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Idarucizumab rapidly reverses anticoagulant effect of dabigatran, restores hemostasis
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Idarucizumab instantly and completely reversed the anticoagulant effect of dabigatran in patients requiring urgent procedures or with serious hematologic complications, according to interim results of a phase 3 study.
Few specific reversal agents exist for non-vitamin K oral anticoagulants, according to study background. Researchers developed idarucizumab (Boehringer Ingelheim) to reverse the anticoagulant effects of dabigatran (Pradaxa, Boehringer Ingelheim).
Charles V. Pollack, Jr., MD, chair of the department of emergency medicine at Pennsylvania Hospital and professor of emergency medicine at the Hospital of the University of Pennsylvania, and colleagues conducted the prospective, phase 3 RE-VERSE AD study to observe the safety and efficacy of idarucizumab in reversing the effects of dabigatran.
Pollack and colleagues divided the study into two arms: patients experiencing severe bleeding (group A) and patients who required an urgent procedure (group B).
The researchers assigned 5 mg IV idarucizumab to patients in both groups.
The maximum percentage reversal of the anticoagulant effect of dabigatran — evaluated with the dilute thrombin time or ecarin clotting time — within 4 hours of idarucizumab administration served as the primary endpoint. Restoration of hemostasis served as a secondary endpoint.
The interim analysis included data from 90 patients (group A, n = 51; group B, n = 39).
At baseline, 68 patients had an elevated dilute thrombin time and 81 had an elevated ecarin clotting time. The study achieved its primary endpoint, with 100% of these patients (95% CI, 100-100) reaching maximum percentage reversal following idarucizumab administration.
Idarucizumab normalized the dilute thrombin time in 98% of patients in group A and 93% in group B, as well as the ecarin clotting time in 89% of patients in group A and 88% of patients in group B. In most cases, researchers observed these effects within minutes of administration.
Concentrations of unbound dabigatran stayed below 20 ng/mL in 79% of patients after 24 hours.
The researchers assessed hemostasis in 35 patients in group A and 36 patients in group B. Among patients in group A, hemostasis restoration occurred at a median of 11.4 hours. Thirty-three patients in group B who underwent a procedure experienced normal intraoperative hemostasis, whereas two patients experienced mildly abnormal hemostasis and one patient experienced moderately abnormal hemostasis.
A total of 18 patients died (n = 9 for each arm). Ten patients died from vascular causes, with five deaths attributed to bleeding events. Eleven patients died within 96 hours of treatment; however, their deaths appeared to be related to their index event.
Five patients experienced thrombotic events, including deep vein thrombosis and pulmonary embolism in one patient within 72 hours of idarucizumab administration.
Twenty-one patients (group A, n = 13; group B, n = 8) experienced serious adverse events, including gastrointestinal hemorrhage (n = 2), postoperative wound infection, delirium, right ventricular failure and pulmonary edema (n = 1 for all).
The researchers identified the lack of a control group as a limitation of their study.
“The interim analysis from RE-VERSE AD is important for the healthcare professionals as it provides the first insights into the effect of a specific reversal agent to a non–vitamin K antagonist oral anticoagulant during real-word emergency situations,” Pollack said in a press release. “These data demonstrate that use of idarucizumab can help physicians focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients.” – by Cameron Kelsall
Disclosure: Boehringer Ingelheim provided funding for this study. Pollack reports personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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