Table 1.

Pharmacologic properties of oral anticoagulants relevant to CKD

AnticoagulantMechanism of ActionT1/2 (h)MetabolismKidney Clearance (%)Dose eCrCl≥51 ml/minDose eCrCl<51–31 ml/minDose eCrCl<31 ml/min and DialysisApproved Reversal Agent
Warfarin (Coumadin)Vitamin K antagonist (factors II, VII, IX, and X)a25–60 (mean 40)bCYP450 2C9c0INR 2–3INR 2–3INR 2–3Yes: Vitamin K (oral or intravenous)
Dabigatran (Pradaxa)Factor II (thrombin) inhibitor12–14P-gp80150 mg twice daily150 mg twice dailyd75 mg twice daily (eCrCl 30–15 ml/min)Yes: Idarucizumab (intravenous)e
Apixaban (Eliquis)Factor Xa inhibitor12CYP450 3A4 P-gp255 mg twice daily2.5 mg twice daily if 2 of 3 criteriaf2.5 mg twice daily if 2 of 3 criteriafYes: Andexanet alfa (intravenous)
Rivaroxaban (Xarelto)Factor Xa inhibitor7–11CYP450 3A4 -gp3520 mg once daily15 mg once daily15 mg once daily (eCrCl 30–15 ml/min)Yes: Andexanet alfa (intravenous)
Edoxaban (Savaysa)Factor Xa inhibitor8–10CYP450 3A4 P-gp4060 mg once dailyg30 mg once dailyNoYes: Andexanet alfah (intravenous)
  • eCrCl, estimated creatinine clearance as measured by Cockcroft–Gault equation; CYP450 3A4, cytochrome P 450; INR, international normalized ratio; P-gp, glycoprotein.

  • a Warfarin diminishes the total quantity of clotting factors II, VII, IX, and X by 30%–50%.

  • b Warfarin t1/2 depends on the clearance time for each clotting factor (e.g., T1/2 of factor II=59 h and factor VII=6 h).

  • c Genetic variations in CYP450 influence the metabolism of warfarin (i.e., factor IX mutation in hereditary resistance to warfarin). Notable drug-drug interactions include selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, verapamil, diltiazem, and digoxin. There are additional food interactions with green leafy vegetables containing vitamin K.

  • d Some experts recommend 110 mg twice daily for patients with creatinine clearance (CrCl) <51 ml/min; however, this dose is not approved in the United States.

  • e Idarucizumab is an mAb approved as a 5 mg iv infusion without dose adjustment for kidney impairment for reversal of dabigatran in 2015.

  • f Dose determined according to ≥2 of the criteria: (1) age≥80 yr, (2) body wt ≤60 kg, or (3) serum creatinine (SCr)≥1.5 mg/dl.

  • g Not Food and Drug Administration approved with CrCl≥95 ml/min due to decreased efficacy to prevent arterial thromboembolism. However, post hoc analyses found that the net clinical benefit of edoxaban versus warfarin was consistent across kidney function.

  • h Andexanet is a factor Xa decoy protein designated as Breakthrough Therapy for reversal of apixaban, rivaroxaban, and edoxaban.