Fixed-dose dabigatran as safe, effective as warfarin

A fixed-dose of dabigatran, a new oral thrombin inhibitor, for the treatment of patients with acute venous thromboembolism had similar safety and efficacy to warfarin, according to investigators of a recently presented study.

“We are excited by these findings and feel that they will change the standard of care for venous thromboembolism (VTE), which affects a large number of our patients,” Sam Schulman, MD, professor of medicine at McMaster Clinic and Hamilton General Hospital in Ontario, Canada, said in a press release.

“This [study’s findings demonstrated] that dabigatran is a safe and effective anticoagulant that does not require the routine monitoring or dose adjustments that are necessary with warfarin. In other words, patients can receive the same results in a more convenient manner,” he noted in the release.

Dabigatran is not approved for use in the United States.

Schulman presented the findings of the trial, which were published simultaneously in The New England Journal of Medicine, during a press conference at the American Society of Hematology’s (ASH) 51st Annual Meeting.

Researchers randomly assigned 1,274 patients to a fixed dose of dabigatran [Pradax, Pradaxa; Boehringer Ingelheim] 150 mg twice daily and 1,265 patients to warfarin once daily in doses adjusted to an International Normalized Ratio of 2.0 to 3.0. International Normalized Ratio was performed an average of every 11 days, according to researchers.

After 6 months of treatment, 2.4% of patients assigned to dabigatran and 2.1% of patients assigned to warfarin experienced recurrent VTE. Safety was comparable between the two drugs. Two hundred and five patients in the dabigatran group had bleeding, including 20 patients with major bleeding, and 277 patients in the warfarin group had bleeding, including 24 patients with major bleeding.

Adverse effects included death, acute coronary syndromes and abnormalities in liver function tests; however, they were infrequent in both treatment groups.

“We will continue conducting three more ongoing studies: one is a parallel study with essentially the same design but with a higher proportion of the Asian population to demonstrate efficacy in other ethnicities, and two studies will assess extended treatment. We will have the results of these studies within the next year or two,” Schulman said during at an ASH press conference.

“A number of new oral anticoagulants are in development. Two of them, rivaroxaban and dabigatran, are approved in a number of countries, but not the United States, for venous thromboembolism prevention after knee and hip replacement surgery,” Stephan Moll, MD, Associate Professor, Division of Hematology-Oncology, University of North Carolina School of Medicine, Chapel Hill, told HemOnc Today, a sister publication to ORTHOSuperSite.com.

“The large 2,539-patient phase-3 trial on ‘Dabigatran in the Treatment of Venous Thromboembolism’ presented in the plenary session showed that the antithrombin drug, given twice daily in a fixed dose and without anticoagulant blood monitoring, was equally effective and safe in preventing venous thromboembolism recurrence as warfarin. Liver function abnormalities were infrequent and occurred with similar frequency in both treatment groups.”

Moll said the study is noteworthy because dabigatran is the first of the new oral anticoagulant VTE treatment trials that has been completed. “It is a significant step forward on our path to get a warfarin alternative into clinical practice and make anticoagulant therapy easier for patients who suffer a venous thromboembolism,” Moll said.

For more information:
Schulman S. Dabigatran in the Treatment of Venous Thromboembolism. Paper #1. Presented at: 51st ASH Annual Meeting and Exposition, Dec. 4-8, 2009, New Orleans.
The study was funded by Boehringer Ingelheim.