Dr. Seeger: What is the background for this study? What are the main findings?
Response: This study is part of an ongoing research program initiated in 2013 to assess prescribing patterns and real-world safety and effectiveness of oral anticoagulants, including dabigatran, for the reduction of stroke risk. The study program is expected to run through the end of 2016. Boehringer Ingelheim and Brigham and Women’s Hospital are aiming to gather data from more than 100,000 U.S. NVAF patients.
Using a sequential matched cohort design, the safety and effectiveness of dabigatran compared to warfarin among patients with non-valvular atrial fibrillation (NVAF) receiving these medications in routine care settings can be assessed periodically. The interim findings at this stage come from 38,378 non-valvular atrial fibrillation patients in two health insurance databases, MarketScan (31,058 patients) and UnitedHealth (7,320 patients). The primary analysis follows patients from start of therapy until a switch or discontinuation of the anticoagulant, an outcome event, or disenrollment. The average follow-up was five months for patients in the dabigatran group and four months for those taking warfarin. The primary outcomes measured in the analysis are stroke and major hemorrhage.
Interim findings from the combined databases showed a 25 percent reduction in the rate of major hemorrhage (hazard ratio [HR] 0.75, 95 percent confidence interval [CI] 0.65-0.87, 354 vs. 395 events) and a 23 percent reduction in strokes (HR 0.77, CI 0.54-1.09, 62 vs 69 events) for dabigatran compared to warfarin among these patients with NVAF. The database-specific results indicate a reduction in the rate of major hemorrhage with dabigatran (MarketScan: HR 0.78, CI 0.67- 0.91; UnitedHealth: HR 0.56, CI 0.36-0.86). In the larger MarketScan database, dabigatran reduced the stroke rate by 36 percent (HR 0.64, CI 0.44-0.95), while in the smaller UnitedHealth database, stroke rates were not different between the two anticoagulants, as there were only 26 strokes in total which led to wide confidence intervals (HR=1.62, CI 0.72-3.66).
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Seeger: Our interim data are encouraging with respect to the safety and effectiveness of dabigatran in this analysis of data from routine care settings since they are consistent with what was seen in the pivotal clinical trial, RE-LY®. Results highlight the limitations of small event numbers, e.g. stroke in anticoagulated patients, in early stages of post-marketing monitoring programs making chance a likely explanation for variations in point estimates between databases. Assessments of effectiveness beyond the first six months of therapy are limited by the short average follow-up.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Seeger: It is important to quantify the comparative safety and effectiveness of new drugs in routine care. We will continue to gather data through this long-term study program and look forward to sharing future follow-up analyses.
Citation: AHA14 abstract :
Seeger J, Bartels D, Huybrechts K et al. Safety and Effectiveness of Dabigatran Relative to Warfarin in Routine Care. Abstract No. 16227. Presented at: American Heart Association Scientific Sessions 2014. November 15-19, 2014, Chicago, Illinois.