Non-vitamin-K-dependent Oral Anticoagulants in End-stage Renal Disease Patients with Non-valvular Atrial Fibrillation: An Impossible Wedding?

Abstract

Atrial fibrillation (AF) is the most common arrhythmia in patients with chronic kidney disease (CKD). In this population, AF is associated with an increased risk of thromboembolism and stroke as a result of a progressive decline in the glomerular filtration rate. However, CKD patients, in particular those on renal replacement therapy, also have an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting an increased risk of stroke. Limited evidence of its efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD have often resulted in the underuse of anticoagulation in CKD patients. A large body of evidence suggests that non-vitamin-K-dependent oral anticoagulants (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage and mortality. Hence, they are currently recommended for patients with AF at risk of stroke. However, the metabolism of NOACs is largely dependent on the kidneys for elimination and little is known about their use in patients with creatinine clearance <25 mL/min, who have been excluded from all pivotal phase III NOAC trials. This review focuses on the current pharmacokinetic, observational and prospective data on NOACs in patients affected by moderate to advanced CKD (creatinine clearance 15–49 mL/min) and in those on dialysis (Cardionephrology)