Abstract

Introduction: Renal dose adjustment is imperative to appropriate direct oral anticoagulant (DOAC) prescribing among patients with atrial fibrillation (AF). Serum creatinine is routinely used to estimate GFR (eGFRcr) in clinical practice, but eGFRcr may be less accurate in certain settings. It is unknown whether other kidney function biomarkers, like cystatin C, is helpful to guide DOAC dosing. Hypothesis: Appropriate DOAC dosing by eGFRcr but supratherapeutic dosing by cystatin C-based eGFR (eGFRcys) is associated with bleeding, compared to appropriate dosing by both eGFRcr and eGFRcys. Methods: We conducted observational study from the SCREAM project, a healthcare utilization cohort of Stockholm, Sweden, during 2006-2018. We identified patients with AF on DOACs who had creatinine and cystatin C measured on the same day. We calculated eGFRcr with the 2021 Chronic Kidney Disease (CKD)-EPI and eGFRcys with 2012 CKD-EPI cystatin C equations. We estimated defined daily dose consumed per day and considered <0.8 as a reduced dose. We separately classified supratherapeutic, subtherapeutic, and appropriate dosing by eGFRcr and eGFRcys, and examined the bleeding risk using Cox regression. Results: Among 5427 AF patients on DOACs, mean age (SD) was 76 (9) years and 43% were women. Compared to eGFRcr, eGFRcys identified more patients with CKD (61% for eGFRcys <60 ml/min/1.73 m 2 vs. 35% for eGFRcr <60 ml/min/1.73 m 2 ), as well as more patients with supratherapeutic dosing (7.9 vs. 2.4%). Among 3064 patients who were classified as appropriate dosing by eGFRcr, 312 (10.2%) were reclassified as supratherapeutic dosing by eGFRcys and had a higher risk of bleeding (hazard ratio=1.58, 95% CI: 1.03-2.42), compared with those who were classified as appropriate dosing by both eGFRcr and eGFRcys ( Table ). Conclusions: Appropriate DOAC dosing by eGFRcr but supratherapeutic dosing by eGFRcys was associated with a higher risk of bleeding. The findings suggest that eGFRcys may inform decisions on DOAC dosing.

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