Cancer patients are at high risk for venous thromboembolism (VTE), a leading cause of death in patients with cancer. Fixed-dose dabigatran may be a replacement for warfarin in the treatment of VTE, according to results of the large Phase III RE-COVER trial.
— Cancer patients are at high risk for venous thromboembolism (VTE), a leading cause of death in patients with cancer. Fixed-dose dabigatran may be a replacement for warfarin in the treatment of VTE, according to results of the large Phase III RE-COVER trial. The study was published online to coincide with its presentation at the 51st Annual Meeting of the American Society of Hematology (N Engl J Med, Dec. 6, 2009).
RE-COVER found that fixed-dose dabigatran significantly reduced major or clinically relevant bleeding. In addition, it was as effective as dose-adjusted warfarin in preventing recurrent symptomatic VTE and VTE-related death in patients treated for acute VTE.
The new oral direct thrombin inhibitor has several important advantages over warfarin, the current standard for anticoagulation. Dabigatran does not require frequent monitoring and dosing adjustments to keep patients in a therapeutic range. Unlike warfarin, dabigatran does not interact with food and other drugs, so no dietary adjustments are needed.
“Dabigatran is a potential replacement for warfarin, explained Sam Schulman, MD, Professor at McMaster University in Hamilton, Ontario, Canada.
The global, prospective, double-blind, double-dummy study randomized 2539 patients 1:1 to 6 months of treatment with a fixed 150-mg dose of dabigatran twice daily or warfarin (International Normalized Ratio, 2.0-3.0). Mean age of patients was 55 years, and ~ 42% were female, ~69% had deep vein thrombosis (DVT) as the index event, ~22% had pulmonary embolism (PE) only, and ~10% had DVT and PE. One-quarter of patients had a history of previous VTE.
The cumulative risk of recurrent or fatal VTE after 6 months of treatment was similar for both groups. Recurrent VTE occurred in 30 patients (2.4%) in the dabigatran-treated group and 27 patients (2.1%) in the warfarin group. This difference in risks of 0.4 percentage points established that dabigatran was non-inferior to warfarin.
Dabigatran reduced the risk of any bleeding event by 29% compared with warfarin (P = .0002). Any bleeding event occurred in 205 patients (16.1%) in the dabigatran group and 277 (21.9%) assigned to warfarin. Major bleeding occurred in 20 patients (1.6%) in the dabigatran group and in 24 (1.9%) in the warfarin group. Major or clinically relevant bleeds were reduced by 37% in the dabigatran group (5.6% versus 8.8%, respectively, P = .002).
Deaths, acute coronary syndromes, and abnormal liver function tests were similar in the two arms of the study. Discontinuations due to adverse events occurred in 9% of those assigned to dabigatran and in 6.8% of those assigned to warfarin (P = .05).
“There is no signal of danger in the liver with dabigatran. Ximelegatran, a predecessor, was killed by elevations in ALTs and bilirubin,” Dr Schulman said. ASH Abstract 1.