JAMA study shows that Xarelto(rivaroxaban) from Bayer HealthCare and Janssen may cause more bleeds than Pradaxa (dabigatran) from Boehringer in non-valvular atrial fibrillation.

Patients with non-valvular atrial fibrillation treated with Xarelto (rivaroxaban) for stroke prevention were more likely to experience both intracranial haemorrhage and major extracranial bleeding than those treated with Pradaxa( dabigatran), a head-to-head trial published in JAMA Internal Medicine has shown.

Researchers analysed data on 118,891 patients with non-valvular atrial fibrillation, aged 65 or older, who had started treatment with dabigatran (150 mg, twice daily) or rivaroxaban (20 mg, once daily) between 4 November 2011 and 30 June 2014. A total of 52,240 patients treated with dabigatran and 66,651 patients treated with rivaroxaban contributed 15,524 and 20,199 person years of treatment,respectively. 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 (novel oral anticoagulant) 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 more than 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).

Conclusions and Relevance: Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in intracranial hemorrhage and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.

Comment: Johnson & Johnson, has responded that a true comparison of one NOAC to another can only be made through a randomized clinical trial.

See-"Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation- David J. Graham, MD, MPH; Marsha E. Reichman, PhD; Michael Wernecke, BA; et al -JAMA Intern Med. Published online October 3, 2016. doi:10.1001/jamainternmed.2016.5954 .