What is the reversal strategy for Apixaban (Eliquis)?

From the Guidelines

Eliquis (apixaban) can be reversed in emergency situations using Andexxa (andexanet alfa), which is specifically designed to reverse Factor Xa inhibitors like Eliquis. The dosing of Andexxa depends on the dose of Eliquis and when it was last taken. For patients on standard Eliquis doses (5mg or 10mg), a high-dose regimen of Andexxa is typically used: 800mg IV bolus followed by a 960mg continuous infusion over 2 hours, as supported by the ANNEXA-4 study 1. In situations where Andexxa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg can be used as an alternative, though it's less specific and less effective, as noted in the 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants 1. Some key points to consider when using Andexxa include:

• Andexxa works by binding to the anticoagulant and preventing it from inhibiting Factor Xa, thus restoring normal blood clotting.
• The ANNEXA-4 study demonstrated that Andexxa decreased the median anti-FXa activity by 92% for both apixaban and rivaroxaban, with excellent or good hemostasis 12 hours after infusion 1.
• For less severe bleeding, supportive measures like local pressure, tranexamic acid, and temporarily holding Eliquis may be sufficient.
• After bleeding is controlled, a careful risk-benefit assessment should determine when to restart anticoagulation, typically after 24-72 hours depending on bleeding severity and the patient's thrombotic risk, as recommended by the 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants 1. It is also worth noting that Andexanet alfa has been studied in ongoing trials in patients on a DOAC with major bleeding and ICH, as mentioned in the 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants 1.

From the FDA Drug Label

The safety and efficacy of ANDEXXA were evaluated in two prospective, randomized, placebo-controlled studies, conducted in healthy volunteers (Study 1 ANNEXA-A; Study 2 ANNEXA-R) Both studies examined the percent change in anti-FXa activity, from baseline to nadir, for the low-dose and high-dose regimens of bolus followed by continuous infusion. The safety and efficacy of ANDEXXA were evaluated in an ongoing, prospective, single-arm, open-label study (Study 3 ANNEXA-4) in subjects presenting with acute major bleeding and who have recently received an FXa inhibitor

There is no information in the provided drug labels about the reversal of Eliquis. The studies mentioned are about the reversal of apixaban and rivaroxaban, but not Eliquis (which is another name for apixaban in some countries, but in the US, Eliquis is the brand name for apixaban). However, since apixaban is the same as Eliquis,

• Eliquis reversal can be achieved with andexanet alfa.
• The dose of andexanet alfa for Eliquis reversal is a 400 mg IV bolus followed by a 4 mg per minute continuous infusion for 120 minutes (total 480 mg) 2.
• The percent change from baseline in anti-FXa activity at its nadir was -92.3% for the andexanet alfa group compared to -32.7% for the placebo group 2.

From the Research

Eliquis Reversal Agents

Eliquis, also known as apixaban, is a factor Xa inhibitor used to prevent blood clots. In cases of intracranial hemorrhage, reversal agents may be necessary to quickly restore blood clotting. The following are some key points about Eliquis reversal:

• Andexanet alfa is a specific reversal agent for factor Xa inhibitors, including apixaban 3, 4, 5, 6.
• Four-factor prothrombin complex concentrates (4F-PCC) are also used as a reversal agent for apixaban, although they are not specific to factor Xa inhibitors 3, 4, 5, 7, 6.
• Studies have compared the effectiveness of andexanet alfa and 4F-PCC in reversing apixaban-associated intracranial hemorrhage, with some showing andexanet alfa to be more effective 3, 5, 6 and others showing similar effectiveness 4.

Comparison of Reversal Agents

Some key differences between andexanet alfa and 4F-PCC include:

• Hemostatic effectiveness: Andexanet alfa has been shown to have higher rates of hemostatic effectiveness in some studies 3, 5, 6.
• Thrombotic events: Andexanet alfa has been associated with lower rates of thrombotic events in some studies 5, while others have shown similar rates 4.
• Cost: Andexanet alfa is generally more expensive than 4F-PCC 6.
• Administration time: 4F-PCC may have a faster order-to-administration time than andexanet alfa 6.

Clinical Outcomes

Clinical outcomes for patients treated with andexanet alfa or 4F-PCC for apixaban-associated intracranial hemorrhage include:

• Mortality: Andexanet alfa has been associated with lower mortality rates in some studies 3, while others have shown similar rates 4.
• Functional outcome: Andexanet alfa has been associated with better functional outcomes in some studies 6.
• Thrombotic complications: Andexanet alfa has been associated with lower rates of thrombotic complications in some studies 5, while others have shown similar rates 4.