DOACs Used in Dialysis Patients, but Little Research Has Been Done

Dialysis patients with atrial fibrillation (AF) are often treated with direct oral anticoagulants (DOACs), but these drugs have not been studied enough in this population. A new study has found that while most dialysis/AF patients are treated with warfarin, just under 8% are treated with DOACs, with the percentage rising.

"Overall use of DOACs in dialysis patients with AF is increasing rapidly and exceeded over one-quarter of prescriptions in 2015. This highlights the need for further study of these drugs in this complex population that is typically excluded from clinical trials,” Konstantinos Siontis, MD, Cardiology Fellow at the University of Michigan, and his colleagues wrote in their abstract, published in the journal Circulation. Their research was presented at the American Heart Association’s Scientific Sessions 2017 meeting, held in Anaheim in November.

Patients with end-stage renal disease (ESRD) on dialysis are usually excluded from randomized controlled trials that lead to the approval of most medications. “This is also the case for anticoagulants in AF,” Siontis told Drug Topics. “The implications are particularly important in the dialysis population, because these patients have generally higher risks of stroke as well as treatment-related bleeding.”

Siontis and his colleagues identified eligible dialysis patients who were enrolled in the comprehensive U.S. Renal Data System database from October 2010 through December 2015. The patients had been prescribed apixaban (Eliquis, Bristol-Myers Squibb), rivaroxaban (Xarelto, Janssen), dabigatran (Boehringer Ingelheim), or warfarin (Coumadin).

From a population of more than 1.3 million patients with ESRD, the study identified 21,593 dialysis patients with a diagnosis of AF and who had a prescription for oral anticoagulation. They found that 92% of patients were prescribed warfarin only, while 7.8% of patients were prescribed the DOACs apixaban, dabigatran, and rivaroxaban.

During the study period, the rate at which DOACs were used increased greatly relative to warfarin, rising from 0.16% to 29.16%. Apixaban accounted for the majority of new DOAC prescriptions. “Patients on DOACs and warfarin had comparable risk profiles, prevalence of cerebrovascular disease, and CHA₂DS₂Vasc scores,” Siontis and his colleagues wrote.

Siontis believes the way that DOACs are studied in dialysis patients with AF needs to change. While there is some limited pharmacokinetic data on the use of the DOACs in dialysis patients, their manufacturers do not make formal dosing recommendations because they have not been studied specifically in dialysis patients, Siontis said. “The finding that so many dialysis patients in the real world are prescribed medications that do not have clear data on safety and effectiveness is thought-provoking.”

This study is only a step in evaluating DOACs in the dialysis population, since it provides an understanding of current usage patterns, Siontis said. “The next important question that we aim to address is, ‘What are the outcomes associated with the use of the DOACs in dialysis patients?’  The results of that investigation may help guide future decision-making in the treatment of this challenging patient population.”

Future randomized controlled trials will also be critical in determining the outcomes associated with the use of DOACs in dialysis patients, Siontis added.