Recent studies published in the New England Journal of Medicine suggest that two new anticoagulants may be effective and safe for the treatment of venous thromboembolism. Patients with venous thromboembolism often require extended therapy to prevent recurrence. While warfarin is typically used and over 90% effective, it is burdensome and comes with a significant risk of major bleeding. Dabigatran and apixaban are two new medications which can be administered in fixed doses and do not require laboratory monitoring.
Dr. Sam Schulman conducted two trials to compare dabigatran to warfarin and to a placebo, among patients who had completed at least 3 months of anticoagulation therapy.
Here is Dr. Schulman:
“We now have new anticoagulants which are much more convenient because you don’t need routine coagulation monitoring and adjustment of the dose but the question is if they also reduce the bleeding compared to warfarin. So we performed these studies to compare dabigatran, an oral thrombin inhibitor, versus the standard – warfarin, but also versus placebo.”
The trials showed that dabigatran was non-inferior to warfarin in preventing recurrent venous thromboembolism. In addition, patients receiving dabigatran had a 46% lower risk of major or clinically relevant bleeding. Compared to placebo, dabigatran was 92% less likely to result in recurrent venous thromboembolism.
A third trial compared apixaban to placebo among over 2400 patients with venous thromboembolism, who had completed 6 to 12 months of anticoagulation therapy. Apixaban is an oral factor Xa inhibitor. The drug was associated with a reduced risk of symptomatic recurrence and death, but did not increase risk of major bleeding.
In an accompanying editorial, Dr. Jean Connors discussed the trial results.
“The new oral anticoagulants are advances in anticoagulant therapy that will make it significantly easier to use anticoagulation for extended treatment of venous thromboembolism. They may ultimately prove to be safer than warfarin due to lower bleeding rates but a current problem with their use is the lack of good reversal strategies for patients who do experience bleeding or excessive drug levels. A variety of blood products and factor concentrates have been used in controlled experiments to reverse the anticoagulation effects of these drugs with variable results.”
Dabigratan and apixaban are not currently approved for either short-term or extended treatment of venous thromboembolism. Further research is needed to identify patients who would benefit most by these new drugs.
We’ll be back on April 15th with another edition of Transfusion News. Thanks for joining us.
2. Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013;368: 709-18