Direct Oral Anticoagulant Concentrations in Obese and High Body Weight Patients: A Cohort Study
Anne Céline Martin1,2, William Thomas3, Zahra Mahir4
1Department of Cardiology, European Hospital Georges Pompidou, Paris, France.
Insights
Obese patients taking direct oral anticoagulants (DOACs) generally achieve therapeutic levels, despite concerns about high body weight affecting drug concentrations. Further studies are needed to confirm clinical outcomes with these anticoagulants in high body weight populations.
Area of Science:
- Pharmacology
- Clinical Medicine
- Obesity Research
Background:
- Direct oral anticoagulants (DOACs) are widely used for atrial fibrillation (AF) and venous thromboembolism (VTE).
- Obese individuals experience higher incidences of AF and VTE, yet trial data on DOACs in patients weighing over 120 kg are limited.
- This scarcity creates uncertainty regarding the efficacy and safety of DOACs in high body weight (BW) populations.
Purpose of the Study:
- To investigate the relationship between factor Xa (FXa) inhibitor concentrations, body weight (BW), and renal function in obese patients.
- To compare DOAC concentrations in high BW patients with those in unselected populations.
Main Methods:
- Prospective study of 100 patients weighing ≥ 120 kg receiving apixaban or rivaroxaban for AF or VTE.
- Measurement of peak or trough drug concentrations using specific chromogenic assays.
- Analysis of drug concentrations in relation to BW, BMI, and creatinine clearance.
Main Results:
- No linear correlation was found between FXa inhibitor concentrations and BW, BMI, or creatinine clearance.
- While some DOAC concentrations (apixaban troughs in AF, rivaroxaban peaks in VTE) were lower than in unselected groups, most fell within the therapeutic range.
- Only two trough concentrations were below the expected range, with 109 out of 116 measurements within the on-therapy range.
Conclusions:
- Obese patients typically achieve therapeutic concentrations of FXa inhibitors.
- Current findings suggest DOACs are generally effective in high BW individuals.
- Further research is warranted to evaluate the clinical outcomes associated with DOAC use in this specific patient group.
Background:
Direct oral anticoagulants (DOACs) are prescribed for atrial fibrillation (AF) and venous thromboembolism (VTE) and both occur more frequently in obese patients. Outcomes from DOAC trials included few individuals ≥ 120 kg leading to uncertainty whether high body weight (BW) reduces DOAC concentrations.
Objectives:
This article investigates the relationship between factor Xa (FXa) inhibitor concentrations, BW, and renal function, and compares them in high BW patients with unselected populations.
Methods:
Consecutive patients in two United Kingdom centers, weighing ≥ 120 kg receiving 5 mg twice daily apixaban or 20 mg once daily rivaroxaban for AF or VTE were prospectively included. Peak or trough concentrations were measured using specific chromogenic assays, expressed in mean or median (5th-95th percentiles). On-therapy range was the interval from the 5th percentile trough concentration to the 95th percentile peak concentration.
Results:
One hundred patients were included; age range: 23 to 78 years, 31% were women, 58% had AF, creatinine clearance range: 67 to 474 mL/min. Median BW was 139 kg, and 84% had body mass index (BMI) ≥ 40 kg/m2. DOAC peak and trough concentrations varied from 44 to 727 and 14 to 299 ng/mL, respectively. There was no linear relationship between FXa inhibitor concentrations at peak or trough and BW or BMI, and creatinine clearance. Apixaban troughs in AF and rivaroxaban peaks in VTE were lower than in unselected populations. However, only two trough concentrations were below the expected range, and 109/116 were within the on-therapy range.
Conclusion:
These data indicated that obese or high BW patients generally achieve therapeutic FXa inhibitor concentrations. However, further investigations assessing clinical outcomes are required.
Related Concept Videos
01:21Drug Dosing: Obese Patients
01:25Pharmacokinetics in Obese Patients: Drug Absorption and Distribution
01:20Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:29Venous Thrombosis III: Interprofessional Care