ATLANTA—Patients treated with dabigatran who experienced major bleeding had a better prognosis than those taking warfarin, including a shorter stay in intensive care, investigators reported during the 54th American Society of Hematology Annual Meeting and Exposition.
“Dabigatran’s safety profile is more favorable than that of warfarin, even in the presence of effective reversal agents for warfarin,” said Ammar Majeed, MD, Hematology Center, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden. “The management of severe bleeding on dabigatran can be further improved by access to a specific antidote, which is in development,” he added.
Dr. Majeed and colleagues reviewed management of major bleeding events and compared use of blood products, length of stay in intensive care and in the hospital, and mortality after major bleeds between the two treatment groups.
Two independent investigators reviewed all reports on 1,121 major bleeds in five phase 3 long-term trials of dabigatran in 27,419 patients with atrial fibrillation followed for 6 to 36 months, including acute treatment and secondary prevention of venous thromboembolism. Only cases of centrally adjudicated major bleeding within 3 days of the last dose were included in the bleeding case narrative analysis.
Among the phase 3 trials, 627 patients in the dabigatran arm had major bleeding vs 407 in the warfarin age. Patients in the dabigatran arm were older, 75.3 years vs 71.8 years in the warfarin arm (P<0.0001), and two thirds of the patients were male (64.4% vs 65.9%).
“Patients with major bleeds on dabigatran were older, had lower creatinine clearance, and had more frequent use of aspirin or nonsteroidal antiinflammatory agents than those on warfarin,” Dr. Majeed said.
In the RE-LY study, 439 of 741 patients (59.2%) had major bleeds transfused with red cells vs 210 of 421 patients (49.9%) on warfarin (P=0.002). However, those on warfarin required more fresh frozen plasma transfusions (30.2% vs 19.8%; P<0.001) and more vitamin K for bleeding management (27.3% vs 9.4%; P<0.001) than those on dabigatran.
Mean length of stay in intensive care was 2.7 days for those on warfarin vs 1.0 days for those on dabigatran (P=0.01). A total of 15% of patients on warfarin had bleeds requiring surgery vs 12.2% with dabigatran (P=0.017). Recombinant factor VIIa was used for eight patients treated with dabigatran and three with warfarin (P=0.53).
Outcomes based on event reports from the five phase 3 trials found a reduced risk for death with dabigatran vs warfarin during 30 days from bleeding (P=0.052). Mortality did not differ significantly based on age, creatinine clearance, or use of aspirin.
“Despite the unavailability of a specific antidote against dabigatran, the overall resources required to manage bleeding are not greater,” Dr. Majeed concluded. “More frequent transfusion with red cells is counterbalanced by shorter stay in the intensive care unit and less frequent transfusion of plasma.”