In a 2017 meta-analysis of phase III RCTs that assessed the efficacy and safety of non-VKA OACs vs warfarin in patients with atrial fibrillation and a history of stroke/TIA, 1.0% (89/8,657) of patients taking non-VKA OACs experienced an ICH, compared with 1.9% (165/8,642) of patients in the warfarin group.¹ The non-VKAs included in these studies were the direct OACs apixaban, dabigatran, edoxaban and rivaroxaban.^1,2

Abbreviations

ICH, intracranial haemorrhage; OAC, oral anticoagulant; RCT, randomized controlled trial; TIA, transient ischaemic attack; VKA, vitamin K antagonist.

References

1. Ntaios G, et al. Int J Stroke. 2017;12:589–96.
2. Heestermans M, et al. Cells. 2022;11:3214.

In a 2022 meta-analysis of adults with ICH receiving treatment with a DOAC, 22 studies that included 967 patients treated with 4F-PCC for DOAC reversal were assessed. Among those receiving 4F-PCC, the thromboembolic event rate was 8% and the all-cause mortality rate was 26%.¹ 

These data are supported by the results of the ANNEXA-I trial, in which patients who had taken factor Xa inhibitors within 15 hours prior to an acute ICH received either andexanet alfa or usual care. Of those in the efficacy population receiving usual care (n=228), 86% (n=195) received PCC within 3 hours of randomization. Thrombotic events occurred in 6% of patients and death in 26% in the usual care group (extended population, n=267).²

Abbreviations

4F-PCC, four-factor PCC; DOAC, direct oral anticoagulant; ICH, intracranial haemorrhage; PCC, prothrombin complex concentrate.

References

1. Chaudhary R, et al. JAMA Netw Open. 2022;5:e2240145.
2. Connolly SJ, et al. N Engl J Med. 2024;390:1745–55.

AHA/ASA 2022, APSC 2021, ACC 2020 and ESO 2019 guidelines all recommend that in patients with OAC-associated bleeding/OAC-ICH taking apixaban therapy, anticoagulation should be reversed with andexanet alfa, or with PCC if andexanet alfa is not available.^1–4

Abbreviations

ACC, American College of Cardiology; AHA, American Heart Association; APSC, Asian Pacific Society of Cardiology; ASA, American Stroke Association; ESO, European Stroke Association; ICH, intracranial haemorrhage; OAC, oral anticoagulant; PCC, prothrombin complex concentrate.

References

1. Greenberg SM, et al. Stroke. 2022;53:e282–361.
2. Chong DTT, et al. Eur Cardiol. 2021;16:e23.
3. Tomaselli GF, et al. J Am Coll Cardiol. 2020;76:594–622.
4. Christensen H, et al. Eur Stroke J. 2019;4:294–306.

AHA/ASA 2022 guidelines recommend that, in patients with nonvalvular atrial fibrillation and OAC-ICH, resuming anticoagulation to prevent thromboembolic events and reduce all-cause mortality should be based on weighing benefit and risk. Left atrial appendage closure may be considered to reduce the risk of thromboembolic events in such patients if they are deemed ineligible for anticoagulation.¹

Similarly, the ACC 2020 decision pathway recommends that the decision to restart anticoagulation in patients with OAC-associated bleeding should involve assessing the risk of a thromboembolic event (e.g. using the CHA₂DS₂-VASc score); considering the sequelae associated with thromboembolic events (e.g. higher mortality for ischaemic strokes with atrial fibrillation); as well as considering the net benefit of anticoagulation reinitiation in certain types of bleeds.²

Abbreviations

ACC, American College of Cardiology; AHA, American Heart Association; ASA, American Stroke Association; ICH, intracranial haemorrhage; OAC, oral anticoagulant.

References

1. Greenberg SM, et al. Stroke. 2022;53:e282–361.
2. Tomaselli GF, et al. J Am Coll Cardiol. 2020;76:594–622.