Monitoring anti-factor Xa activity in patients with chronic thromboembolic pulmonary hypertension treated with factor...

Area of Science:

• Pharmacology
• Cardiology
• Hematology

Background:

• Direct oral anticoagulants (DOACs) are increasingly used for secondary prevention in chronic thromboembolic pulmonary hypertension (CTEPH).
• Limited data exist on the clinical effects and monitoring of DOACs, particularly factor Xa (FXa) inhibitors, in CTEPH patients.
• Understanding drug activity and its correlation with clinical outcomes is crucial for optimizing treatment.

Purpose of the Study:

• To evaluate the anti-factor Xa activity (AXA) in CTEPH patients treated with different FXa inhibitors (rivaroxaban, apixaban, edoxaban).
• To assess the relationship between AXA levels, drug dosage, and bleeding events.
• To determine the utility of heparin-calibrated AXA measurements in managing FXa inhibitor therapy in CTEPH.

Main Methods:

• Fifty consecutive CTEPH patients receiving rivaroxaban, apixaban, or edoxaban were enrolled.
• Heparin-calibrated AXA was measured at both peak and trough drug concentrations.
• Plasma drug concentrations and bleeding events were correlated with AXA levels.

Main Results:

• Median peak heparin-calibrated AXA was comparable across the three FXa inhibitors.
• Trough AXA was significantly higher with apixaban compared to rivaroxaban or edoxaban.
• Reduced-dosage edoxaban showed significantly lower peak AXA than reference dosages of all three drugs.
• Peak AXA correlated strongly with plasma concentrations of rivaroxaban and apixaban.
• Higher peak AXA (≥2.09 IU/mL) was associated with a significantly increased rate of bleeding.

Conclusions:

• Heparin-calibrated AXA monitoring may offer valuable insights for adjusting FXa inhibitor therapy in CTEPH patients.
• Trough AXA levels differ significantly among FXa inhibitors, with apixaban showing higher levels.
• Bleeding risk in CTEPH patients on FXa inhibitors is associated with higher peak AXA levels.