Treatment strategies for patients with atrial fibrillation and anticoagulant-associated intracranial hemorrhage: an overview of the pharmacotherapy

ABSTRACT

Introduction

Oral anticoagulants (OAC) reduce stroke/systemic embolism and mortality risks in atrial fibrillation (AF). However, there is an inherent bleeding risk with OAC, where intracranial hemorrhage (ICH) is the most feared, disabling, and lethal complication of this therapy. Therefore, the optimal management of OAC-associated ICH is not well defined despite multiple suggested strategies.

Areas covered

In this review, the authors describe the severity and risk factors for OAC-associated ICH and the associated implications for using DOACs in AF patients. We also provide an overview of the management of OAC-associated ICH and treatment reversal strategies, including specific and nonspecific reversal agents as well as a comprehensive summary of the evidence about the resumption of DOAC and the optimal timing.

Expert opinion

In the setting of an ICH, supportive care/measures are needed, and reversal of anticoagulation with specific agents (including administration of vitamin K, prothrombin complex concentrates, idarucizumab and andexanet alfa) should be considered. Most patients will likely benefit from restarting anticoagulation after an ICH and permanently withdrawn of OAC is associated with worse clinical outcomes. Although the timing of OAC resumption is still under debate, reintroduction after 4–8 weeks of the bleeding event may be possible, after a multidisciplinary approach to decision-making.

KEYWORDS:

• Atrial fibrillation
• oral anticoagulants
• vitamin K antagonists
• direct oral anticoagulants
• intracranial hemorrhage
• intracranial bleeding

Article highlights

 

• Intracranial hemorrhage (ICH) is the most feared complication in atrial fibrillation (AF) patients taking oral anticoagulation and decision-making on resuming this therapy is challenging.

• In the setting of an ICH, the initial step should focus on classical actions for stopping the bleeding, including reduction of blood pressure, surgical hemostasis, fluid replacement, prohemostatic agents, blood transfusions, and other hemodynamic support.

• The second step is the reversal of anticoagulation: vitamin K, prothrombin complex concentrates (4F-PCCs), and fresh-frozen plasma for VKA users; and specific agents (idarucizumab and andexanet alfa) for dabigatran, rivaroxaban, and apixaban users.

• The decision of resuming oral anticoagulation needs to be individualized based on bleeding and stroke risks, characteristics of the ICH, potential factors related to bleeding, and the type of anticoagulant previously used.

• The optimal timing for restarting oral anticoagulation therapy is not clear but reintroduction at approximately 4-8 weeks after the bleeding event was effective and safe in most studies.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee received research support from AVID (who is a wholly owned subsidiary of Eli Lilly and Company), Pfizer Inc, and Boston Scientific. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.