While approved therapeutic agents such as dabigatran and rivaroxaban have proven to be a welcome alternative to the difficult-to-manage warfarin, a letter to the editor published Nov. 24 in the New England Journal of Medicine questioned the overarching safety and efficacy of dabigatran and urged the FDA to conduct more pragmatic trials.
In the correspondence, Bryan A. Cotton, MD, MPH, of the Center for Translational Injury Research in Houston, and colleagues wrote that trauma accounts for 40,000 deaths per year in patients over the age of 65 and that hospitals are seeing more and more cases of hemorrhagic complications and head injuries.
“Although the preinjury use of warfarin is increasing and is associated with a considerable increase in morbidity and mortality, these complications can be dramatically reduced with methods that rapidly reverse the anticoagulant effect,” Cotton and colleagues wrote. “Moreover, numerous options are available to achieve warfarin reversal (e.g., vitamin K, plasma, factor VIIa and factor concentrates). Warfarin reversal can also be easily monitored with readily available laboratory and point-of-care tests.”
The authors noted three concerns with dabigatran (Pradaxa, Boehringer Ingelheim): there is no readily available means for assessing the degree of anticoagulation with the drug, there is no readily available reversal strategy and life-threatening bleeds can occur after an injury in patients administered the drug.
Cotton et al noted that the fact that there is no readily available method to determine the degree of anticoagulation on dabigatran remains a problem. “Moreover, the irreversible coagulopathy of dabigatran is of great concern to trauma and emergency physicians,” the authors said.
Currently, emergency dialysis is the only reversible option for dabigatran.
“The ability to perform rapid dialysis in patients with bleeding whose condition is unstable or in those with large intracranial hemorrhages will present an incredible challenge, even at level 1 trauma centers,” the authors speculated.
According to the authors, severely injured patients treated with dabigatran at their facility all had poor outcomes. While results of coagulation studies were normal, values obtained on rapid thromboelastography (rTEG) at the time of admissions “were grossly abnormal.
“As dabigatran and other similar therapeutic agents move into the marketplace, we urge the FDA to consider the generalizability of study findings and to support more pragmatic trials,” Cotton et al summed.
Additionally, they urged that hemorrhagic complications and mortality resulting from trauma be part of surveillance of the newly approved anticoagulants now on the market.