학술논문
Kidney function estimators for drug dose adjustment of direct oral anticoagulants in older adults with atrial fibrillation
ORIGINAL ARTICLE
ORIGINAL ARTICLE
Document Type
Academic Journal
Author
Source
Clinical Kidney Journal. December 2023, Vol. 16 Issue 12, p2661, 11 p.
Subject
Language
English
ISSN
2048-8505
Abstract
INTRODUCTION Direct oral anticoagulants (DOACs) are recommended as firstline therapy in non-valvular atrial fibrillation (NVAF) [1]. Dose adjustment is necessary when kidney function is reduced. Guidelines of the US Food [...]
Background. The Cockcroft--Gault equation ([CrCl.sub.C-G]) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF). Methods. Participants of the Berlin Initiative Study with AF and treated with DOACs were included. We investigated [CrCl.sub.C-G] and estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration and European Kidney Function Consortium equations based on creatinine and/or cystatin C. Marginal structural Cox models yielded confounder-adjusted hazard ratios for the risk of mortality, thromboembolism and bleeding associated with dose status. Results. A total of 224 patients were included in the analysis (median age 87 years). Using [CrCl.sub.C-G], 154 (69%) had an appropriate dose of DOACs, 52 (23%) were underdosed and 18 (8%) were overdosed. During a 39-month median follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced thromboembolism and 60 (9.8/100 person-years) experienced bleeding. Dose status was not associated with mortality and thromboembolism, independent of the equation. Underdose status was associated with a lower risk of bleeding with all the equations compared with the appropriate dose group. In participants with discrepancies in dose status using [CrCl.sub.C-G] and eGFR equations, the occurrence of endpoints did not differ between participants having an appropriate dose using [CrCl.sub.C-G] or eGFR. Conclusion. In older adults with AF, the association of DOAC dose status with adverse events did not differ when using [CrCl.sub.C-G] or eGFR. Our results suggest that eGFR equations are not inferior to [CrCl.sub.C-G] within this context. Keywords: atrial fibrillation, creatinine clearance, glomerular filtration rate, older adults, oral anticoagulant drug
Background. The Cockcroft--Gault equation ([CrCl.sub.C-G]) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF). Methods. Participants of the Berlin Initiative Study with AF and treated with DOACs were included. We investigated [CrCl.sub.C-G] and estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration and European Kidney Function Consortium equations based on creatinine and/or cystatin C. Marginal structural Cox models yielded confounder-adjusted hazard ratios for the risk of mortality, thromboembolism and bleeding associated with dose status. Results. A total of 224 patients were included in the analysis (median age 87 years). Using [CrCl.sub.C-G], 154 (69%) had an appropriate dose of DOACs, 52 (23%) were underdosed and 18 (8%) were overdosed. During a 39-month median follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced thromboembolism and 60 (9.8/100 person-years) experienced bleeding. Dose status was not associated with mortality and thromboembolism, independent of the equation. Underdose status was associated with a lower risk of bleeding with all the equations compared with the appropriate dose group. In participants with discrepancies in dose status using [CrCl.sub.C-G] and eGFR equations, the occurrence of endpoints did not differ between participants having an appropriate dose using [CrCl.sub.C-G] or eGFR. Conclusion. In older adults with AF, the association of DOAC dose status with adverse events did not differ when using [CrCl.sub.C-G] or eGFR. Our results suggest that eGFR equations are not inferior to [CrCl.sub.C-G] within this context. Keywords: atrial fibrillation, creatinine clearance, glomerular filtration rate, older adults, oral anticoagulant drug