Non-vitamin K oral anticoagulants appear superior to vitamin K antagonists in early-stage CKD

Non-vitamin K oral anticoagulants (NOACs) appear to have a better risk-benefit profile than vitamin K antagonists (VKAs) in patients with early-stage chronic kidney disease (CKD), according to a recent systematic review and meta-analysis.

Patients who have advanced CKD or end-stage kidney disease (ESKD) and atrial fibrillation receive oral anticoagulant therapy less frequently than patients who have normal kidney function, and patients with CKD have been excluded from most trials of anticoagulation. To determine the benefits and harms of anticoagulant therapy in adults with stages 3 to 5 CKD, including dialysis-dependent ESKD, researchers analyzed randomized controlled trials that evaluated any use of VKAs or NOACs in patients with CKD and reported efficacy or bleeding outcomes. The results were published July 16 by Annals of Internal Medicine.

Forty-five trials with 34,082 patients were included in the analysis. The median sample size was 276 patients, and the median follow-up was 12 months. Of the 45 trials, 11 included 16,787 patients with atrial fibrillation, 11 involved 2,975 patients with acute venous thromboembolism, six involved 3,908 medically ill or perioperative patients who required thromboprophylaxis, eight involved 865 patients with dialysis-dependent ESKD, and nine included 9,727 patients with cardiovascular disease other than atrial fibrillation. Patients with a creatinine clearance below 20 mL/min or an estimated glomerular filtration rate below 15 mL/min/1.73 m² were excluded from all trials except the eight trials examining dialysis-dependent ESKD.

In patients with atrial fibrillation, NOACs were associated with reduced risks for stroke or systemic embolism (risk ratio [RR], 0.79; 95% CI, 0.66 to 0.93; high-certainly evidence) and hemorrhagic stroke (RR, 0.48; 95% CI, 0.30 to 0.76; moderate-certainty evidence) versus VKAs. However, the effects of NOACs versus VKAs on recurrent venous thromboembolism or deaths related to venous thromboembolism were uncertain (RR, 0.72; 95% CI, 0.44 to 1.17; low-certainty evidence). NOACs appeared to reduce major bleeding risk versus VKAs in all trials combined (RR, 0.75; 95% CI, 0.56 to 1.01; low-certainty evidence), but this finding was not significant and no difference was observed in major bleeding risk.

The authors noted that their analysis was limited by exclusion of patients with ESKD and advanced CKD from many trials, lack of individual-patient data, and underreporting of data on organ-specific bleeding, among other factors. However, they concluded that based on their results, NOACs appear to have a better benefit-risk profile than VKAs in patients with early-stage CKD, significantly reducing stroke or systemic embolism and hemorrhagic stroke in atrial fibrillation. They noted that the available evidence was not sufficient to recommend wide use of VKAs or NOACs in patients with advanced disease and called for adequately powered randomized trials to examine benefits and harms of anticoagulation in this population.

An accompanying editorial reiterated that patients with advanced kidney disease have historically been excluded from trials of VKAs and NOACs but said that the current review supports a superior benefit profile of NOACs in patients with early CKD and atrial fibrillation.

“Assuming this result reflects the truth and recognizing the limitations of subgroup analysis, is there a level of renal dysfunction for which clinicians should apply greater caution in extrapolating these findings?” the editorialists asked. The evidence to date on this question is inconclusive, they said, noting that proof of efficacy must wait for the completion of two ongoing studies in patients with atrial fibrillation and ESKD. “Until the results of these trials become available,” the editorialists wrote, “the decision to use anticoagulant therapy in patients with ESKD will continue to require an individualized approach that balances potential benefits and harms.”