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Factor Xa Reversal in Intracranial Hemorrhage
Quick Takes
- Andexanet alfa is a specific reversal agent for factor Xa inhibitor anticoagulant medications.
- For patients with intracranial hemorrhage, use of andexanet alfa had a high degree of efficacy in reversing factor Xa activity and achieving hemostasis.
- Patients experiencing intracranial hemorrhage related to factor Xa inhibitor use experienced a high burden of complications, including 15% 30-day mortality.
Study Questions:
What is the hemostatic efficacy and reversal of anti-factor Xa (anti-FXa) activity with andexanet alfa in patients with intracranial hemorrhage (ICH) who were treated with FXa inhibitor anticoagulants?
Methods:
The authors performed a substudy of the ANNEXA-4 study, where patients with major bleeding ≤18 hours after taking an FXa inhibitor (apixaban or rivaroxaban) were treated with andexanet alfa. Brain imaging for patients with ICH was obtained at 1 and 12 hours following andexanet alfa treatment. Co-primary efficacy outcomes were the change in anti-FXa activity and hemostatic efficacy as 12 hours (excellent/good defined as ≤35% increase in hemorrhage volume/thickness). Safety outcomes included thrombotic events and death at 30 days.
Results:
A total of 227 patients with ICH were included in the safety population (51.5% male, mean age 79.3 years) and 171 patients in the efficacy population (99 spontaneous and 72 traumatic bleeds). In the efficacy evaluation, excellent/good hemostasis at 12 hours was achieved in 77/98 (78.6%) and 58/70 (82.9%) patients with spontaneous and traumatic ICH, respectively. The median percent change in anti-FXa activity from baseline to nadir was a 93.8% decrease for apixaban-treated patients (n = 99) and 92.6% for rivaroxaban-treated patients (n = 59). Death within 30 days occurred in 34/227 (15.0%) patients with ICH, while thrombotic events occurred in 21/227 (9.3%) patients.
Conclusions:
The authors concluded that andexanet alfa reduced anti-FXa activity with a high rate of hemostatic efficacy among patients with ICH following apixaban or rivaroxaban use.
Perspective:
While quite rare, ICH is the most feared complication for patients taking anticoagulant medications, including direct oral anticoagulants. The ANNEXA-4 study was a single-arm evaluation of andexanet alfa, a bolus plus infusion medication to reverse anti-Xa anticoagulant activity (apixaban and rivaroxaban). Given the high cost, many centers have chosen to restrict andexanet alfa use to patients with ICH and recent apixaban/rivaroxaban use. This substudy highlights that even with a high degree of efficacy (79-83% excellent/good hemostasis), these patients remain at high risk for complications (9.3% thrombotic events) and death (15% within 30 days) that may be related to underlying comorbidities in addition to their acute bleeding event. Large, prospective studies examining similar efficacy and safety outcomes for similar patients treated with prothrombin complex concentrate are lacking. For patients who present with ICH and recent use of apixaban or rivaroxaban, the ACC Expert Consensus Pathway recommends use of andexanet alfa, when available, for these patients with life-threatening bleeding events.
Clinical Topics: Anticoagulation Management, Dyslipidemia, Geriatric Cardiology, Noninvasive Imaging, Prevention, Lipid Metabolism, Novel Agents
Keywords: Anticoagulants, Blood Coagulation Factors, Diagnostic Imaging, Factor Xa, Factor Xa Inhibitors, Geriatrics, Hemorrhage, Hemostasis, Intracranial Hemorrhages, Neuroimaging, Prothrombin, Secondary Prevention, Thrombosis, Vascular Diseases
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