A UK-wide analysis of 2265 patients receiving a reversal agent for direct oral anticoagulant-associated bleeding

Abstract

Background: Reversal agents are used in patients taking direct oral anticoagulants (DOACs) to manage bleeding, but evidence for their effectiveness remains limited.

Objectives: Assess the proportion of patients treated with a reversal agent for DOAC-associated bleeding who had major bleeding, and to evaluate their outcomes.

Methods: This was a retrospective, observational audit across 65 hospitals in the United Kingdom. Adults who received andexanet alfa, idarucizumab, or four factor prothrombin complex concentrate (4F-PCC) for DOAC-associated bleeding between October 2020 and June 2023 were included. Data were collected on demographics, medical history, bleed site and severity, reversal agent, thrombosis, and 90-day mortality. A propensity score-matched analysis was performed to estimate the cumulative incidence of thrombosis and death according to reversal agent in gastrointestinal hemorrhage.

Results: Of 2,265 patients, 875 (38.6%) had gastrointestinal bleeding and 1,012 (44.7%) had intracranial hemorrhage. Median age was 81 years. Median time from bleed onset to reversal was 6.5 hours and 16.0 hours from last anticoagulant dose. Of 1,253 patients with non-intracranial bleeds, 1,001 (79.9%) had major hemorrhage. In a propensity score-matched analysis of 494 patients with gastrointestinal bleeding, there was no significant difference in 90-day-mortality with andexanet alfa compared to 4F-PCC (36.4% vs 32.4%) but andexanet alfa was associated with a significantly increased 30-day incidence of stroke (4.5% vs 0%).

Conclusions: Reversal agents were generally used in patients with clinical evidence of major bleeding but were administered long after the last anticoagulant dose. In gastrointestinal bleeding, andexanet alfa was associated with a higher thrombotic risk than PCC.

Keywords: Anticoagulation; andexanet alfa; antidotes; apixaban; dabigatran; drug-related side effects and adverse reactions; edoxaban; factor Xa inhibitors; gastrointestinal hemorrhage; intracerebral hemorrhage; intracranial hemorrhage; prothrombin complex concentrate; rivaroxaban; thrombin inhibitors.