The Use of Novel Oral Anticoagulants in Atrial Fibrillation patients with Chronic Kidney Disease
Introduction
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Dose Modification of NOACS
age 80 years or older, body weight 60 kg or less, or serum creatinine 1.5 mg/dL or more.
Atrial fibrillation is an important risk factor for stroke and systemic embolism. Vitamin K antagonists (VKAs) have long been the standard of care in patients at risk for thromboembolic complications, but physicians are increasingly reluctant to prescribe these drugs as they increase bleeding risk. Impaired renal function is associated with a higher prevalence of atrial fibrillation (AF) and with an increased risk of thromboembolic events in patients with nonvalvular AF. Current guidelines recommend treatment with oral anticoagulants for AF patients at risk for stroke; however, impaired renal function also confers a substantially increased risk of major bleeding and often contributes to underutilization of oral anticoagulation therapy in AF populations.
- The second new alternative administered at a dose of 20 mg daily.
- 15 mg daily if the CrCl is < 50 mL/min.
- The drug is contraindicated in severe renal impairment (CrCl < 15 mL/min) or advanced liver disease.
- Administered at a dose of 150 mg b.i.d or 110 mg b.i.d,
- 75 mg b.i.d in the presence of renal insufficiency [creatinine clearance (CrCl) < 50 mL/min].
- The drug is contraindicated in patients with severe renal impairment (CrCl < 30 mL/min) or advanced liver disease
- Administered at a dose of 60 mg daily.
- 30 mg daily if the CrCl is < 50 mL/min or body weight is less than 60 kg.
- The drug is contraindicated in severe renal impairment (CrCl < 15 mL/min) and advanced liver disease
NOACs use at different CrCL levels
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Crcl
< 15 ml/min or on HD
Apixaban
chosen as its mode of excretion is mainly via the bile; theoretically enabling stable plasma levels independent of HD
Rivaroxaban
An estimated 33% of active drug of rivaroxaban is eliminated by kidney so it is usually avoided in patients with crcl < 15 ml/min.
Dabigatran
HD patients had a higher risk of major bleeding
Mortality because of bleeding was higher in the HD patients
Edoxaban
a lower major bleeding incidence rate of 4% per year a lower composite of stroke, Systemic embolism.
Crcl
15-29 ml/min or on HD
Dabigatran
The US Food and Drug Administration (FDA) has approved dabigatran in a dosage of 75 mg twice daily for atrial fibrillation patients with stage IV CKD based on pharmacodynamic modelling studies.
Rivaroxaban
Rivaroxaban 15 mg/d has been approved by the US FDA and European Medicines Agency for atrial fibrillation patients with stage IV CKD
Crcl
>30 ml/min
Apixaban
5mg twice daily in patients with atrial fibrillation with less bleeding and lower mortality
Rivaroxaban
significantly reduced rate of stroke with the 150mg twice daily dose compared with warfarin, and with a similar rate of major hemorrhage.
Dabigatran
A reduction in intracranial hemorrhage with rivaroxaban compared with warfarin was evident in those with reduced eCrCl given rivaroxaban 15mg daily
NOACs Antidotes
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Idarucizumab (aDabiFab,
Andexanet alfa
(r-Antidote, PRT064445, PRT4445)
PER977 (Aripazine, Ciraparantag)
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NOACs Monitoring