Anticoagulation in Patients with Chronic Kidney Disease

Abstract

Background: Both atrial fibrillation and venous thromboembolism (VTE) are highly prevalent among patients with chronic kidney disease (CKD). Until recently, warfarin was the most commonly prescribed oral anticoagulant. Direct oral anticoagulants (DOACs) have important advantages and have been shown to be noninferior to warfarin with respect to stroke prevention or recurrent VTE in the general population, with lower bleeding rates. This review article will provide available evidence on the use of DOACs in patients with CKD.

Summary: In post hoc analyses of major randomized studies with DOACs for stroke prevention in atrial fibrillation, in the subgroup of participants with moderate CKD, defined as a creatinine clearance (CrCl) of 30-50 mL/min, dabigatran 150 mg and apixaban were associated with lower rates of stroke and systemic embolism, whereas apixaban and edoxaban were associated with lower bleeding and mortality rates, compared with warfarin. In retrospective observational studies in patients with advanced CKD (defined as a CrCl <30 mL/min) and atrial fibrillation, DOACs had similar efficacy with warfarin with numerically lower bleeding rates. All agents warrant dose adjustment in moderate-to-severe CKD. In patients on maintenance dialysis, the VALKYRIE trial, which was designed initially to study the effect of vitamin K on vascular calcification progression, established superiority for rivaroxaban compared with a vitamin K antagonist (VKA) in the extension phase. Two other clinical trials using apixaban (AXADIA and RENAL-AF) in this population were inconclusive due to recruitment challenges and low event rates. In post hoc analyses of randomized studies with DOACs in patients with VTE, in the subgroup of participants with moderate CKD at baseline, edoxaban was associated with lower rates of recurrent VTE, whereas rivaroxaban and dabigatran were associated with lower and higher bleeding rates, respectively, as compared to warfarin.

Key messages: DOACs have revolutionized the management of atrial fibrillation and VTE, and they should be preferred over warfarin in patients with moderate-to-severe CKD with appropriate dose adjustment. Therapeutic drug monitoring with a valid technique may be considered to guide clinical management in individualized cases. Current evidence questions the need for oral anticoagulation in patients on maintenance dialysis with atrial fibrillation as both DOACs and VKAs are associated with high rates of major bleeding.

Keywords: Atrial fibrillation; Chronic kidney disease; Direct oral anticoagulants; Pharmacokinetics; Venous thromboembolism; Warfarin.

Fig. 1.

Mechanism of action of oral anticoagulants. Modified from Mavrakanas and Bounameaux [4]. DOACs, direct oral anticoagulants; Vit K, vitamin K; VKORC 1, vitamin K epoxide reductase complex subunit 1.

Fig. 2.

Dosing recommendations based on available data and expert opinion for DOACs in patients with CKD. Color guide: green – recommended; yellow – suggested; orange – very limited data, use with caution after considering risks and benefits; red – no data or formal contraindication, do not use. bid, twice daily; CrCl, creatinine clearance; LMWH, low-molecular-weight heparin; qd, once daily; RRT, renal replacement therapy.