Photo by Piotr Bodzek
Team performing surgery
BERLIN—Final results from the RE-VERSE AD trial suggest idarucizumab can reverse the anticoagulant effect of dabigatran etexilate mesylate in emergency situations.
Patients who required dabigatran reversal because they needed urgent surgery were able to have their procedure a median of 1.6 hours from idarucizumab administration.
In patients who required dabigatran reversal due to uncontrollable bleeding, the median time to bleeding cessation was 2.5 hours. However, the time to bleeding cessation could not be assessed in all patients.
“RE-VERSE AD has shown that idarucizumab reverses the anticoagulant effect of dabigatran within minutes so that treating physicians can fully focus on dealing with the emergency at hand,” said study investigator Charles Pollack, MD, of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania.
“Prior to idarucizumab, there was no rapid, reliable, and effective method for reversing dabigatran and other orally administered blood thinners, which otherwise may take at least 12 to 24 hours to clear from the body.”
The rate of thrombotic events in RE-VERSE AD was low (6% to 7%), and researchers said there were no serious adverse safety signals related to idarucizumab.
These results were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress and published in NEJM. The research was funded by Boehringer Ingelheim Pharmaceuticals.
The phase 3 trial enrolled 503 patients who required dabigatran reversal. They were divided into 2 groups.
Group A included 301 patients with uncontrolled or life-threatening bleeding complications (eg, intracranial hemorrhage or severe trauma after a car accident).
Group B included 202 patients requiring an invasive procedure or an emergency surgery or intervention (eg, surgery for an open fracture after a fall).
Results
The study’s primary endpoint was the degree of reversal of the anticoagulant effect of dabigatran achieved by idarucizumab within 4 hours. This was measured by diluted thrombin time or ecarin clotting time.
The median maximum percentage of dabigatran reversal was 100%. Dabigatran reversal occurred independently of patients’ age, sex, renal function, and dabigatran concentration at baseline.
Group A
Roughly 68% of evaluable patients in Group A (134/203) had confirmed bleeding cessation within 24 hours of idarucizumab administration.
Bleeding cessation was not confirmed in 67 patients, bleeding stopped before treatment in 2 patients, and the time to bleeding cessation could not be assessed in the 98 patients with intracranial bleeding.
Among the 134 patients in who had confirmed bleeding cessation, the median time to hemostasis after idarucizumab administration was 2.5 hours.
Sixty-seven percent (n=201) of patients in Group A received hemostatic treatment, 62% (n=185) received whole blood/blood components, 7% (n=20) received plasma derivatives, and 23% (n=69) received volume expanders, pro-hemostatic agents, albumin, and other treatments.
At 90 days, thrombotic events had occurred in 6.3% of the patients in Group A, and the mortality rate was 18.8%.
Group B
For patients in Group B, their required procedures began a median of 1.6 hours from idarucizumab administration.
Hemostasis during the procedure was described as normal for 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%.
Thirty-nine percent (n=79) of patients in Group B received hemostatic treatment, 26% (n=53) received whole blood/blood components, 4% (n=8) received plasma derivatives, and 21% (n=42) received volume expanders, pro-hemostatic agents, albumin, and other treatments.
At 90 days, thrombotic events had occurred in 7.4% of patients in Group B, and the mortality rate was 18.9%.
