Comparisons between Novel Oral Anticoagulants and Vitamin K Antagonists in Patients with CKD

Abstract

Novel oral anticoagulants (NOACs) (rivaroxaban, dabigatran, apixaban) have been approved by international regulatory agencies to treat atrial fibrillation and venous thromboembolism in patients with kidney dysfunction. However, altered metabolism of these drugs in the setting of impaired kidney function may subject patients with CKD to alterations in their efficacy and a higher risk of bleeding. This article examined the efficacy and safety of the NOACs versus vitamin K antagonists (VKAs) for atrial fibrillation and venous thromboembolism in patients with CKD. A systematic review and meta-analyses of randomized controlled trials were conducted to estimate relative risk (RR) with 95% confidence interval (95% CIs) using a random-effects model. MEDLINE, Embase, and the Cochrane Library were searched to identify articles published up to March 2013. We selected published randomized controlled trials of NOACs compared with VKAs of at least 4 weeks' duration that enrolled patients with CKD (defined as creatinine clearance of 30-50 ml/min) and reported data on comparative efficacy and bleeding events. Eight randomized controlled trials were eligible. There was no significant difference in the primary efficacy outcomes of stroke and systemic thromboembolism (four trials, 9693 participants; RR, 0.64 [95% CI, 0.39 to 1.04]) and recurrent thromboembolism or thromboembolism-related death (four trials, 891 participants; RR, 0.97 [95% CI, 0.43 to 2.15]) with NOACs versus VKAs. The risk of major bleeding or the combined endpoint of major bleeding or clinically relevant nonmajor bleeding (primary safety outcome) (eight trials, 10,616 participants; RR 0.89 [95% CI, 0.68 to 1.16]) was similar between the groups. The use of NOACs in select patients with CKD demonstrates efficacy and safety similar to those with VKAs. Proactive postmarketing surveillance and further studies are pivotal to further define the rational use of these agents.

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

“…[165][166][167][168][169] A recent systematic review did not find that the newer agents were superior, but the point estimate for the risk of stroke was compatible with a substantial clinical benefit compared with warfarin despite a similar risk of bleeding ( Figure 5). 170,171 Additional trials are ongoing, and more information will soon be available.…”

Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations

“…The risk of major bleeding or the combined endpoint of major bleeding or clinically relevant non-major bleeding was similar between the groups. 41 A population-based nested case-control study in older patients with moderate CKD not on dialysis showed an increased risk for hemorrhage and that exposure to dabigatran or rivaroxaban was not associated with a statistically significant increased risk of major hemorrhagic events as compared to warfarin. 42 A limitation of the study was that only an algorithm was used to detect patients with CKD with missing individual GFR estimations.…”

Assessment of Direct Oral Anticoagulant Prescribing and Monitoring Pre- and Post-Implementation of a Pharmacy Protocol at a Community Teaching Hospital

“…A subgroup analysis of patients with moderate renal impairment (CrCl 30-50 mL/min) indicated that when dosed according to the manufacturers' recommendations, DOACs are at least as safe as warfarin. 16,17 Dose adjustments are also warranted based on indication, age, and weight and can be further complicated by the addition of interacting drugs. Additionally, not all DOACs are approved for the same indications as VKAs.…”