What is the reversal strategy for Apixaban (apixaban)?

From the Guidelines

Apixaban reversal requires prompt administration of andexanet alfa (Andexxa), the specific reversal agent for factor Xa inhibitors like apixaban. For life-threatening bleeding, administer andexanet alfa as an IV bolus over 15-30 minutes, followed by a 2-hour infusion. The dosing depends on the timing of the last apixaban dose:

• for patients who took apixaban ≤8 hours ago or unknown timing, use the high dose (800 mg bolus, then 960 mg infusion) 1;
• for patients who took apixaban >8 hours ago, use the low dose (400 mg bolus, then 480 mg infusion) 1. If andexanet alfa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg can be used as an alternative 1. Additional supportive measures include activated charcoal if apixaban was ingested within 2-4 hours, discontinuation of apixaban, and local hemostatic measures. Laboratory monitoring should include complete blood count, coagulation studies, and renal function tests. Andexanet alfa works by acting as a decoy protein that binds to apixaban, preventing it from inhibiting factor Xa and thus restoring normal coagulation 1. After reversal, reassess the patient's need for anticoagulation and consider when to safely restart therapy, typically 24-72 hours after bleeding is controlled 1.

Some key points to consider:

• Andexanet alfa is a recombinant human FXa variant with the active-site serine residue replaced with alanine to eliminate catalytic activity and with the membrane-binding domain deleted to prevent incorporation into the prothrombinase complex 1.
• The ANNEXA-4 study demonstrated that andexanet alfa substantially reduced anti-factor Xa activity with clinically adjudicated effective hemostasis occurring in 79% of patients 1.
• Andexanet alfa may interfere with the anticoagulation effect of heparin, and its use should be carefully considered in patients receiving heparin therapy 1.
• The use of andexanet alfa is supported by recent guidelines, including the 2023 ACC/AHA/ACCp/HRS guideline for the diagnosis and management of atrial fibrillation 1 and the 2023 WSES guidelines on the management of trauma in elderly and frail patients 1.

Overall, andexanet alfa is a highly effective and safe reversal agent for apixaban, and its use should be considered in patients with life-threatening bleeding or those who require urgent surgery or invasive procedures 1.

From the FDA Drug Label

An agent to reverse the anti-factor Xa activity of apixaban is available The pharmacodynamic effect of apixaban tablets can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa may be considered, but have not been evaluated in clinical studies Andexanet alfa is an agent that can reverse the anti-factor Xa activity of apixaban.

The reversal strategy for Apixaban (apixaban) includes the use of Andexanet alfa, which is a specific reversal agent for apixaban. Additionally, Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa may be considered, but their effectiveness has not been evaluated in clinical studies 2.

From the Research

Reversal Strategy for Apixaban

The reversal strategy for apixaban, a direct-acting oral anticoagulant, involves the use of specific agents to counteract its anticoagulant effects in cases of bleeding or when urgent surgery is required.

• Andexanet alfa: This is a specific reversal agent for factor Xa inhibitors, including apixaban. Studies have shown that andexanet alfa can effectively reverse apixaban's anticoagulant effects 3, 4, 5.
• Four-factor prothrombin complex concentrate (4F-PCC): 4F-PCC has also been investigated for its potential to reverse apixaban's effects. Research indicates that 4F-PCC can rapidly reverse apixaban-mediated decreases in coagulation parameters 6, 5.
• Combination therapy: Some studies have explored the use of andexanet alfa in combination with 4F-PCC for the reversal of apixaban in patients with intracranial hemorrhage. The results suggest that this combination may be effective but also carries a risk of thrombotic complications 3, 5.

Clinical Outcomes

Clinical outcomes of patients receiving andexanet alfa or 4F-PCC for reversal of apixaban have been evaluated in several studies.

• Hemostatic efficacy: The studies have reported varying rates of hemostatic efficacy, ranging from approximately 55% to over 64% for patients receiving andexanet alfa or 4F-PCC 3, 5.
• Mortality and thrombotic events: Mortality rates and the incidence of thrombotic events have also been assessed, with some studies indicating a higher risk of thrombotic complications with 4F-PCC compared to andexanet alfa 3, 5.