Direct oral anticoagulants versus warfarin for secondary prevention of cerebral infarction and bleeding in older adults with atrial fibrillation

Abstract Background Direct oral anticoagulants (DOACs) have been used for both primary and secondary prevention of cerebral infarction in older patients with atrial fibrillation (AF). However, whether DOACs are more effective and safer than warfarin for secondary prevention of cerebral infarction in older patients with AF remains unclear. Methods Using the Japanese Diagnosis Procedure Combination database, we identified patients with AF who were hospitalized for cerebral infarction from January 1, 2015 to March 31, 2019 and were aged ≥75 years at admission. We performed propensity score‐stabilized inverse probability of treatment weighting analyses to balance measured confounders between patients with AF receiving DOACs and those receiving warfarin after discharge. The primary outcomes were 365‐day readmission for (a) benefit: cerebral infarction or (b) harm: bleeding events after discharge. The secondary outcomes were 365‐day readmission for intracranial bleeding or gastrointestinal bleeding after discharge as well as all‐cause death during readmission. Using a Fine–Gray model, we compared the subdistribution hazard ratios (SHRs) of readmission between the DOAC group and warfarin group. Results We identified 101,389 eligible patients, including 80,726 patients receiving DOACs and 20,663 patients receiving warfarin. After the propensity score‐stabilized inverse probability of treatment weighting, the adjusted SHRs of readmission (95% confidence interval [CI]) for cerebral infarction, bleeding events, and intracranial bleeding in the DOAC group as compared with the warfarin group were 0.76 (0.71–0.81), 0.78 (0.68–0.90), and 0.69 (0.57–0.82), respectively. There was no significant difference in readmission for gastrointestinal bleeding (SHR, 1.01; 95% CI, 0.72–1.41) between the DOAC and warfarin groups. Conclusion In this retrospective nationwide study, DOACs were more effective and safer than warfarin for preventing reinfarction and bleeding events in patients with AF aged ≥75 years who have a history of cerebral infarction.