Clinical Evidence for the Choice of the Direct Oral Anticoagulant in Patients with Atrial Fibrillation According to Creatinine Clearance

Abstract

Atrial fibrillation (AF) often coexists with chronic kidney disease (CKD), which confer to the patient a higher risk of both thromboembolic and hemorrhagic events. Oral anticoagulation therapy, nowadays preferably with direct oral anticoagulants (DOACs), represents the cornerstone for ischemic stroke prevention in high-risk patients. However, all four available DOACs (dabigatran, apixaban, rivaroxaban and edoxaban) are eliminated by the kidneys to some extent. Reduced kidney function facilitates DOACs accumulation and, therefore, different dose reductions are required, with slight differences between American and European recommendations especially in case of severe renal impairment (creatinine clearance < 30 mL/min). Overall, the use of DOACs in patients with non-end stage CKD and AF is effective similarly to warfarin, showing a better safety profile. The management of thromboembolic risk among patients with AF on dialysis remains challenging, as warfarin effectiveness for stroke prevention in this population is questionable and retrospective data on apixaban need to be confirmed on a larger scale. In kidney transplant recipients, DOACs may provide a potentially safer option compared to warfarin, but co-administration with immunosuppressants is a matter of concern.

Appropriateness of prescribing profiles and intake adherence to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: analysis of a retrospective longitudinal study using real-world data from Northern Portugal (AF-React Study)

“…A prudent approach is to check renal function at the initiation of treatment with NOACs, after 3 months and then every year, except for high-risk patients (the elderly >75 years, patients with low body mass) who require monitoring at least every 6 months 26. In patients with declining renal function, the current position of EHRA is to estimate the recheck intervals individually using a simple calculation: if CrCl is ≤60 mL/min, the recheck interval in months is CrCl/10 11…”

“…This is particularly relevant since the kidneys are responsible for partially eliminating all four available NOACs. Dabigatran has the greatest extent of renal elimination (80%), while 50%, 35% and 27% of edoxaban, rivaroxaban and apixaban, respectively, are cleared via the kidneys 11…”

Oral Anticoagulant Treatment in Patients with Atrial Fibrillation and Chronic Kidney Disease

“…Although the phase III trials excluded patients with severe renal impairment of a creatinine clearance (CrCl) < 25 to 30 mL/min, some cohort studies have demonstrated that NOACs also provide effective thromboprophylaxis in AF patients with mild to moderate renal dysfunction (CrCl of 30-79 mL/min) [44]. Adopted from [29,[38][39][40]45]. Legend: QD-once a day; BID-twice a day; P-gP-P glycoprotein transporter involved in absorption and renal clearance-plasma levels may be influenced by P-gP inducers or inhibitors; CYP450-cytochrome P 450 CYP3A4 involved in hepatic clearance-plasma levels may be affected by CYP3A4 inducers or inhibitors; Cmax-peak concentration; t1/2-half-life; INR-international normalized ratio.…”

“…Thus, assessment of the individual patient risks and regular monitoring of renal function is crucial to guide dose adjustments of NOACs [ 51 ]. It is important to note, that none of the NOACs have been approved in Europe for patients with CrCl < 15 mL/min or on dialysis [ 45 ].…”

“… Adopted from [ 29 , 38 , 39 , 40 , 45 ]. Legend: QD—once a day; BID—twice a day; P-gP—P glycoprotein transporter involved in absorption and renal clearance—plasma levels may be influenced by P-gP inducers or inhibitors; CYP450—cytochrome P 450 CYP3A4 involved in hepatic clearance—plasma levels may be affected by CYP3A4 inducers or inhibitors; Cmax—peak concentration; t1/2—half-life; INR—international normalized ratio.…”