Bleeding Events among New Starters and Switchers to Dabigatran Compared with Warfarin: an Observational Study among Patients with Atrial Fibrillation

BACKGROUND: The bleeding risk among patients withatrial fibrillation is higher early after initiating therapy with vitamin K antagonists (VKA). Evidence is limited on how prior VKA-experience affects bleeding risk when initiating novel oral anticoagulant therapy.Weinvestigated this among patientswith atrial fibrillationinitiating dabigatran therapy.

METHODS AND RESULTS: Using nationwide Danish prescription and patient registries, we identified 11,315 first-time dabigatran users with atrial fibrillation. Warfarin controls were matched in a 2:1 ratioaccording to VKA-experience status. Average follow-up time was 13 months. Across the six combinations of treatment (dabigatran 110mg, dabigatran 150mg, and warfarin) and VKA-experience status (naive or experienced), VKA-naïve warfarin initiatorshad the highest rate of any bleeding event.Cox regressions adjusted for baseline characteristics showed reductions relative to this group ranging from 19% for VKA-experienceddabigatran 110mgusers (hazard ratio [HR]: 0.81,95% confidence interval [CI]: 0.66to 1.00) to 41% for VKA-experienced dabigatran 150mg users (HR: 0.59,95% CI: 0.46to 0.75). Among switchers todabigatran from warfarin, when comparing against warfarin-persisting users, the rateof any bleeding were non-significantly decreased for switchers to dabigatran 150mg (HR: 0.80, 95% CI: 0.62to 1.03) but not for switchers to dabigatran 110mg (HR: 1.12, 95% CI: 0.90to 1.41). Results for major bleeding were similar. Crude rates of fatal, intracranial, and gastrointestinal bleeding were low.

CONCLUSIONS: VKA-naïve warfarin initiators had the highest overall bleeding rate. We foundno evidence of marked excess of overallbleeding events whencomparing dabigatran with warfarin users, irrespective of prior VKA-experience.