Does an elevated International Normalized Ratio (INR) need to be reversed in a patient on Eliquis (apixaban)?

From the Guidelines

No, an elevated INR does not need to be reversed in a patient taking Eliquis (apixaban). Eliquis is a direct oral anticoagulant (DOAC) that works by directly inhibiting factor Xa in the coagulation cascade, and its anticoagulant effect is not measured by the INR test. INR is specifically designed to monitor vitamin K antagonists like warfarin, not DOACs like Eliquis. If a patient on Eliquis has an elevated INR, this is likely coincidental or due to other factors such as liver disease or vitamin K deficiency, rather than a direct effect of the medication.

Key Points to Consider

• The INR test is not applicable for monitoring the anticoagulant effect of Eliquis (apixaban) as it is specifically designed for vitamin K antagonists like warfarin 1.
• For patients on Eliquis who are experiencing bleeding or require urgent surgery, specific reversal agents like andexanet alfa (Andexxa) may be used rather than treatments aimed at correcting the INR 1.
• Other coagulation tests such as anti-factor Xa assays would be more appropriate to assess the drug's activity, though these are not routinely performed in clinical practice 1.
• The management of anticoagulant-associated bleeding, including the use of reversal agents, should be guided by clinical judgment and the specific circumstances of the patient, including the type and timing of anticoagulant dosing 1.

From the FDA Drug Label

Apixaban tablets should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding [see Warnings and Precautions (5. 2)] Switching from warfarin to apixaban: Warfarin should be discontinued and apixaban started when the international normalized ratio (INR) is below 2. 0.

The FDA drug label does not provide direct guidance on reversing an elevated INR in a patient on Eliquis (apixaban). However, it does provide guidance on switching from warfarin to apixaban, which suggests that an INR below 2.0 is desired before starting apixaban. Reversal of elevated INR is not directly addressed in the context of a patient already on apixaban. Therefore, no conclusion can be drawn regarding the need to reverse an elevated INR in this scenario 2.

From the Research

Reversal of Elevated INR in Patients on Apixaban

• The management of elevated International Normalized Ratio (INR) in patients on apixaban is not as straightforward as in patients on warfarin, as apixaban is a non-vitamin K antagonist (NOAC) 3.
• Studies have shown that apixaban can prolong INR, but the clinical significance of this elevation is not well understood 4, 5.
• In patients with end-stage renal disease on hemodialysis, apixaban has been associated with extreme elevation in INR, but this is a rare event 4.
• The use of andexanet alfa, a reversal agent for apixaban, is approved for patients with life-threatening bleeding, but its use in patients with elevated INR without bleeding is not indicated 4.
• There is limited evidence on the management of elevated INR in patients on apixaban, and further studies are needed to determine the clinical significance of INR elevation and to establish guidelines for management 4, 5.

Comparison with Warfarin

• In patients on warfarin, elevated INR is a well-established risk factor for bleeding, and reversal of anticoagulation is often necessary 6, 7.
• The management of elevated INR in patients on warfarin typically involves withdrawal of the drug, administration of vitamin K, or use of prothrombin complex or fresh frozen plasma 6.
• In contrast, the management of elevated INR in patients on apixaban is not as well established, and further research is needed to determine the best approach 3, 4, 5.

Clinical Implications

• Clinicians should be aware of the potential for apixaban to elevate INR, and should monitor patients for signs of bleeding or other adverse effects 4, 5.
• The use of INR to monitor anticoagulant activity in patients on apixaban is not recommended, as it is not a reliable marker of anticoagulation 4, 5.
• Further research is needed to determine the clinical significance of INR elevation in patients on apixaban, and to establish guidelines for management 4, 5.