Inter‐ and intra‐individual concentrations of direct oral anticoagulants: The KIDOAC study

• Published in: Journal of thrombosis and haemostasis 2022-01, Vol.20 (1), p.92-103
• Main Authors: Toorop, Myrthe M. A., Rein, Nienke, Nierman, Melchior C., Vermaas, Helga W., Huisman, Menno V., Meer, Felix J. M., Cannegieter, Suzanne C., Lijfering, Willem M.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Antagonists; Anticoagulants; blood coagulation test; Blood Coagulation Tests; Body mass index; Creatinine; Dabigatran; direct thrombin inhibitors; direct‐acting oral anticoagulant; Dosage; factor Xa inhibitor; HAEMOSTASIS; Humans; Male; Original; Pyridones; Regression analysis; Rivaroxaban; Thrombin; Thrombosis; Variability; Vitamin K
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.15563

Background Direct oral anticoagulants (DOACs) do not require concentration monitoring. However, whether DOAC concentrations are stable and their variation between and within patients is not well studied. Methods Patients on vitamin K antagonists (VKA) who switched to rivaroxaban, apixaban, or dabigatran were included between 2018 and 2020. Blood was drawn at DOAC trough and peak concentrations at week 0, 2, and 8. Plasma drug concentrations were determined by anti‐factor Xa concentrations (rivaroxaban, apixaban) or diluted thrombin time (dabigatran). Inter‐ and intra‐individual variability was assessed by calculating the coefficient of variation (CV). Linear regression models were employed to evaluate associations between DOAC trough concentrations and previous VKA dosage, creatinine clearance, and body mass index (BMI). Results One hundred fifty‐two patients were included, of whom 96 (63%) were male and with a mean age of 73.9 ± 8.4 years. For the inter‐individual variability, the CV ranged between 48% and 81% for trough values and between 25% and 69% for peak values among patients using the recommended DOAC dose. Intra‐individual variability was substantially lower, as here the CV ranged between 18% and 33% for trough values and between 15% and 29% for peak values among patients using the recommended DOAC dose. Previous VKA dosage and creatinine clearance were inversely associated with DOAC trough concentrations. No association was found between BMI and DOAC trough concentrations. Conclusion Inter‐individual variability of DOAC concentrations was higher than intra‐individual variability. Lower previous VKA dosage and creatinine clearance were associated with higher DOAC trough concentrations. These findings support further study into an optimal target range, in which the risks of both bleeding and thrombosis are minimal.