Reversal of Dabigatran Effects with Idarucizumab in Patients Requiring Urgent Procedures: Subanalysis of the RE-VERSE AD Study
The effect of idarucizumab as a reversal agent in patients treated with dabigatran in situations requiring urgent surgery or other invasive procedures was evaluated in a subanalysis from the RE-VERSE AD study published in 2021.
Urgent Surgical Procedures in Patients Treated with Dabigatran
Patients who need to undergo urgent surgical procedures have a high risk of bleeding. This risk is conditioned by several factors, including tissue damage, dilutional coagulopathy, or consumption of clotting factors related to inflammation. This risk is further amplified by anticoagulant therapy.
Direct oral anticoagulants (DOACs) have brought several benefits, particularly comfortable and highly effective treatment. However, their effect must be reversed in the case of an acute surgical procedure.
Dabigatran is the only DOAC for which an antibody is available that can rapidly and effectively neutralize the anticoagulant effect. The antibody idarucizumab is a humanized Fab fragment that binds to dabigatran with high affinity.
The RE-VERSE AD study documented a rapid and complete response to idarucizumab, when administered to patients due to life-threatening bleeding or urgent surgery. A subanalysis published in 2021 further evaluated a group of patients from the RE-VERSE AD study who required urgent surgery or another intervention.
Evaluated Population
A total of 202 patients who required an urgent invasive procedure (within 8 hours) and needed to achieve normal hemostasis were evaluated. They were given a total dose of 5 g of idarucizumab before the procedure in two bolus infusions of 2.5 g each.
This included 49 abdominal surgeries (e.g., bowel perforation, cholecystitis, incarcerated hernia), 45 orthopedic interventions (mostly trauma from falls), 34 vascular procedures (ruptured aneurysms or aortic dissection, heart transplants, etc.), 8 neurological and 4 genitourinary procedures. Additionally, 29 cases of catheter insertion, 20 cases of drain placement, and 8 diagnostic procedures were included.
The median time from the last dose of dabigatran (as reported by the patient) to the administration of idarucizumab was 11−25 hours, and the median dabigatran levels on study entry were 41−77 ng/ml. At study entry, 90.1% of patients had prolonged aPTT, dTT, or ECT.
Results
Efficacy
Complete reversal of the effects of dabigatran was achieved in all patients within minutes, and normal hemostasis was attained in more than 91% of patients. The median time from the first administration of idarucizumab to surgery was less than 2 hours across all groups, except for neurosurgical procedures, where the median time was 3.3 hours.
Safety
Thromboembolic events were observed in 10 (5%) patients within 30 days after the administration of idarucizumab, with 5 of these patients already resuming anticoagulant medication before the event. The overall mortality rate within 30 days of idarucizumab administration was 12.6%. No serious safety adverse events related to the administration of the reversal antibody were observed.
Conclusion
This analysis demonstrated that idarucizumab significantly facilitates the management of urgent surgical procedures or invasive interventions in patients requiring anticoagulant therapy with dabigatran. Idarucizumab provides a very rapid and effective reversal of the anticoagulant effect of the otherwise highly potent DOAC, thus enabling safer execution of essential invasive procedures.
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Source: Levy J. H., van Ryn J., Sellke F. W. et al. Dabigatran reversal with idarucizumab in patients requiring urgent surgery. A subanalysis of the RE-VERSE AD Study. Ann Surg 2021; 274: e204–e211,
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