Direct, non-Vitamin K antagonist oral anticoagulants compared with warfarin for stroke with atrial fibrillation and cerebral small vessel disease

Background: Cerebral small vessel disease (CSVD) is not only associated with an increased risk of intracranial hemorrhage (ICH) in patients on oral anticoagulation, but also associated with an increased risk of ischemic stroke. Limited data support the benefits of direct, non-Vitamin K antagonist oral anticoagulants (direct oral anticoagulants [DOACs]) in acute ischemic stroke (AIS) or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (AF) and CSVD. We aimed to evaluate the effectiveness and safety of DOACs in AIS or TIA with AF and CSVD. Patients and Methods: We conducted a retrospective study with consecutive patients who experienced AIS or TIA with AF and CSVD from January 1, 2017 to December 31, 2019 in the Stroke Center at Beijing Luhe Hospital, Capital Medical University. Patients are followed for 12 months by outpatient visits or telephone interviews. The safety endpoint of this study was symptomatic ICH (sICH), while the efficacy endpoint was recurrent ischemic events (AIS or TIA). Patients in the DOACs group were compared with patients in the warfarin group using Chi-square tests or the continuity correction Chi-square tests. The safety and efficacy endpoint was progression-free survival assessed by the log-rank test. Results: A total of 542 patients were finally included in this study (353 in the DOACs group and 189 in the warfarin group). There were no significant differences in vascular risk factors, NIH Stroke Scale score at baseline, and CHA2DS2-VASc score between the two groups. There were no significant differences in recurrent events between the two groups (P = 0.68). Patients in the DOACs group showed lower risks of sICH (P = 0.03) and a shorter hospital stay (P = 0.03) compared to patients in the warfarin group followed over 12 months. Conclusion: DOACs were associated with lower risks of sICH and similar risks of the recurrent ischemic event as compared to the warfarin group with AF and CSVD. Patients in the DOACs group had shorter hospital stay when compared to patients in the warfarin group. DOACs may be a better option than warfarin for AIS or TIA patients with AF and CSVD for secondary prevention.