How does Eliquis (apixaban) affect the International Normalized Ratio (INR)?

From the Guidelines

Eliquis (apixaban) does not reliably affect the International Normalized Ratio (INR) and should not be monitored using INR testing. Unlike warfarin, which is specifically monitored using INR, Eliquis works through a different mechanism by directly inhibiting Factor Xa in the coagulation cascade. When patients take Eliquis, their INR values may show small, inconsistent, and clinically insignificant elevations that do not correlate with the drug's anticoagulant effect, as suggested by the lack of specific coagulation tests for dose adjustment in the 2012 ESC guidelines for the management of atrial fibrillation 1.

Key Points to Consider

• Eliquis is prescribed at fixed doses without the need for routine coagulation monitoring, as stated in the guidelines for the management of atrial fibrillation 1.
• The guidelines emphasize that NOACs, including Eliquis, do not require dose adjustment based on specific coagulation tests, such as INR for VKAs 1.
• For patients taking Eliquis, INR testing may yield misleading results and should not guide management decisions, highlighting the importance of understanding the distinct mechanisms of action of different anticoagulants.
• Healthcare providers should be aware of the differences in monitoring and management between Eliquis and other anticoagulants like warfarin, to ensure appropriate patient care and minimize potential risks.

Clinical Implications

• The lack of a reliable effect of Eliquis on INR values means that healthcare providers should not attempt to adjust Eliquis dosing based on INR results, as this could lead to inappropriate and potentially dangerous decisions.
• Instead, Eliquis should be managed according to its prescribed fixed doses and clinical guidelines, taking into account patient-specific factors such as renal function and bleeding risk, as outlined in the 2012 ESC guidelines 1.

From the FDA Drug Label

As a result of FXa inhibition, apixaban prolongs clotting tests such as prothrombin time (PT), INR, and activated partial thromboplastin time (aPTT). Changes observed in these clotting tests at the expected therapeutic dose, however, are small, subject to a high degree of variability, and not useful in monitoring the anticoagulation effect of apixaban. Apixaban affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin

Eliquis (apixaban) affects the International Normalized Ratio (INR), but the changes are small and subject to a high degree of variability, making INR not useful in monitoring the anticoagulation effect of apixaban. Additionally, when switching from apixaban to warfarin, apixaban's effect on INR should be considered, as initial INR measurements may not be reliable for determining the appropriate warfarin dose 2.

From the Research

Effects of Eliquis on INR

• Eliquis (apixaban) has been associated with prolongation of the prothrombin time and the international normalized ratio (INR) 3, 4, 5.
• Studies have shown that apixaban can cause a notable increase in INR in hospitalized patients, with a median INR of 1.4-1.7 reported in some cases 3, 4.
• The clinical significance of this increase is not clear, but it is important for clinicians to understand the association between apixaban and INR to avoid inappropriate interpretation of routine coagulation assays 3.
• In patients with end-stage renal disease on hemodialysis, apixaban has been reported to cause extreme elevation in INR, with a case report describing an INR of 27.42 4.
• The INR elevation caused by apixaban is thought to be due to the drug's effect on the prothrombin time, and plasma concentration of apixaban has been found to correlate with INR 4.

Comparison with Other Anticoagulants

• Rivaroxaban, another direct factor Xa inhibitor, has also been shown to elevate INR, with a significantly higher elevation compared to apixaban 5.
• The INR elevation caused by these drugs is not a reliable marker of their anticoagulant activity, and monitoring of INR is not recommended for patients on apixaban or rivaroxaban 3, 5.

Clinical Utility of INR

• The INR is a widely used measure of blood coagulation, and its clinical utility has been established in the monitoring of oral anticoagulant therapy 6, 7.
• The INR has been shown to be a safer way to monitor oral anticoagulation, with a better correlation with hemorrhage and thrombosis compared to the prothrombin time ratio 7.