Benefits and Harms of Oral Anticoagulation in Patients With Atrial Fibrillation and Prior Intracranial Hemorrhage

Study Questions:

What are the risks and benefits in atrial fibrillation (AF) patients with previous intracranial hemorrhage (ICH) treated with warfarin, compared to antiplatelet or no antithrombotic therapies?


This was a retrospective analysis of the National Health Insurance Research Database released by the Taiwan National Health Research Institutes. Among 307,640 AF patients with a CHA2DS2-VASc score ≥2, 12,917 patients with a history of ICH were identified. Propensity score-matched analyses were performed for two kinds of comparisons among patients with prior ICH: “antiplatelet agents versus no antithrombotic therapy” and “warfarin versus no antithrombotic therapy.” The clinical endpoint was occurrence of ischemic stroke; safety endpoint was occurrence of ICH.


Among patients with prior ICH, the rate of ICH and ischemic stroke in untreated patients was 4.2 and 5.8 per 100 person-years, respectively. A past history of ICH was an independent risk factor of further ICH with an adjusted hazard ratio of 5.27 (95% confidence interval [CI], 4.83-5.75; p < 0.01). Among patients with a CHA2DS2-VASc score ≥6, the number needed to treat (NNT) for preventing one ischemic stroke was lower than the number needed to harm (NNH) (37 vs. 56). Among patients with a CHA2DS2-VASc score <6, the NNT was higher than NNH (63 vs. 53). The use of antiplatelet agents was not associated with a lower risk of ischemic stroke, but did increase the risk of ICH, compared to patients without antithrombotic therapy, with an adjusted hazard ratio of 0.89 (95% CI, 0.78-1.01; p = 0.060) and 1.36 (95% CI, 1.19-1.57, p < 0.001), respectively.


The authors concluded that warfarin use may be beneficial for AF patients with prior ICH having a CHA2DS2-VASc score ≥6.


This is a very valuable study that provides guidance on anticoagulation/antiplatelet strategy in patients with AF following ICH. As the authors demonstrate and opine, ‘Given the high risk of recurrent ICH for patients with past history of ICH, the threshold for initiating warfarin for these patients may be different from the general AF population...our results suggest that warfarin may be considered for patients with a CHA2DS2-VASC ≥6 balancing the increased risk of ICH and benefits of stroke risk reduction.’ As the authors acknowledge, whether the use of novel oral anticoagulants could lower the threshold for stroke thromboprophylaxis in AF patients with prior ICH warrants further study.

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