The use of andexanet alfa vs. 4-factor prothrombin complex concentrates in the setting of life-threatening intracranial hemorrhage

Objective Andexanet alfa is a targeted reversal agent for life threatening hemorrhage associated with direct acting oral anticoagulants (DOACs), but there is uncertainty regarding the benefit when compared to 4-factor prothrombin complex concentrate (4F-PCC) for this indication. We investigated the clinical outcomes and cost associated with reversal of DOACs in the setting of life-threatening intracranial hemorrhage (ICH). Methods A retrospective evaluation was conducted to evaluate patients with ICH in the setting of anticoagulation with DOAC from 9/1/2013 to 4/30/2020. Patients were included in the study if they received reversal with either andexanet alfa or 4F-PCC. Results Eighty-nine patients were included in the study. There was no statistically significant difference in 30-day mortality between patients who received andexanet alfa or 4F-PCC (52% vs. 35%, P = 0. 14). Radiographic stability of bleed was identified in 57% of patients receiving andexanet alfa vs. 58% of patients receiving 4F-PCC (P = 0. 93). Median length of stay was not different between the andexanet alfa and 4F-PCC populations (7 days IQR 6 – 12 vs. 6 days IQR 3–12, P = 0. 66). Median cost of reversal agent was higher in patients receiving andexanet alfa compared to 4F-PCC (15 000 IQR 15 000–27 000 vs. 11 650 IQR 8567–14 149). Conclusion Among patients with life-threatening intracranial hemorrhage in the setting of DOAC therapy, no clinical differences were observed with respect to selection of reversal agent. Prothrombin complex concentrates remain a viable alternative to reversal of DOAC therapy though multicenter, randomized, prospective studies are needed to further evaluate the role of 4F-PCC in the reversal of DOAC therapy.