February 23, 2015
2 min read

Dabigatran, rivaroxaban contraindicated in AF patients on dialysis

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More patients with atrial fibrillation on dialysis are using dabigatran or rivaroxaban, even though use of these agents are not recommended in this patient population, according to practice guidelines.

Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bioaccumulate to precipitate inadvertent bleeding. An observational study by Kevin E. Chan, MD, MSc, and colleagues, of the nephrology division at Massachusetts General Hospital, and the clinical research division of Fresenius Medical Care North America, both in Waltham, Mass., examined the prescription of dabigatran or rivaroxaban in the dialysis population.

Using data extracted from the Fresenius Medical Care North America End-Stage Renal Disease Database (ESRD), the researchers tracked the use of dabigatran (Pradaxa, Boehringer Ingelheim) and rivaroxaban (Xarelto, Janssen Pharmaceuticals) between October 2010 and October 2014, in 29,277 patients with AF who were undergoing dialysis. In their secondary analysis, Chan and colleagues followed a group of patients for 2 years to assess their bleeding and stroke outcomes. At baseline, they compared AF patients on warfarin (n = 8,064), aspirin (6,018), dabigatran (n = 281) and rivaroxaban (n = 244).

Within this study group, dabigatran was first prescribed 45 days after it received FDA approval in October 2010; the first rivaroxaban prescription came 161 days after FDA approval. Over the 4-year study, 3.1% of patients received dabigatran and 2.8% received rivaroxaban. The use of both drugs increased over time. Overall, 5.9% of patients on dialysis who require anticoagulants were prescribed dabigatran or rivaroxaban.  

The unadjusted event rates showed that patients prescribed dabigatran had a major bleeding rate of 83.1 events per 100 patient-years, patients prescribed rivaroxaban had a rate of 68.4 events per patient-years, while patients prescribed warfarin had a rate of 35.9 events per patient-years. Mortality rates from bleeding were as follows: dabigatran (19.2 deaths per 100 patient years), rivaroxaban (16.2) warfarin (10.2) and aspirin (7.7). The lowest rates for major and minor bleeding were seen in patients taking aspirin, according to the researchers.

Compared with warfarin, patients prescribed dabigatran (RR = 1.48, 95% CI, 1.21-1.81) and rivaroxaban (RR = 1.38, 95% CI 1.03-1.83) had a higher risk of major bleeding, the researchers wrote. The risk of hemorrhagic death was even greater for dabigatran (RR = 1.78, 95% CI 1.18-2.68) and rivaroxaban (RR = 1.71, 95% CI 0.93-3.12) when compared with warfarin. Patients treated with aspirin had the lowest rates of major and minor bleeding and hemorrhagic death.

“Our study is the first to evaluate these drugs in the dialysis population, and suggests concern given the increasing use of dabigatran and rivaroxaban in the ESRD population despite formal FDA warnings of caution in renal failure,” the researchers wrote. “In fact, our secondary analyses suggest excess morbidity and mortality from bleeding are associatively higher with dabigatran and rivaroxaban when compared to warfarin. Further studies are needed to evaluate how these drugs should be dosed when patients develop renal failure."

Disclosures: The researchers report no financial associations with the manufacturers of dabigatran and rivaroxaban. Chan reports receiving salary from Fresenius Medical Care North America but the company does not purchase or administer dabigatran, rivaroxaban or warfarin in its facilities. Please see the full study for a list of all other researchers' relevant financial disclosures.