Idarucizumab for Dabigatran Reversal
Abstract
Background Specific reversal agents for non-vitamin K antagonist oral anticoagulants are lacking. Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran. Methods We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time. A key secondary end point was the restoration of hemostasis. Results This interim analysis included 90 patients who received idarucizumab (51 patients in group A and 39 in group B). Among 68 patients with an elevated dilute thrombin time and 81 with an elevated ecarin clotting time at baseline, the median maximum percentage reversal was 100% (95% confidence interval, 100 to 100). Idarucizumab normalized the test results in 88 to 98% of the patients, an effect that was evident within minutes. Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79% of the patients. Among 35 patients in group A who could be assessed, hemostasis, as determined by local investigators, was restored at a median of 11.4 hours. Among 36 patient…
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Idarucizumab is a clinically available humanized antibody fragment that binds dabigatran and rapidly and dose-dependently reverses its effects without over-correction or thrombin generation.
“Idarucizumab (approved in 2015 by the US Food and Drug Administration and the European Medicines Agency) is a clinically available humanized antibody fragment that binds dabigatran and rapidly and dose-dependently reverses the effects without over-correction or thrombin generation.475”
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- Authors
- Pollack, C. V., Reilly, P. A., Eikelboom, J., Glund, S., Verhamme, P., Bernstein, R. A., Dubiel, R., Huisman, M. V., Hylek, E. M., Kamphuisen, P. W., Kreuzer, J., Levy, J. H., Sellke, F. W., Stangier, J., Steiner, T., Wang, B., Kam, C.-W., & Weitz, J. I.
- Affiliations
- University Medical Center Groningen (NL)
- Boehringer Ingelheim (Germany) (DE)
- McMaster University (CA)
- KU Leuven (BE)
- Northwestern University (US)
- Leiden University (NL)
- Boston University (US)
- Heidelberg University (DE)
- Duke University (US)
- Brown University (US)
- Tuen Mun Hospital (CN)
- Thrombosis and Atherosclerosis Research Institute (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-08-06
- Volume
- 373
- Issue
- 6
- Pages
- 511-520
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1513839038
- Cited by
- 1,552
- References
- 1
- Citations by year
- 2026: 34 · 2025: 33 · 2024: 43 · 2023: 47 · 2022: 48 · 2021: 78 · 2020: 100 · 2019: 142 · 2018: 201 · 2017: 315 · 2016: 427 · 2015: 80
- FWCI
- 248.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Lirias (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Biochemistry › Blood transfusion and management
- Keywords
- idarucizumab, dabigatran, anticoagulant reversal, direct oral anticoagulants, major bleeding, ecarin clotting time, drug safety
- MeSH terms
- Dabigatran, Aged, Aged, 80 and over, Anticoagulants, Benzimidazoles, Blood Coagulation, Female, Hemorrhage, Humans, Infusions, Intravenous, Male, Middle Aged, Prospective Studies, Thrombosis, beta-Alanine, Antibodies, Monoclonal, Humanized
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