Optimal antiplatelet therapy for acute coronary syndrome patients with high risk for both ischemia and bleeding

Abstract Objective: To investigate the impact of different regimens of dual antiplatelet therapy (DAPT) on the prognosis of acute coronary syndrome (ACS) patients with high risk of both ischemia and bleeding after percutaneous coronary intervention (PCI). Methods: A retrospective analysis was conducted on 1,816 ACS patients with high risk of ischemia and bleeding who underwent PCI at a single center from January 2017 to November 2022. Patients were divided into an intensive group (n=1046, ticagrelor 90 mg), a routine group (n=611, clopidogrel 75 mg), and a de-escalation group (n=159, ticagrelor 90 mg). All patients received DAPT, including aspirin, for a duration of ≥ 12 months after PCI. The primary endpoint was the net clinical adverse events (NACEs) that occurred during follow-up, including the composite endpoint of major adverse cardiovascular and cerebrovascular events (MACCEs) and major bleeding associated with the thrombolysis in myocardial infarction (TIMI) criteria. The secondary endpoint was MACCE, which included a composite endpoint of cardiogenic death, myocardial infarction, ischemia-driven revascularization, and stroke. The primary safety endpoint is defined as major or minor bleeding events according to the TIMI criteria. Results: Compared with the de-escalation group, the intensive group had a lower incidence of NACEs (6.5% vs. 12.6%, P=0.011) and MACCEs during follow-up (4.4% vs. 11.9%, PP=0.003), especially for minor bleeding events (19.5% vs. 14.4%, P=0.007). Cox regression analysis revealed no statistically significant difference in the incidence of NACEs among the three DAPT regimens. Compared with the de-escalation group, both the intensive and routine groups had a reduced incidence of MACCEs (HR=0.334, HR=0.508, respectively); however, compared with the routine group, the intensive group had an increased incidence of bleeding events (HR=1.426), especially minor bleeding events (HR=1.395). Conclusion: For ACS patients with a high risk for both ischemia and bleeding, Aspirin combined with clopidogrel is recommended, as it not only reduces the incidence of ischemic events but also does not increase bleeding events. Choosing aspirin combined with ticagrelor to enhance antiplatelet therapy may reduce the risk of ischemic events, but minor bleeding events is increased. For this type of patient, de-escalation treatment is not recommended.