Sequential Monitoring of the Comparative Effectiveness and Safety of Dabigatran in Routine Care

Background The increasing availability of electronic healthcare data enables ongoing monitoring of the effectiveness and safety of newly marketed medications. We sought to demonstrate a 5-year prospective monitoring system of dabigatran for stroke prevention that may expedite discovery and allow ongoing evidence development. Methods and Results Between 2011 and 2015, we conducted 9 sequential analyses of dabigatran versus warfarin users in a sequential cohort design in 2 US claims databases. Analyses 4 through 9 were prespecified, and analyses 1 through 3 were added subsequently using the same methodology. New users of anticoagulants with nonvalvular atrial fibrillation were followed until a study outcome of hospitalization for stroke (hemorrhagic and ischemic) or hospitalization for major hemorrhage (intracranial and extracranial). Hazard ratios and 95% CIs were estimated after 1:1 propensity score matching. Sequential analyses 1 through 3 on stroke prevention using data through June 2012 were limited by few events leading to wide CIs. As data accumulated the effect estimate in analysis 4 visually stabilized at a 25% risk reduction with increasingly narrower CIs (-46% to +9% in December 2012 and -42% to -2% in September 2015). Improved data-adaptive confounding adjustment with high-dimensional propensity score reached a stable state already at analysis 3 and was slightly closer to the randomized clinical trial finding (-39%). The risk of major hemorrhage was 28% lower in dabigatran initiators (-35% to -20%) a finding that was stable throughout analyses 2 to 9. Conclusions Prospectively monitoring the effectiveness and safety of dabigatran for stroke prevention allowed for early insights with increasing precision over time.