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Inter- and intra-individual concentrations of direct oral anticoagulants: The KIDOAC study.
Toorop, Myrthe M A; van Rein, Nienke; Nierman, Melchior C; Vermaas, Helga W; Huisman, Menno V; van der Meer, Felix J M; Cannegieter, Suzanne C; Lijfering, Willem M.
Afiliación
  • Toorop MMA; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
  • van Rein N; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
  • Nierman MC; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands.
  • Vermaas HW; Thrombosis Service of Amsterdam (Atalmedial), Amsterdam, the Netherlands.
  • Huisman MV; Thrombosis Service of the Hague (LabWest), The Hague, the Netherlands.
  • van der Meer FJM; Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
  • Cannegieter SC; Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
  • Lijfering WM; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
J Thromb Haemost ; 20(1): 92-103, 2022 01.
Article en En | MEDLINE | ID: mdl-34664401
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dabigatrán / Anticoagulantes Tipo de estudio: Prognostic_studies Límite: Aged / Aged80 / Humans / Male Idioma: En Revista: J Thromb Haemost Asunto de la revista: HEMATOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dabigatrán / Anticoagulantes Tipo de estudio: Prognostic_studies Límite: Aged / Aged80 / Humans / Male Idioma: En Revista: J Thromb Haemost Asunto de la revista: HEMATOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido