In CKD and Afib, Which Anticoagulant Is Best?

So-called NOACs — novel oral anticoagulants not in the warfarin class — may be preferred for people with early stages of chronic kidney disease at risk for thrombotic events, according to a meta-analysis.

Based on high-certainty evidence, NOACs were superior to vitamin K antagonists (VKAs) such as warfarin for reducing the risk for stroke or systemic embolism in people with atrial fibrillation (AF) and chronic kidney disease (risk ratio 0.79, 95% CI 0.66-0.93), Sunil Badve, PhD, of The George Institute for Global Health in Australia and colleagues reported in Annals of Internal Medicine.

In the review of 45 trials, use of high-dose NOACs for anticoagulation was also tied to lower rates of hemorrhagic stroke versus VKAs in the patient population with chronic kidney disease (RR 0.48, 95% CI 0.30-0.76), based on moderate-certainty evidence. Similarly, high-dose NOAC therapy reduced to relative risk for intracranial hemorrhage by 51% (RR 0.49, 95% CI 0.30-0.80), also based on moderate-certainty evidence.

However, Badve’s group only found low-certainty evidence on outcomes of anticoagulation therapies for recurrent venous thromboembolism (VTE) or VTE-related mortality, failing to show a difference between NOACs and VKAs. However, NOACs did markedly reduce the risk for recurrent VTE or VTE-related death when compared with placebo alone (RR 0.14, 95% CI 0.04-0.48). Although the group also found evidence suggesting NOACs may lower the risk for major bleeding compared with VKAs, this evidence was also of very low certainty.

It also remained unclear which anticoagulant therapy was more beneficial for reducing the risk of myocardial infarction, all-cause death, gastrointestinal bleeding, and fatal or minor bleeding.

The review and meta-analysis looked at 45 trials, representing over 34,000 patients. Eleven of these trials involved patients with atrial fibrillation and those with chronic kidney disease not dependent on dialysis.

Calling the review “ambitious,” an accompanying editorial by Ainslie Hildebrand, MD, MSc, of the University of Alberta in Canada, and colleagues pointed out that these findings are similar to what’s seen in the general population: “compared with VKAs, NOACs reduced the risk for stroke or systemic embolism and hemorrhagic stroke but without a significantly reduced risk for bleeding in patients with early CKD (that is, creatinine clearance >25 mL/min) and AF.”

“Despite the tremendous burden of disease in patients with advanced CKD and [end-stage kidney disease], they have historically been excluded from trials of VKAs and NOACs for prevention and treatment of VTE as well as for prevention of stroke and systemic embolism in AF,” the editorialists noted, as only eight trials included in the meta-analysis assessed outcomes in dialysis-dependent end-stage kidney disease.

Also, none of the 11 trials involving patients with atrial fibrillation included those with advanced stage, dialysis-dependent end-stage kidney disease. Badve’s group also highlighted this point by calling for more randomized trials evaluating anticoagulant therapy benefits specifically in a population with AF and advanced chronic kidney disease.

The editorialists noted that “two highly anticipated ongoing studies” looking at patients with atrial fibrillation and end-stage kidney disease — RENAL-AF (RENal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) and AXADIA — will soon help answer some of these lingering uncertainties that this review wasn’t able to answer, like whether anticoagulant therapy in those with advanced kidney disease requires an individualized approach to balance benefits and risks.