Off-label dabigatran, rivaroxaban use with dialysis creates concerns

The number of atrial fibrillation patients on dialysis given novel oral anticoagulants is growing. Research shows that dabigatran and rivaroxaban are increasingly being used by patients with atrial fibrillation on dialysis, despite concerns about creatinine clearance in this population.

A research team led by Kevin E. Chan, MD, MSc, from the Clinical Research Division of Fresenius Medical Care North America in Waltham, Mass., explored trends on usage of oral anticoagulants in a database of chronic dialysis patients. Fresenius Medical Care North America’s End-Stage Renal Disease database represents 30 percent of Americans on chronic dialysis. In all, 29,977 patients on dialysis also had atrial fibrillation between 2010 and 2014.

Chan and colleagues found that of these patients, 3.1 percent took dabigatran (Pradaxa, Boehringer Ingleheim) and 2.8 percent took rivaroxaban (Xarelto, Janssen Pharmaceuticals), both increasing over time. They noted that the first report of dabigatran among the cohort was 45 days following U.S. availability. For rivaroxaban, it was 161 days following FDA approval.

More than three-quarters of dabigatran prescriptions were reduced dosage. Meanwhile, among prescriptions of rivaroxaban, more than half of patients received reduced dosage.

Current labeling suggests that reduced dosage be used in patients with partial kidney function; however, Chan et al noted that rivaroxaban, being bound to protein, was not cleared by dialysis.

In unadjusted analysis, major bleeding occurred at rates of 83.1 and 68.4 per 100 patient years for dabigatran and rivaroxaban, respectively. For warfarin, there were 35.9 major bleeding events per 100 patient years. Dabigatran, rivaroxaban, warfarin and aspirin had 19.2, 16.2, 10.2 and 7.7 deaths per 100 patient-years, respectively.

Risk for death by hemorrhage among patients taking dabigatran or rivaroxaban was 1.78 and 1.71, respectively, compared with warfarin, after adjustment. Risk for major bleeding on dabigatran and rivaroxaban was 1.48 and 1.38. However, risk for hemorrhagic stroke was four times higher among patients taking warfarin than dabigatran. No hemorrhagic strokes were reported for patients on rivaroxaban.

They found aspirin had a reduced risk of major or minor bleeding or hemorrhagic death compared to warfarin (0.78, 0.39 and 0.42, respectively).

Ultimately, Chan et al suggested caution and further study of the effects of novel oral anticoagulation for atrial fibrillation patients on dialysis.

The study was published online Jan. 16 in Circulation.