Dabigatran Linked to Excess Bleeding Risk

The risk of bleeding complications is increased for patients with atrial fibrillation taking dabigatran compared with warfarin—and patients with chronic kidney disease are among the highest-risk subgroups, according to a report in JAMA Internal Medicine.

The retrospective cohort study used pharmacy and medical claims data for a random 5 percent sample of Medicare beneficiaries in 2010 to 2011. Two groups of patients who started anticoagulant treatment within 60 days after diagnosis of atrial fibrillation were identified: 1302 receiving dabigatran and 8102 receiving warfarin. Episodes of major and minor bleeding by site were compared between groups, with propensity score weighting to account for differences in patient characteristics.

Patients starting treatment with dabigatran had higher bleeding rates than did those starting warfarin: hazard ratio (HR) 1.30 for any bleeding event and 1.58 for major bleeding. The adjusted rates of major bleeding were 9.0 percent with dabigatran versus 5.9 percent with warfarin. The risk of gastrointestinal bleeding was also higher with dabigatran: HR 1.85.

The rates of most types of bleeding complications were higher with dabigatran, including hematuria (HR 1.41), vaginal bleeding (HR 2.27), hemarthrosis (HR 2.78), and hemoptysis (HR 1.49). The exception was intracranial hemorrhage: HR 0.32 with dabigatran.

The excess bleeding risk remained significant in defined high-risk subgroups. The rates of major bleeding with dabigatran were particularly high for African American patients (HR 2.12) and for patients with chronic kidney disease (HR 2.07).

Soon after the approval of dabigatran, there were reports of severe bleeding events, particularly among elderly patients and those with renal impairment. Subsequent studies of this risk have yielded conflicting results.

This large analysis of Medicare beneficiaries with atrial fibrillation supports concerns about higher bleeding risk with dabigatran, compared with warfarin. The authors urge caution in prescribing dabigatran, especially to African Americans and patients with chronic kidney disease renal impairment. They also highlight the elevated risk of gastrointestinal bleeding across all patient subgroups [Hernandez I, et al. Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med doi:10.1001/jamainternmed.2014.53980].