Nonvitamin K-dependent oral anticoagulants (NOACs) in chronic kidney disease patients with atrial fibrillation

• Published in: Thrombosis research Vol. 155; pp. 38 - 47
• Main Authors: Di Lullo, L, Ronco, C, Cozzolino, M, Russo, D, Russo, L, Di Iorio, B, De Pascalis, A, Barbera, V, Galliani, M, Vitaliano, E, Campana, C, Santoboni, F, Bellasi, A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01-07-2017
• Subjects: Administration, Oral; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Anticoagulants - pharmacokinetics; Anticoagulants - therapeutic use; Anticoagulation therapy; Atrial fibrillation; Atrial Fibrillation - complications; Atrial Fibrillation - drug therapy; Chronic kidney disease; Dabigatran - administration & dosage; Dabigatran - adverse effects; Dabigatran - pharmacokinetics; Dabigatran - therapeutic use; Hematology, Oncology and Palliative Medicine; Hemorrhage - chemically induced; Humans; Nonvitamin K-dependent oral anticoagulants (NOACs); Prospective Studies; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - pharmacokinetics; Pyrazoles - therapeutic use; Pyridines - administration & dosage; Pyridines - adverse effects; Pyridines - pharmacokinetics; Pyridines - therapeutic use; Pyridones - administration & dosage; Pyridones - adverse effects; Pyridones - pharmacokinetics; Pyridones - therapeutic use; Renal Insufficiency, Chronic - complications; Rivaroxaban - administration & dosage; Rivaroxaban - adverse effects; Rivaroxaban - pharmacokinetics; Rivaroxaban - therapeutic use; Stroke - etiology; Stroke - prevention & control; Thiazoles - administration & dosage; Thiazoles - adverse effects; Thiazoles - pharmacokinetics; Thiazoles - therapeutic use; Thromboembolism - etiology; Thromboembolism - prevention & control; Warfarin; Warfarin - administration & dosage; Warfarin - adverse effects; Warfarin - pharmacokinetics; Warfarin - therapeutic use; Warfarin; Chronic kidney disease; Anticoagulation therapy; Nonvitamin K-dependent oral anticoagulants (NOACs); Atrial fibrillation
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2017.04.027

Abstract Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance < 25 ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with moderate to advanced chronic kidney disease (creatinine clearance 15–49 ml/min) and those on dialysis.