The increasing incidence of ischemic stroke in patients receiving direct oral anticoagulants (DOACs) highlights the heightened risk of subsequent ischemic events.1 Yet, the effectiveness and safety of antithrombotic regimens following this condition remain uncertain.1 In this investigation, patient outcomes were compared between those receiving DOACs with or without an alternative antithrombotic regimen, and the risk factors for recurrent ischemic stroke while on anticoagulation were identified.1 The 6-year study period, spanning January 1, 2015 to December 31, 2020, included 45,946 non-valvular atrial fibrillation (NVAF) patients administered DOACs for stroke prevention.1 Among them, 2,908 patients experienced an ischemic stroke despite the DOAC treatment, and 2,337 NVAF patients were included in the final analysis.1 The findings demonstrated that switching to warfarin (aHR=1.96; 95% CI: 1.27-3.02; p=0.002) or another DOAC(aHR=1.62; 95% CI: 1.25-2.11; p<0.001) was associated with an elevated risk of recurrent ischemic stroke compared with maintaining the sameDOAC therapy.1 Furthermore, the addition of an antiplatelet agent did not exhibit a reduced risk of recurrent ischemic stroke.1 The risk factors of recurrent ischemic stroke include diabetes mellitus (DM), concurrent cytochrome P450/P-glycoprotein (CYP/P-gp) modulators, and large artery atherosclerotic disease (LAD).1