Category: Professional Posters
Purpose: Andexanet alfa was developed as a specific reversal agent for the treatment of patients with major bleeding associated with the use of factor Xa (FXa) inhibitors. While thrombotic events (TEs) have been reported in patients receiving andexanet alfa, the scope, nature, and timing of these events have not been fully characterized. In this secondary analysis of the ANNEXA-4 study, the occurrence of TEs and restart of anticoagulation was investigated.
Methods: The ANNEXA-4 study was a prospective, single-arm, open-label clinical trial that evaluated the safety and efficacy of andexanet alfa in patients with acute major bleeding, including intracranial hemorrhage, gastrointestinal bleeding, and other critical site bleeding. Patients presenting with acute major bleeding within 18 hours after their last dose of FXa inhibitor were treated with a bolus plus infusion of andexanet alfa. The andexanet alfa dose was based on the identity, amount, and timing of the last FXa inhibitor dose. Safety outcomes, including the occurrence of TEs (investigator-reported and independently reviewed by an adjudication committee), were evaluated over 30 days after enrollment. The timing of restart of any anticoagulation (oral or parenteral) and specifically oral anticoagulation were recorded, in order to evaluate timing of TEs with respect to timing of anticoagulation restart.
Results: Among 352 patients treated with andexanet alfa, a total of 34 (9.7%) experienced one or more TEs within 30 days of enrollment. Strokes (4.0%) and deep vein thrombosis (3.7%) were the most frequent TE types, while myocardial infarctions (2.0%), pulmonary emboli (1.4%), and transient ischemic attacks (0.3%) were less common. Among patients with arterial TEs, 77.3% and 27.3% had been anticoagulated for atrial fibrillation and venous thromboembolism, respectively. The median time to first TE was 10.5 days. For various subgroups (e.g., age, sex, region of enrollment, medical history, baseline anti-FXa activity, FXa inhibitor dose, andexanet alfa dose), no factors were significantly associated with the occurrence of TEs. 220 (62%) patients received at least one dose of either parenteral or oral anticoagulant therapy during the 30 days after andexanet alfa treatment, with 145 (41%), 46 (13%), and 29 (8%) restarting at < 6 days, 6-14 days, and 15-30 days after the bolus, respectively. Of these patients, 8 (2%) had a TE after restarting any anticoagulation; the remainder occurred before anticoagulation was restarted. 100 (28%) of the 220 patients were restarted on oral anticoagulation during the 30-day follow-up. No TEs occurred after oral anticoagulation had been restarted.
Conclusion: In patients with acute, FXa inhibitor–associated major bleeding treated with andexanet alfa, TEs occurred in 9.7% of patients. Although TE rates were numerically greater in patients with intracranial bleeding than in those with gastrointestinal bleeding, no factors were significantly associated with the occurrence of TEs. No patient experienced a TE after restarting oral anticoagulation.