1. Based on a retrospective cohort study of US Medicare patients, rivaroxaban was associated with a significantly increased risk of intracranial and extracranial hemorrhage compared with dabigatran when used in elderly patients with nonvalvular atrial fibrillation for stroke prevention.
2. There was a trend towards a decrease in thromboembolic stroke associated with rivaroxaban, however the absolute increase in bleeding exceeded the decreased rate of stroke.
Evidence Rating Level: 2 (Good)
Study Rundown: Dabigatran and rivaroxaban are both non-vitamin K oral anticoagulants (NOAC) that are approved for use in stroke prevention in nonvalvular atrial fibrillation (AF), however these two medications have not been compared against each other. This retrospective cohort study aimed to compare the risks of thromboembolism, bleeding, and mortality in patients with nonvalvular AF on dabigatran versus rivaroxaban.
Rivaroxaban was associated with significantly increased risk of intracranial and extracranial bleeding (including major gastrointestinal bleeding) as compared to dabigatran. Rivaroxaban also had a non-significant decrease in thromboembolic stroke, however the absolute increase in hemorrhage with rivaroxaban exceeded this reduction in stroke. Strengths of this study included the large population based study and having only new users of the anticoagulants to limit the time on anticoagulation as a confounding variable. Limitations included the retrospective nature of the study, relatively short mean duration of follow-up of 4 months. It would also be of interest to study the apixaban, as studies have shown it to have a decreased bleeding risk and decreased risk of thromboembolic stroke.
Relevant Reading: Apixaban versus Warfarin in Patients with Atrial Fibrillation
In-Depth [retrospective cohort study]: This retrospective cohort study included patients older than 65, enrolled in fee-for-service Medicare, with nonvalvular AF and who were started on dabigatran or rivaroxaban from November 2011 to June 2014. Patients were excluded if they had ever been on warfarin or another NOAC previously, lived in a nursing home or had a diagnosis where they may have been on anticoagulation for another reason in the past six months prior to study inception. The exposures of interest were dabigatran 150 mg twice daily or rivaroxaban 20 mg once daily. Patients were followed until they were de-enrolled from Medicare, stopped the NOAC for ≥ 3 days, changed the NOAC, died, had a study outcome, or the study period ended.
Outcomes followed were thromboembolic stroke, intracranial hemorrhage, and major extracranial bleed (including major gastrointestinal bleed). Propensity score based patient-specific stabilized weighting was used to control for covariate imbalances and weighted Kaplan-Meier plots to characterize the risk of outcome over time.
There was a total of 52 240 new starts of dabigatran and 66 651 new starts of rivaroxaban during the study period. Rivaroxaban was associated with a non-significant decrease in thromboembolic stroke (HR 0.81; 95%CI 0.65-1.01; p = 0.07), yet statistically significant increases in intracranial hemorrhage (HR 1.65; 95%CI 1.20-2.26; p = 0.002) and extracranial bleeds (HR 1.48; 95%CI 1.32-1.67; p < 0.001). Specifically, for major gastrointestinal bleed, the risk for rivaroxaban as compared to dabigatran was HR 1.40; 95%CI 1.23-1.59; p < 0.001. There was also a non-significant increase in mortality associated with rivaroxaban (HR 1.15; 95%CI 1.00-1.32; p = 0.051).
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