NEW ORLEANS—The direct thrombin inhibitor dabigatran etexilate is a safe, effective anticoagulant that, unlike warfarin, does not require routine monitoring or dose adjustments, according a presentation at 2009 ASH Annual Meeting.
In the past 20 years, research has intensified to find a competitor to warfarin, said Sam Schulman, MD, of McMaster University in Ontario, Canada.
Ximelagatran had been approved in Europe and other countries for the prevention of venous thromboembolis (VTE), but it was withdrawn in 2006 due to the induction of liver problems.
Dabigatran, like ximelagatran, slows down thrombin, Dr Schulman said.
“Dabigatran is an oral drug with quick onset; it works within 1 to 2 hours,” he explained. “There are few interactions of dabigatran with other drugs, and there is no metabolism in the liver. It can be delivered in a fixed dose that does not require monitoring and should make life easier for patients.”
The drug has been approved in Europe and Canada for the prevention of VTE in orthopedic surgery patients and has been studied in atrial fibrillation.
Dr Schulman led the RE-COVER trial, a randomized, double-blind, trial comparing dabigatran and warfarin in 2539 patients with acute VTE.
Patients were first treated with low-molecular-weight or unfractionated heparin for 5 to 11 days. They then received dabigatran at 150 mg twice daily in a fixed dose (n=1274) or warfarin dose-adjusted to an International Normalized Ratio of 2.0 and 3.0 (n=1265). Patients received treatment for 6 months.
The patient characteristics were well-balanced between the two groups, Dr Shulman said. The patients had a mean age of 55 years and were predominantly Caucasian. There were slightly more men than women. One quarter of the patients had had a previous VTE.
Both groups showed similar treatment improvements. At 6 months, 30 patients (2.4%) taking dabigatran and 27 patients (2.1%) taking warfarin developed new blood clots.
“This is well below the predetermined margin for non-inferiority of dabigatran,” Dr Shulman said.
Subgroup analyses showed dabigatran was just as effective as warfarin.
Safety data showed that 20 patients (1.6%) on dabigatran and 24 patients (1.9%) on warfarin developed major bleeding. There was 1 fatal bleeding episode in each group. In the dabigatran arm, 207 patients experienced any bleeding, compared to 280 patients in the warfarin arm.
Dabigatran also led to a 37% reduction in the risk of clinically relevant bleeding, Dr Shulman said.
There was no difference between the two groups in other major side effects, including myocardial infarction and abnormal liver function tests.
“Dabigatran shows comparable efficacy to warfarin,” Dr Shulman said. “It is as safe as warfarin in terms of bleeding rates. Dabigatran provides a more convenient, fixed-dose treatment for acute VTE with the potential to replace warfarin.”
He added that parallel studies in acute VTE are planned to test dabigatran in a population that includes more Asians. Two studies of extended therapy are planned, one to compare dabigatran to placebo and the other to compare it to warfarin.
