Title: 262 Initial Experience With Idarucizumab in Dabigatran-Treated Patients Presenting With Acute Traumatic Injuries: Interim Results From the RE-VERSE AD Study
Abstract: Dabigatran, an oral thrombin inhibitor, is widely used in the US for stroke prevention in atrial fibrillation and for treatment and secondary prevention of venous thromboembolism. In clinical trials, dabigatran is associated with fewer and less severe bleeding events than warfarin. Clinical trial results have subsequently been confirmed in large real-world studies. Still, bleeding on dabigatran therapy may occur. Although its activity can be countered by established, nonspecific treatment algorithms, a reversal agent for dabigatran would be helpful, especially in the emergency department (ED) management of acute trauma. Idarucizumab, a humanized Fab fragment directed specifically against dabigatran, rapidly reverses the anticoagulant effects of dabigatran in healthy volunteers and attenuates bleeding in animal injury models. Therefore, idarucizumab has the potential to simplify management of dabigatran-treated patients who present after serious trauma. In the ongoing phase III RE-VERSE AD study (NCT02104947), dabigatran-treated patients with uncontrolled bleeding or who require emergency surgery are given 5 g of intravenous idarucizumab. The primary endpoint is the maximum reversal of the anticoagulant effect of dabigatran, based on central laboratory determination of the dilute thrombin time (dTT) or ecarin clotting time. Secondary endpoints include clinical outcomes, extent and duration of bleeding, local aPTT measures, use of other hemostatic therapies, blood product transfusions, and hemostasis at surgery (for patients who require operative management). Of the first 90 patients given idarucizumab in RE-VERSE AD, 9 dabigatran-treated patients had active, uncontrolled bleeding as a result of acute trauma, and 9 others were not bleeding but required emergency surgery. All 18 injured patients received the reversal agent in open-label fashion, based on the treating clinician’s impression that reversal was warranted. The injuries were: 9 fractures (3 femoral neck, 2 femur, 1 ankle, 1 wrist, 1 hip, 1 femur and spine) all requiring emergency surgery, 6 head traumas (3 subdural, 2 subarachnoid, 1 subarachnoid and intracerebral bleeds), and 3 blunt traumas leading to major soft tissue bleeding (1 retroperitoneal, 2 intramuscular). Mean age (±SD) of the 18 patients was 76.53 ± 8.85 y. As measured by dTT, 5g idarucizumab resulted in complete reversal of dabigatran-induced anticoagulation in each case by the end of the infusion. Of the 9 fracture cases, hemostasis during surgery was reported to be normal in 7 cases, mildly abnormal in 1 case, and, due to polytrauma, not directly assessable in 1 case. Of the 9 cases with bleeding related to trauma, bleeding cessation was reported in 4 cases, reduction was reported in 2 cases, and bleeding status was not assessable in 3 cases. Of the 6 head trauma patients, the three subdural hematomas were additionally managed operatively. All 18 patients survived to hospital discharge. Idarucizumab is a rapid acting, specific reversal agent for dabigatran. Preliminary results from the RE-VERSE AD study suggest that idarucizumab has the potential to streamline and improve the management of dabigatran-treated injured patients who require rapid drug reversal in the ED.