What is the mechanism of action (MOA) of apixaban (Eliquis)?

From the Guidelines

Apixaban (Eliquis) is a direct oral anticoagulant (DOAC) that works by selectively inhibiting factor Xa in the coagulation cascade, preventing the conversion of prothrombin to thrombin and thereby reducing thrombin-mediated activation of platelets and the conversion of fibrinogen to fibrin. This mechanism of action is supported by the 2016 ESC guidelines for the management of atrial fibrillation, which compared the characteristics of approved non-vitamin K antagonist oral anticoagulants, including apixaban, dabigatran, rivaroxaban, and edoxaban 1. The guidelines highlight that apixaban is an oral direct factor Xa inhibitor, which is consistent with its mechanism of action. Additionally, the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation provides further evidence for the mechanism of action of apixaban, stating that it is a direct factor Xa inhibitor 1. Some key points about apixaban include:

• It is typically dosed at 5 mg twice daily for most indications
• A reduced dose of 2.5 mg twice daily is recommended for patients meeting certain criteria, such as advanced age (≥80 years), low body weight (≤60 kg), or elevated serum creatinine (≥1.5 mg/dL)
• The medication reaches peak plasma concentration within 3-4 hours of administration and has a half-life of approximately 12 hours, requiring twice-daily dosing for consistent anticoagulation effect
• Apixaban has been shown to be effective in preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation, with a lower risk of major bleeding compared to warfarin 1. Overall, the evidence supports the use of apixaban as a direct oral anticoagulant that works by selectively inhibiting factor Xa in the coagulation cascade.

From the FDA Drug Label

Apixaban is a selective inhibitor of FXa. It does not require antithrombin III for antithrombotic activity. Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. Apixaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, apixaban decreases thrombin generation and thrombus development.

The mechanism of action (MOA) of apixaban (Eliquis) is as a selective inhibitor of factor Xa (FXa). It works by:

• Inhibiting free and clot-bound FXa
• Inhibiting prothrombinase activity
• Indirectly inhibiting platelet aggregation induced by thrombin
• Decreasing thrombin generation and thrombus development 2

From the Research

Mechanism of Action (MOA) of Apixaban

• Apixaban is a potent, direct, selective, and orally active inhibitor of coagulation factor Xa 3
• It inhibits both free factor Xa and prothrombinase activity, and clot-bound factor Xa activity 4
• The inhibition mechanism of apixaban is characterized by a K(i) of 0.25 nM at 37°C, an association rate constant of approximately 20 μM(-1) s(-1), and a dissociation half-life of 1-2 min 3
• Under physiological conditions, apixaban exhibits mixed-type inhibition and maintains high factor Xa affinity with a K(i) of 0.62 nM and association rate constant of 12 μM(-1) s(-1) for prothrombinase, and a K(i) of 1.7 nM and association rate constant of 4 μM(-1) s(-1) for the prothrombinase:prothrombin complex 3

Pharmacokinetics and Pharmacodynamics

• Apixaban has a plasma elimination half-life of 12 hours and is administered in a twice-daily dosing regimen without the need for anticoagulation monitoring or dosage adjustment 5, 6
• The pharmacokinetics of apixaban are consistent across a broad range of patients, with limited clinically relevant interactions with most commonly prescribed medications 7
• The pharmacodynamic effect of apixaban is closely correlated with apixaban plasma concentration 7

Clinical Applications

• Apixaban is approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non-valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep vein thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism 7
• Apixaban has been shown to be effective in preventing stroke and systemic embolism in patients with atrial fibrillation, with a similar or improved safety profile compared to warfarin and aspirin 5, 4, 6