DOAC Renal Dosing Guide

Evidence Summary

RE-LY (Dabigatran)

Randomized 18,113 AF patients to dabigatran 110 mg BID, 150 mg BID, or warfarin. Dabigatran 150 mg BID was superior for stroke/SE prevention (RR 0.66); 110 mg BID was non-inferior with lower major bleeding. The 75 mg BID dose for CrCl 15-30 is based on pharmacokinetic modeling, not RCT data.

ROCKET-AF (Rivaroxaban)

Randomized 14,264 AF patients to rivaroxaban 20 mg daily vs. warfarin. Non-inferior for stroke/SE (HR 0.79 on-treatment). Patients with CrCl 30-49 received 15 mg daily. Must be taken with the evening meal for optimal absorption.

ARISTOTLE (Apixaban)

Randomized 18,201 AF patients to apixaban 5 mg BID vs. warfarin. Superior for stroke/SE (HR 0.79), major bleeding (HR 0.69), and all-cause mortality (HR 0.89). Dose reduction to 2.5 mg BID if ≥2 of: age ≥80, weight ≤60 kg, Cr ≥1.5 mg/dL. Notably, apixaban retains FDA labeling for ESRD/dialysis (5 mg BID standard).

ENGAGE AF-TIMI 48 (Edoxaban)

Randomized 21,105 AF patients to edoxaban 60 mg or 30 mg daily vs. warfarin. Both doses non-inferior for stroke/SE. Edoxaban 60 mg reduced major bleeding (HR 0.80). Contraindicated if CrCl >95 mL/min (reduced efficacy observed) or CrCl <15.

Common Dosing Errors

• Inappropriate dose reduction of apixaban in the absence of ≥2 qualifying criteria (age, weight, creatinine) -- leads to under-dosing and increased stroke risk.
• Using eGFR (CKD-EPI) instead of Cockcroft-Gault CrCl -- all DOAC trials used Cockcroft-Gault; eGFR may overestimate renal function in elderly patients.
• Prescribing edoxaban when CrCl >95 mL/min -- the ENGAGE AF trial showed reduced efficacy in this subgroup (FDA boxed warning).
• Forgetting rivaroxaban must be taken with food (evening meal) for adequate absorption of the 15 mg and 20 mg doses.
• Missing P-gp inhibitor interactions with dabigatran requiring dose adjustment.