What is the mechanism of action of Rivaroxaban (Xarelto) and Apixaban?

From the Guidelines

Xarelto (rivaroxaban) and Apixaban (Eliquis) are direct oral anticoagulants (DOACs) that work by selectively inhibiting Factor Xa in the coagulation cascade, as evidenced by the most recent and highest quality study 1. The mechanism of action of these medications involves blocking Factor Xa, a critical enzyme that converts prothrombin to thrombin, which then converts fibrinogen to fibrin to form blood clots. By blocking Factor Xa, these medications prevent the formation of thrombin and subsequently inhibit clot formation. Unlike warfarin, which indirectly affects multiple clotting factors by inhibiting vitamin K, Xarelto and Apixaban directly target Factor Xa, providing more predictable anticoagulation effects. This mechanism allows for fixed dosing without routine coagulation monitoring. Both medications are rapidly absorbed, with Xarelto typically taken once daily (though dosing varies by indication) and Apixaban usually taken twice daily. These medications are used to prevent and treat various thromboembolic conditions including atrial fibrillation-related stroke, deep vein thrombosis, and pulmonary embolism. Some key points to consider when using these medications include:

• The dosing regimens, with Xarelto typically taken once daily and Apixaban usually taken twice daily 1
• The importance of monitoring for bleeding risks, as these medications can increase the risk of bleeding complications 1
• The availability of specific reversal agents, such as andexanet alfa, which may be needed in emergency situations 1
• The need to consider renal function when prescribing these medications, as they may be contraindicated or require dose adjustments in patients with severe renal impairment 1

From the FDA Drug Label

XARELTO is a selective inhibitor of FXa. It does not require a cofactor (such as Anti-thrombin III) for activity. Rivaroxaban inhibits free FXa and prothrombinase activity. Rivaroxaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, rivaroxaban decreases thrombin generation. 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 of both Xarelto (rivaroxaban) and apixaban is the inhibition of factor Xa (FXa), which plays a crucial role in the coagulation cascade.

• Key points about their mechanism of action include:
  • Inhibition of free and clot-bound FXa
  • Inhibition of prothrombinase activity
  • Indirect inhibition of platelet aggregation induced by thrombin
  • Decrease in thrombin generation and thrombus development Both Xarelto and apixaban do not require antithrombin III for their antithrombotic activity 2 3.

From the Research

Mechanism of Action of Xarelto and Apixaban

• Xarelto (rivaroxaban) is an oral direct factor Xa inhibitor, which means it works by inhibiting the activity of factor Xa in the coagulation cascade 4.
• Apixaban is also an oral factor Xa inhibitor, with a rapid onset of action and predictable pharmacokinetics, allowing for a fixed dose regimen 5, 6.
• The mechanism of action of both Xarelto and apixaban involves the inhibition of factor Xa, which is a critical component of the coagulation cascade, thereby preventing the formation of blood clots 4, 7.
• By inhibiting factor Xa, Xarelto and apixaban reduce the risk of venous thromboembolism (VTE) and pulmonary embolism (PE) 5, 4.

Key Characteristics of Xarelto and Apixaban

• Xarelto is administered at a fixed oral dose and does not require routine coagulation monitoring 4.
• Apixaban has a fixed-dose regimen, which simplifies treatment and eliminates the need for initial parenteral anticoagulant therapy and laboratory monitoring 5.
• Both Xarelto and apixaban have been shown to be effective and safe in the treatment and prevention of VTE and PE, with a lower risk of major bleeding compared to traditional anticoagulant therapies 5, 4.

Clinical Evidence

• Studies have demonstrated the efficacy and safety of Xarelto and apixaban in patients with acute deep-vein thrombosis (DVT) and PE 5, 4, 7.
• The EINSTEIN-DVT and EINSTEIN-PE trials showed that Xarelto was noninferior to standard therapy in the treatment of DVT and PE 4.
• Apixaban has been shown to decrease coagulation activity in patients with acute DVT, with similar efficacy and safety to low-molecular-weight heparin followed by vitamin K antagonist (LMWH/VKA) 7.