Idarucizumab for the treatment of hemorrhage and dabigatran reversal in patients requiring urgent surgery or procedures

Abstract

Idarucizumab is a specific antagonist for dabigatran etexilate (DE). The recent market authorization of idarucizumab in Europe and the USA may reassure prescribers of DE, as it can increase the safety of the emergency management of patients taking this anticoagulant. However, idarucizumab use should be limited to specific indications to avoid unnecessary risks to patients and costs to healthcare systems. Areas covered: The authors provide an overview of idarucizumab development and its pharmacokinetic and pharmacodynamic properties. The results of the clinical phase III trial RE-VERSE AD and a review of recent case reports of idarucizumab use in emergency contexts are also discussed. Expert opinion: Although idarucizumab has shown clear efficacy in reversing dabigatran-induced coagulopathy, its overall effects on patient outcome have not been proven. Information regarding the clinical context in which patients on DE are admitted for emergency treatment, and accurate laboratory tests of dabigatran plasma level during reversal may inform selection and help with the follow-up of patients who may benefit from idarucizumab. Idarucizumab should be integrated into protocol for the emergency management of patients on DE. Furthermore, the benefit of idarucizumab in specific indications such as acute ischemic stroke should be investigated.

Lessons learnt from local real‐life experience with idarucizumab for the reversal of dabigatran

“…Although TT/APTT is often used as a surrogate marker of dabigatran anticoagulant effect, we were unable to assess the association between renal impairment and definite dabigatran rebound due to an insufficient number of patients with dabigatran level measurements, despite the test’s availability at our central laboratory. Nevertheless, our results support the observation that patients with chronic or acute kidney injury are at an increased risk of experiencing a dabigatran rebound . The dabigatran rebound is thought to occur as a result of redistribution of unbound dabigatran from the extravascular to the intravascular compartment .…”

“…Nevertheless, our results support the observation that patients with chronic or acute kidney injury are at an increased risk of experiencing a dabigatran rebound. 10,11 The dabigatran rebound is thought to occur as a result of redistribution of unbound dabigatran from the extravascular to the intravascular compartment. 9 It is plausible that patients with renal failure and, consequently, higher plasma dabigatran levels have increased extravascular concentrations of dabigatran that is redistributed back into the intravascular compartment over time.…”

Performance of idarucizumab as antidote of dabigatran in daily clinical practice

“…6 Further insights on the clinical use of idarucizumab is only available from case reports and one small retrospective study demonstrating safe and effective idarucizumab administration in 31 patients with intracranial bleeding or ischaemic stroke prior to thrombolysis. 7,8 Even so, current international guidelines recommend idarucizumab usage for urgent dabigatran reversal in the presence of life-threatening bleeding or urgent surgery associated with high risk of bleeding. 9,10 It remains nonetheless to the clinician's discretion to decide in which clinical setting usage of idarucizumab is appropriate.…”

Systemic thrombolysis and endovascular thrombectomy in severe acute ischemic stroke after dabigatran reversal with idarucizumab

“…Indeed, studies with positive results have usually a greater chance of being written and published than those with negative results. Although idarucizumab has shown clear efficacy in reversing dabigatran‐induced coagulopathy, its overall effects on patient outcome have not been proven . This case report aims, with the clinical context and accurate laboratory tests of dabigatran plasma level during reversal, at a better selection and follow‐up of patients who may benefit from idarucizumab.…”