A large, retrospective study comparing first-time users of rivaroxaban and dabigatran suggests that rivaroxaban poses a higher risk of bleeding in elderly patients with nonvalvular atrial fibrillation (NVAF).
Treatment with rivaroxaban was associated with significant increases in intracranial hemorrhage (ICH) and major extracranial bleeding, a nonsignificant reduction in thromboembolic stroke, and a nonsignificant increase in mortality.
David J. Graham, MD, of the US Food and Drug Administration in Silver Spring, Maryland, and his colleagues reported these results in JAMA Internal Medicine.
The investigators analyzed 118,891 NVAF patients older than 65 who were enrolled in Medicare. The patients had started treatment with dabigatran (150 mg twice daily) or rivaroxaban (20 mg once daily) from November 4, 2011, through June 30, 2014.
There were 52,240 patients receiving dabigatran and 66,651 receiving rivaroxaban.
The study’s primary outcomes were thromboembolic stroke, ICH, major extracranial bleeding events (including major gastrointestinal bleeding), and mortality.
The investigators adjusted for differences in baseline characteristics and calculated hazard ratios (HRs) for the primary outcomes. They also calculated adjusted incidence rate differences.
The data showed that, compared to patients who received dabigatran, those who received rivaroxaban had:
- 1.8 fewer cases of thromboembolic stroke per 1000 person-years (HR=0.81; 95% CI, 0.65-1.01; P=0.07)
- 2.3 excess cases of ICH per 1000 person-years (HR=1.65; 95% CI, 1.20-2.26; P=0.002)
- 13.0 excess cases of major extracranial bleeding per 1000 person-years (HR=1.48; 95% CI, 1.32-1.67; P<0.001)
- 9.4 excess cases of major gastrointestinal bleeding per 1000 person-years (HR=1.40; 95% CI, 1.23-1.59; P<0.001)
- 3.1 excess deaths per 1000 person-years (HR=1.15; 95% CI, 1.00-1.32; P=0.051).
The investigators noted that this study had several limitations. The mean follow-up time was 4 months, which led to a smaller sample size at longer durations of use.
In addition, the study was restricted to patients age 65 and older. Although this age group accounts for 80% of patients with NVAF, the comparative effects of treatment with dabigatran and rivaroxaban could be different in younger populations.
Because the study was observational, it may also be subject to residual confounding by unmeasured factors.
And finally, the investigators examined warfarin-naïve, first-time users of dabigatran and rivaroxaban. Results could differ in patients switching from warfarin to a novel oral anticoagulant.
