Novel oral anticoagulants and the risk of major hemorrhage in elderly patients with chronic kidney disease: a nested case-control study

Background — The novel oral anticoagulants including dabigatran and rivaroxaban differ in their degree of kidney excretion.

Methods — We conducted a population based nested case-control study among patients 66 years and older with CKD (excluding patients on chronic dialysis) who received an oral anticoagulant between April 2006 and March 2013. We calculated odds ratio for hospitalization with a major hemorrhagic event and receipt of dabigatran, rivaroxaban or warfarin in the preceding 60 days. We also performed a sensitivity analysis to investigate whether a relationship exists between major hemorrhage and advanced age (age <80 years or ≥80 years).

Results — We identified 237,409 patients with CKD, of whom 4470 (1.9%) experienced a major hemorrhage. We matched these cases to 14,460 control patients. Use of dabigatran or rivaroxaban was not associated with a statistically significantly elevated risk of hemorrhage compared to warfarin (adjusted odds ratio (aOR) 1.15, 95% confidence interval (CI) 0.91 to 1.45 for dabigatran, aOR 1.22; 95% CI 0.83 to 1.79 for rivaroxaban). Our sensitivity analysis found that older age was associated with an increased risk of hemorrhage for patients on dabigatran; (aOR 1.41; 95% CI 1.06-1.88) results were similar but did not reach statistical significance for rivaroxaban (aOR 1.57; 95% CI 0.91-2.69).

Conclusions — Among elderly patients with CKD, exposure to dabigatran or rivaroxaban was not associated with a statistically significant increased risk of major hemorrhagic events compared to warfarin.