non-ACS. The aspirin-free strategy may be considered as a potential treatment option after percutaneous coronary intervention in patients with non-ACS. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04609111.