Which oral anticoagulants can be used in CKD patients with atrial fibrillation

Which oral anticoagulants can be used in CKD patients with atrial fibrillation?

When the decision is made to anticoagulate, the 2014 American Heart Association and the 2016 European Society of Cardiology guidelines recommend warfarin as the oral anticoagulant of choice in patients with atrial fibrillation and advanced CKD or ESKD.

Warfarin has less than 1% kidney elimination, and should not accumulate with decreased kidney function or on dialysis. However, patients with advanced CKD and dialysis have alterations of their hepatic metabolism and tend to require lower doses of warfarin.

Non–vitamin K oral anticoagulants (NOACs), also referred to as direct oral anticoagulants, are increasingly being used in non-valvular atrial fibrillation. They include the direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban).

These drugs are at least non-inferior to warfarin in the prevention of thromboembolic complications of atrial fibrillation for the average patient. However, they have not been properly studied in advanced CKD and ESKD.

All NOACs are, to some extent, renally cleared, and may potentially accumulate in patients with a low GFR. This could lead to an increased risk for bleeding, especially since no clinically available coagulation parameter accurately estimates the level of anticoagulation.

As such, dosage adjustments are recommended in patients with CKD using the Cockcroft-Gault creatinine clearance formula. Using the body surface area standardized CKD-EPI GFR formula may lead to dosing error, as it is not in line with the randomized controlled trials used to make these suggestions.

Non Vitamin K Oral Anticoagulants


Warfarin
DabigatranApixabanRivaroxabanEdoxaban
Renal clearance<1%80%27%36%50%
Removal after 4 h of hemodialysis<1%50%–60%7%<1%9%

US Food and Drug Administration-Recommended Dosing of Non–Vitamin K Oral Anticoagulants by Creatinine Clearance

Creatinine Clearance mL/min (Cockcroft-Gault Equation)
>9051–9031–5015–30<15 OR ON DIALYSIS
Dabigatran a150 mg BID150 mg BID150 mg BID75 mg BIDNR
Apixaban b5 or 2.5 mg BID5 or 2.5 mg BID5 or 2.5 mg BID5 or 2.5 mg BID5 or 2.5 mg BID
Edoxaban c60 mg QD60 mg QD30 mg QD30 mg QDNR
Rivaroxaban20 mg QD20 mg QD15 mg QD15 mg QDNR

BID, Twice daily; QD, daily; NR, not approved by the FDA.

a Dabigatran is not approved in the rest of the world for CrCl 15 to 29 mL/min.

b Apixaban is only approved for CrCl <15 mL/min in the United States; 2.5 mg twice daily if the patient has any two of the following: serum creatinine ≥1.5 mg/dL, age ≥80 years, or body weight ≤60 kg.

c Not recommended in patients with eCrCl >95 mL/min due to high renal clerance.

Currently, the US Food and Drug Administration approved the use of apixaban for patients with a creatinine clearance <15 mL/min or on dialysis. Caution should still be exercised when using this medication, since these suggestions were based on small pharmacokinetic studies.

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