NOACs best for Afib in early kidney disease, but jury out in advanced CKD

For patients with early-stage chronic kidney disease (CKD) who have atrial fibrillation, non-vitamin K oral anticoagulants (NOACs) have a better benefit-risk profile than vitamin K antagonists (VKAs), according to a large meta-analytic review of published studies.

But for advanced CKD or end-stage renal disease (ESRD), there is not enough evidence to establish the benefits or harms of either approach to anticoagulation, the research team says.

The study, from Dr. Sunil Badve from The George Institute for Global Health in New South Wales, Australia and colleagues, was published online today in Annals of Internal Medicine.

The investigators note that CKD is a prothrombotic state associated with increased risk for atrial fibrillation and venous thromboembolism (VTE), and anticoagulant therapy is important for prevention of stroke and systemic embolism. However, patients with CKD are generally excluded from most trials evaluating anticoagulants.

For the new analysis, they reviewed 45 randomized controlled trials with 34,082 participants evaluating VKAs or NOACs for any indication in patients with CKD stages 3 to 5, including those with dialysis-dependent ESRD. The indication was atrial fibrillation in 11 trials, VTE in 11 trials, thromboprophylaxis in six trials, prevention of dialysis access thrombosis in eight trials and cardiovascular disease other than atrial fibrillation in nine trials.

In atrial fibrillation, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio, 0.79; 95% CI, 0.66 to 0.93) with "high-certainty" evidence and hemorrhagic stroke (RR, 0.48; 95% CI, 0.30 to 0.76) with "moderate-certainty" evidence, the investigators report.

The effects of NOACs (vs VKAs) on recurrent VTE or VTE-related death were uncertain (RR, 0.72; 95% CI, 0.44 to 1.17), albeit based on "low-certainty" evidence.

In all trials combined, NOACs "seemingly" reduced major bleeding risk compared with VKAs (RR, 0.75; 95% CI, 0.56 to 1.01; low- certainty evidence), suggesting that patients with CKD will derive "similar or greater" benefit compared with patients without CKD, the investigators say.

The evidence is "insufficient to recommend widespread use of VKAs or NOACs to improve clinical outcomes in patients with advanced CKD and dialysis-dependent ESKD. Adequately powered randomized trials are required to evaluate the benefits and harms of anticoagulant therapy in this patient population," they conclude.

The authors of a linked editorial note that a recent retrospective cohort study of patients with ESRD and atrial fibrillation found no difference in the risk for stroke or systemic embolism between patients taking a NOAC (apixaban) or a VKA (warfarin), "raising concerns that these medications might be all risk and no benefit, at least for prophylaxis."

Dr. Deborah Zimmerman from University of Ottawa and colleagues say two "highly anticipated" ongoing studies in patients with AF and ESRD (RENAL-AF and AXADIA) are required to prove efficacy. "Until the results of these trials become available, the decision to use anticoagulant therapy in patients with (ESRD) will continue to require an individualized approach that balances potential benefits and harms," they conclude in their editorial.

"In patients with early stages of CKD and atrial fibrillation who need anticoagulation for stroke prevention, high dose NOACs should be considered over warfarin," Dr. Badve said by email. "NOACs may

be a reasonable treatment option for patients with CKD who develop acute venous thromboembolism. However, there is insufficient evidence to conclude whether patients with advanced stages of CKD including those requiring dialysis derive benefit from VKA or NOAC. In these patients, treatment should be based on individual risk-benefit assessment."

The study had no specific funding. Dr. Badve has received personal fees from Bayer AG and Amgen Australia, and nonfinancial support from Bayer AG during the conduct of the study.

SOURCE: http://bit.ly/2G9aF7x and http://bit.ly/2G9aIQL

Ann Intern Med 2019.