From the Guidelines
Andexanet alfa is recommended as the first-line treatment for the reversal of factor Xa inhibitors like apixaban (Eliquis) and rivaroxaban (Xarelto) in patients with life-threatening or uncontrolled bleeding. The dosing of andexanet alfa depends on the specific anticoagulant and when it was last taken, as outlined in the 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation 1. For patients who took their last dose of apixaban or rivaroxaban ≤8 hours ago or if the timing is unknown, a high dose is recommended: 800 mg IV bolus followed by a 960 mg IV infusion over 2 hours. For patients who took their last dose >8 hours ago, a low dose is used: 400 mg IV bolus followed by a 480 mg IV infusion over 2 hours. Andexanet alfa works by acting as a decoy protein that binds to factor Xa inhibitors with high affinity, preventing them from inhibiting native factor Xa and thus restoring normal hemostasis.
Some key points to consider when using andexanet alfa include:
- The onset of action is within 2 minutes, and the duration of action is approximately 2 hours 1
- Andexanet alfa may interfere with the anticoagulation effect of heparin, and coagulation parameters do not correlate with the drug's efficacy 1
- The ANNEXA-4 study demonstrated that andexanet alfa can rapidly and completely reverse the anticoagulant effect of rivaroxaban and apixaban, with effective hemostasis occurring in 79% of patients and thrombotic events occurring in 18% during the 30-day follow-up 1
- It's essential to monitor patients closely for thrombotic events and restart anticoagulation when medically appropriate after the bleeding is controlled.
Overall, andexanet alfa is a valuable option for reversing the anticoagulant effects of factor Xa inhibitors in patients with life-threatening or uncontrolled bleeding, and its use should be guided by the most recent clinical guidelines and evidence-based recommendations 1.
From the Research
Use of Andexanet Alfa as First Line Treatment for Reversal of Eliquis and Xarelto
- Andexanet alfa is approved as the first specific reversal agent for factor Xa (FXa) inhibitor-associated uncontrolled or life-threatening bleeding 2.
- Studies have shown that andexanet alfa is effective in reversing the anticoagulant effect of apixaban and rivaroxaban, with excellent or good hemostasis achieved in 82% of patients presenting with serious bleeding 3.
- A study comparing andexanet alfa to four-factor prothrombin complex concentrate (4F-PCC) for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhage found that andexanet alfa was associated with greater odds of achieving hemostatic effectiveness and decreased odds of mortality 2.
- Another study found that andexanet alfa may be used for urgent or emergent reversal of apixaban and rivaroxaban peri-procedurally with promising hemostatic outcomes 4.
Comparison to Other Reversal Agents
- A study comparing andexanet alfa to activated prothrombin complex concentrates (aPCCs) found that aPCCs could be an option in patients with major bleeding associated with apixaban or rivaroxaban, but may not be as effective as andexanet alfa 5.
- A study evaluating the operational processes and outcomes of patients with oral factor Xa inhibitor-associated intracranial hemorrhages treated with andexanet alfa or 4F-PCC found that andexanet alfa was associated with higher rates of good or excellent hemostasis and good functional outcome 6.
Key Findings
- Andexanet alfa is a effective and safe reversal agent for apixaban and rivaroxaban-associated bleeding 2, 4, 3.
- Andexanet alfa may be used as a first line treatment for reversal of Eliquis and Xarelto 2, 4, 3.
- Further prospective, comparative clinical research is warranted to fully evaluate the efficacy and safety of andexanet alfa 4.