Still Seeking Answers for Safe Anticoagulation in Patients on Hemodialysis

Volume 22, Issue 2

Patients with end-stage kidney disease (ESKD) frequently have many cardiovascular comorbidities. Longstanding hypertension and diabetes are common causes of ESKD; unfortunately, both of these diseases also increase the risk of atrial fibrillation (AF) as well as the risk of stroke in patients who develop AF. Hence, many patients with ESKD and AF will be candidates for chronic oral anticoagulation therapy.

While the direct acting oral anticoagulants (DOACs) have supplanted warfarin for the majority of patients with AF who require oral anticoagulation, their benefit in patients with ESKD remains uncertain. In this week’s issue of Talking Therapeutics, we explore some new data evaluating the safety and efficacy of DOACs vs warfarin in patients with ESKD.

Point 1: Jury Still Out

In the RENAL-AF study, patients were randomized to receive apixaban or dose-adjusted warfarin. Apixaban was administered at a dosage of 2.5 mg twice daily among participants who were at least 80 years of age, weighed at least 60 kg, or met both criteria; the remaining patients received 5 mg of apixaban twice daily. Unfortunately, the trial was stopped prematurely after only about 150 patients were enrolled.

At 1 year, the rates for major or clinically relevant nonmajor bleeding were 32% and 26% in the apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63 to 2.30]). However, rates of stroke or systemic embolism were similar, at 3.0% and 3.3% for each respective group.

The time in the therapeutic range (international normalized ratio, 2.0 to 3.0) for patients treated with warfarin was 44% (interquartile range, 23% to 59%), which is much lower than other contemporary DOAC trials in non-ESKD patient populations.

Because of the low enrollment, this trial was not powered to determine any difference in either the safety or efficacy of apixaban vs warfarin in patients with ESKD.

Point 2: Should We Do Anything?

This trial showed the rates for bleeding were 10 times higher than the rates for stroke or systemic embolism. This highlights that a placebo group in this trial would have been very helpful to investigate whether the risks of anticoagulation are worth the potential benefits in this at-risk patient population.