Table 8

Dose Selection of Oral Anticoagulant Options for Patients With Nonvalvular AF and CKD (Based on Prescribing Information for the United States)

Renal FunctionWarfarin (238)Dabigatran(177)Rivaroxaban(178)Apixaban(179)
Normal/mild impairmentDose adjusted for INR 2.0–3.0150 mg BID (CrCl >30 mL/min)20 mg QD with the evening meal (CrCl >50 mL/min)5.0 or 2.5 mg BID
Moderate impairmentDose adjusted for INR 2.0–3.0150 mg BID (CrCl >30 mL/min)15 mg QD with the evening meal (CrCl 30–50 mL/min)5.0 or 2.5 mg BID
Severe impairmentDose adjusted for INR 2.0–3.0§75 mg BID (CrCl 15–30 mL/min)15 mg QD with the evening meal (CrCl 15–30 mL/min)No recommendation. See Section 4.2.2.2
End-stage CKD not on dialysisDose adjusted for INR 2.0–3.0§Not recommended (CrCl <15 mL/min)Not recommended (CrCl <15 mL/min)No recommendation. See Section 4.2.2.2
End-stage CKD on dialysisDose adjusted for INR 2.0–3.0§Not recommended (CrCl <15 mL/min)Not recommended (CrCl <15 mL/min)No recommendation. See Section 4.2.2.2#

AF indicates atrial fibrillation; BID, twice daily; CKD, chronic kidney disease; Cr, creatinine; CrCl, creatinine clearance; FDA, Food and Drug Administration; INR, international normalized ratio; and QD, once daily.

  • Renal function should be evaluated before initiation of direct thrombin or factor Xa inhibitors and should be reevaluated when clinically indicated and at least annually. CrCl should be measured using the Cockcroft-Gault method.

  • The concomitant use of P-glycoprotein inducers or inhibitors with dabigatran or the concomitant use of dual P-glycoprotein and strong CYP3A4 inducers or inhibitors with either rivaroxaban or apixaban, particularly in the setting of CKD, may require dosing adjustment or avoidance of concomitant drug use (see the FDA drug label at http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202155s002lbl.pdf, Section 8.6).

  • Use apixaban 2.5 mg BID if any 2 patient characteristics are present: Cr ≥1.5 mg/dL, ≥80 y of age, body weight ≤60 kg (179). Apixaban is not recommended in patients with severe hepatic impairment.

  • § Dose-adjusted warfarin has been used, but observational data on safety and efficacy are conflicting.

  • Modeling studies suggest that dabigatran 75 mg BID might be safe for patients with CrCl 15–30 mL/min, but this has not been validated in a prospective cohort. Some countries outside the United States use 110 mg BID (177).

  • No published studies support a dose for this level of renal function.

  • # In patients with end-stage CKD on stable hemodialysis, prescribing information indicates the use of apixaban 5 mg BID with dose reduction to 2.5 mg BID if the patient is ≥80 y of age or body weight is ≤60 kg.