NOACs Show Superiority in Early-Stage Chronic Kidney Disease

Non-vitamin K oral anticoagulants (NOACs) appear to have a risk-benefit profile superior to that of vitamin K antagonists (VKAs) for the treatment of atrial fibrillation in patients with early-stage chronic kidney disease, according to a recent systematic review and meta-analysis.¹

In these patients, NOACs significantly decreased the risk for stroke or systemic embolism by 21%, the risk for hemorrhagic stroke by 52%, and that for intracranial hemorrhage by 51% compared with VKAs, a team led by Sunil V. Badve, PhD, from The George Institute for Global Health at University of New South Wales Medicine in Newtown, Australia, reported in the Annals of Internal Medicine.

NOACs decreased the risk for recurrent venous thromboembolism (VTE) or VTE-related death by 28% and the risk for major bleeding by 25% compared with VKAs, but the reductions were nonsignificant.

The systematic review and meta-analysis included 45 randomized controlled trials involving 34,082 participants who received anticoagulation for atrial fibrillation (11 trials), VTE (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and non-atrial fibrillation cardiovascular disease (9 trials).

To be included in the study, patients needed to have a creatinine clearance below 60 mL/min, an estimated glomerular filtration rate below 60 mL/min/1.73 m², or dialysis-dependent end-stage renal disease. The investigators considered a creatinine clearance above 25 mL/min to be early-stage chronic kidney disease (CKD).

“This review provides a comprehensive overview of available data describing the effects of anticoagulation for patients with CKD and a range of comorbidities or other risk factors,” Dr Badve and collaborators wrote. “It identifies clear findings that can be used to guide treatment but also several areas where data are inadequate and further studies are urgently required.”

Strengths of the systematic review included the large number of participants, the robust evaluation of efficacy and bleeding outcomes, and use of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the body of evidence, the authors noted. The investigators also acknowledged limitations of their analysis, including little evidence for advanced CKD or end-stage renal disease and the use of data mostly from subgroups of large trials.

In an accompanying editorial,² Deborah Zimmerman, MD, from the University of Ottawa, Ontario, Canada, and coauthors commented: “In this systematic review, NOACs had similar effectiveness to VKAs for prevention of recurrent VTE and VTE-related death and similar efficacy to placebo for thromboprophylaxis in early CKD. However, it does support the superior benefit profile of NOACs without additional risks compared with VKAs for patients with early CKD and [atrial fibrillation].”

References

1. Ha JT, Neuen BL, Cheng LP, et al. Benefits and harms of oral anticoagulant therapy in chronic kidney disease. Ann Intern Med. 2013;62:615-632.
2. Hildebrand A, Ribic C, Zimmerman D. Balancing the benefits and harms of oral anticoagulation in chronic kidney disease: What does the available evidence tell us? Ann Intern Med. 2019. doi:10.7326/MP19-1504