Anticoagulation Reversal Agent Linked to Improved Survival in Patients With Intracranial Hemorrhage

Compared to 4-factor prothrombin complex concentrates (4F-PCC), andexanet alfa was linked to better hemostatic effectiveness and survival in patients with life-threatening bleeding, according to findings published in Critical Care.

“Andexanet alfa is a modified, recombinant, inactive form of human FXa developed to serve as a decoy to bind FXa inhibitor molecules and reduce anti-FXa activity...Factor concentrates, most notably [4F-PCC], have been used as alternative off-label strategies for the management of major bleeding despite an absence of prospective clinical trial data,” said Olivia S Costa, PharmD, BCPS, and coauthors.

Currently, no clinical trials exist comparing andexanet alfa to 4F-PCC. The research team sought to fill the gap by conducting a two-cohort, indirect comparative study of US patients experiencing apixaban- or rivaroxaban-associated intracranial hemorrhages.

For the andexanet alfa arm (n=107), researchers used data from the ANNEXA-4 study, in which patients were treated at hospitals between April 2015 and March 2020. The synthetic control arm (n=95) included patients treated in health systems from December 2016 to August 2020. 

Intracranial hemorrhages were confirmed radiographically, and patients were included only if they received their last dose of apixaban or rivaroxaban at least 24 hours before the bleeding event. Of note, patients were excluded if they had a surgery scheduled within 12 hours, a Glasgow Coma Scale score less than 7, or a hematoma volume greater than 60 mL.

The mean age was 79 years and Glasgow Coma Scale score was 14 across both cohorts. On average, reversal was initiated 2.3 hours after the initial scan, and a subsequent 12.2 hours passed between reversal and a repeat scan. Most patients (86%) had atrial fibrillation, and the bulk of intracranial hemorrhages were classified as single compartment (78%) or trauma-related (61%) and involved the intracerebral and/or intraventricular spaces (53%).

Compared to 4F-PCC, andexanet alfa was associated with higher odds of achieving hemostatic effectiveness (85.8% vs 68.1%; OR 2.73; 95% CI 1.16-6.42) and lower odds of mortality (7.9% vs 19.6%; OR 0.36; 95% CI 0.13-0.98) after 30 days. Researchers noted 2 thrombotic events in the cohort receiving andexanet alfa and 0 events with 4F-PCC.

“Our findings support current consensus guidelines published by international/national medical societies, which preferentially recommend the use of andexanet alfa over 4F-PCC for the management of apixaban- or rivaroxaban-associated life-threatening bleeds (including intracranial hemorrhage),” Dr Costa and coauthors concluded.

Reference:
Costa OS, Connolly SJ, Sharma M, et al. Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhage: a propensity score-overlap weighted analysis. Crit Care. 2022;26(1):180. doi:10.1186/s13054-022-04043-8