Disagreement in rivaroxaban dosing between Cockcroft–Gault and eGFR equations in nonvalvular atrial fibrillation: a statewide analysis

Rivaroxaban dosing for nonvalvular atrial fibrillation (NVAF) is based on Cockcroft–Gault creatinine clearance using actual body weight (CG-CrCl-ABW) per FDA labeling. Recent recommendations support utilizing the race-free CKD-EPI 2021 equation for estimating kidney function. However, it is unknown whether substituting estimated glomerular filtration rate (eGFR) for CG-CrCl-ABW would alter dosing recommendations. The purpose of this study was to evaluate differences in rivaroxaban dosing when renal function is estimated using CG-CrCl-ABW versus CKD-EPI 2021. This retrospective statewide cohort study included adults (≥ 18 years) with NVAF identified from the Michigan Anticoagulation Quality Improvement Initiative registry. The primary outcome was rivaroxaban dosing disagreements, defined as a difference in dose between CG-CrCl-ABW and CKD-EPI 2021 with body surface area (BSA) adjustment using the Du Bois formula. Agreement between methods was assessed using Cohen’s kappa. A total of 476 NVAF patients were included. The mean age was 69.7 years, weight was 95.6 kg and serum creatinine was 0.96 mg/dL. Dosing disagreement occurred in 4.8% of patients after adjustment using the CKD-EPI 2021 equation with substantial agreement (κ = 0.61, 95% CI 0.47–0.76) compared with CG-CrCl-ABW. The majority of these cases (87.0%) would have resulted in a higher rivaroxaban dose. Patients with dosing disagreement had higher CHA 2 DS 2 -VASc and HAS-BLED scores. In conclusion, use of eGFR by CKD-EPI 2021 resulted in dosing discordance compared with CG-CrCl-ABW. Patients with disagreement in dosing had higher predicted risks of stroke and bleeding. When disagreement exists, rivaroxaban dosing should follow CG-CrCl-ABW in accordance with FDA labeling until additional clinical outcome data becomes available.