Anticoagulation-associated intracranial haemorrhage in the era of reversal agents
In patients taking oral anticoagulants (OACs), the annual rate of intracranial hemorrhage is 0.3% to 0.6%. Of these bleeds, 46% to 86% are intracerebral; 13% to 45% are subdural, and 1% to 8% are subarachnoidal. With 30- to 90-day mortality rates of 40% to 65%, intracerebral hemorrhage (ICH) has the worst prognosis.
When we published a review on OAC-associated ICH in 2006, vitamin K antagonists (VKAs), such as warfarin, were the only available OAC. Since then, the options have expanded to include 4 direct OACs (DOACs; Table I in the online-only Data Supplement): dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. For long-term use, the DOACs are licensed for stroke prevention in nonvalvular atrial fibrillation and for treatment of venous thromboembolism. Their approval was based on randomized controlled trials that compared them with warfarin for stroke prevention in >71 000 patients with nonvalvular AF and with VKAs in >27 000 patients with venous thromboembolism. These trials revealed that the DOACs were at least as effective as VKAs but were associated with less bleeding, particularly less ICH. With similar efficacy, better safety, and greater convenience compared with VKAs, most current guidelines recommend DOACs over VKAs for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism. It is not surprising, therefore, that prescriptions for DOACs have overtaken those for VKAs in some countries. Despite the rapid uptake of the DOACs, however, at least 40% of patients continue to receive VKAs.
Focusing on ICH in patients receiving OAC, this article (1) reviews the currently available evidence on reversal of DOACs and VKAs, (2) provides recommendations about reversal, and (3) identifies the remaining questions on ICH management.