Boehringer Ingelheim has announced results from two new post-hoc sub-analyses comparing the clinical management and outcomes of patients who experienced major bleeding while treated with dabigatran or warfarin.
These findings from the RE-LY trial and four other phase III trials report outcomes after a major bleed on dabigatran, despite the lack of a specific reversal agent, may be better than after a warfarin-associated bleed. The sub-analyses also indicate that the overall medical resources used to manage bleeding were not greater with dabigatran. These data were presented on 8 December at the 54th Annual Meeting of the American Society of Hematology in Atlanta, USA.
“Bleeding, especially major bleeding, is a well-recognised concern with all blood thinners. The sub-analyses report that major bleeding outcomes with dabigatran, using standard clinical support measures, appeared to be better than warfarin and required no greater use of medical resources,” said Sam Schulman, professor, Department of Medicine, McMaster University, Ontario, Canada.
The data consist of two retrospective sub-analyses that reviewed the use of resources and hospital length of stay after major bleeds in patients treated with dabigatran or warfarin.
- A sub-analysis of the RE-LY trial examined patients with non-valvular atrial fibrillation (NVAF) treated with dabigatran 110mg and 150mg.
- A pooled sub-analysis assessed reports of 1,034 major bleeds (627 dabigatran, 407 warfarin) in five phase III studies, including the RE-LY trial, in patients with NVAF and four other phase III dabigatran trials in patients with acute treatment and secondary prevention of venous thromboembolism (VTE). This analysis is based on a case narrative analysis and included only centrally adjudicated (meaning confirmed by an independent team or group) major bleeding events within three days of the last dose.
In the sub-analysis of the RE-LY study alone, the rate of major bleeds requiring surgery was lower for patients on dabigatran than warfarin (12.1% and 15%, respectively). While dabigatran and warfarin patients were hospitalised at the same rates and length of stay was the same, time spent in the intensive care unit (ICU) and coronary care unit (CCU) was less for patients on dabigatran than on warfarin (1.6 nights and 2.7 nights, respectively).
Management of bleeding events for dabigatran or warfarin was based on current standards of clinical care, including: blood transfusion, fresh frozen plasma, vitamin K, prothrombin complex concentrate and recombinant factor VIIa. In the RE-LY sub-analysis alone, patients on dabigatran were more frequently treated with blood transfusions than those on warfarin (59.2 percent and 49.9 percent, respectively). Patients on dabigatran were less frequently treated with fresh frozen plasma than those on warfarin (19.8% and 30.2%, respectively).
More patients in the dabigatran group were older than the warfarin group (mean age of 75.3 and 71.8, respectively), had lower median creatinine clearance (53 mL/min and 62 mL/min, respectively) and were using aspirin (30.9% and 24.6%, respectively) or non-steroidal anti-inflammatory drugs (12.9% and 8.4%, respectively).