Intracranial Hemorrhage and Novel Anticoagulants for Atrial Fibrillation: What Have We Learned?

Intracranial hemorrhage (ICH) affects 0.2-0.5 % of atrial fibrillation (AF) patients taking a novel oral anticoagulant (NOAC) each year. About two thirds of ICHs are intracerebral and one quarter subdural. The 30-day case fatality of NOAC-associated ICH was similar to that of warfarin-associated ICH in two trials. Consistent predictors of ICH are increasing age, a history of prior stroke or TIA, and concomitant use of an antiplatelet drug. Compared to warfarin, the NOACs significantly reduce the risk of ICH by half (risk ratio = 0.44; 95 % CI: 0.37 to 0.51). Compared to aspirin, apixaban has a similar risk of ICH (risk ratio = 0.84; 95 % CI, 0.38 to 1.87). Current treatments for NOAC-associated ICH include nonactivated and activated prothrombin complex concentrate, which reverse the anticoagulant effects of the NOACs, but their effects on bleeding and patient outcome are not known. Future treatments for NOAC-associated ICH promise to include specific antidotes to dabigatran (e.g., aDabi-Fab, PER977) and factor Xa inhibitors (e.g., r-Antidote PRT064445, PER977).