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