Dabigatran was the first FDA-approved NOAC and is a potent, direct inhibitor of thrombin (Faktor IIa). Its serum half-life is 12-17 hours and is 80% renaly excreted (Table 1) (5, 6). The FDA recommended dose of dabigatran in patients with CrCL > 30 mL/min is 150 mg twice daily. However, the ESC guidelines recommend in patients with CrCl 30-49 mL/min to use the 110 mg BID dose. A subgroup analysis of the RE-LY trial (7) which included patients with CrCl 30-49 mL/min demonstrated a lower risk of stroke/systemic embolism and a similar risk of major bleeding with dabigatran in comparison to warfarin (8). Based on a pharmacokinetic modeling, FDA but not EMA approved a lower dose of dabigatran 75 mg BID in patients with CrCl 15-30 ml/mL (9, 10).
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Rivaroxaban has a half-life between 5 to 9 hours and renal clearance of 36%. Apixaban is 25% excreted through kidneys and its half-time is 12 hours. Finally, edoxaban the most recent Factor-Xa inhibitor exhibits a renal elimination of 50% and has a serum half-life of approximately 12 hours. Rivaroxaban (20 mg OD), edoxaban (60 mg OD) and apixaban (5mg BID) are recommended without any dose adjustment in patients with a CrCl > 50 mL/min. FDA has approved rivaroxaban 15 mg daily and edoxaban 30 mg daily in patients with CrCl 15-49 mL/min. A reduced dose of apixaban is recommended if two of three criteria are present: serum creatinine ≥ 1.5 mg/dl, age ≥ 80 years, body weight ≤ 60kg. The recommendation regarding a reduced dose of rivaroxaban (15mg) in CKD was based on a second analysis of the ROCKET-AF (15). Among patients with mild or moderate renal impairment rivaroxaban preserved the benefit of warfarin in preventing stroke and systemic embolism, while bleeding events were similar but fatal bleeding occurring less often with rivaroxaban (16). In respect to apixaban, a second analysis of the ARISTOTELE study (17), which included 3017 patients with CrCl of 25-50 mL/min showed a same efficacy of apixaban compared to warfarin in
Rivaroxaban has a half-life between 5 to 9 hours and renal clearance of 36%. Apixaban is 25% excreted through kidneys and its half-time is 12 hours. Finally, edoxaban the most recent Factor-Xa inhibitor exhibits a renal elimination of 50% and has a serum half-life of approximately 12 hours. Rivaroxaban (20 mg OD), edoxaban (60 mg OD) and apixaban (5mg BID) are recommended without any dose adjustment in patients with a CrCl > 50 mL/min. FDA has approved rivaroxaban 15 mg daily and edoxaban 30 mg daily in patients with CrCl 15-49 mL/min. A reduced dose of apixaban is recommended if two of three criteria are present: serum creatinine ≥ 1.5 mg/dl, age ≥ 80 years, body weight ≤ 60kg. The recommendation regarding a reduced dose of rivaroxaban (15mg) in CKD was based on a second analysis of the ROCKET-AF (15). Among patients with mild or moderate renal impairment rivaroxaban preserved the benefit of warfarin in preventing stroke and systemic embolism, while bleeding events were similar but fatal bleeding occurring less often with rivaroxaban (16). In respect to apixaban, a second analysis of the ARISTOTELE study (17), which included 3017 patients with CrCl of 25-50 mL/min showed a same efficacy of apixaban compared to warfarin in