Abstract | BACKGROUND: METHODS: Patients with uncontrollable GI bleeding requiring reversal were enrolled from June 2014 through July 2016 in the RE-VERSE AD study (Reversal of Dabigatran Anticoagulant Effect With Idarucizumab), a prospective, multicenter, open-label study of idarucizumab, and were followed up for 90 days for primary and secondary outcomes. Patients were to receive a 5-g dose of intravenous idarucizumab, administered as 2 bolus infusions of 2.5 g no more than 15 minutes apart. The primary end point was the maximum reversal of dabigatran anticoagulation within 4 hours after administration of idarucizumab as measured by the dabigatran-specific assays diluted thrombin time and ecarin clotting time. Further end points included investigator-reported bleeding cessation within the first 24 hours and incidence of rebleeding, thromboembolic events, or mortality. RESULTS: GI bleeding occurred in 137 patients enrolled in RE-VERSE AD, of which 84% was adjudicated as major or life-threatening, 48 (35.0%) was upper GI tract in origin, 43 (31.4%) was lower GI in origin, and 46 (33.6%) was either both or unknown. Complete reversal of dabigatran was observed in 118 of 121 patients (97.5%) with an elevated diluted thrombin time at presentation and 95 of 131 patients (72.5%) with an elevated ecarin clotting time and was similar for upper and lower GI bleeding. Bleeding cessation within 24 hours was reported in 92 of 134 evaluable patients (68.7%) after a median duration of 2.4 hours (interquartile range, 2.0-3.9 hours). During the 90-day follow-up, 6 patients (4.4%) had a postreversal thromboembolic event, and 20 patients (14.6%) died. CONCLUSIONS:
Idarucizumab showed a rapid and complete reversal of dabigatran activity in nearly all patients presenting with GI bleeding, facilitating emergency patient care without the additional presence of anticoagulation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02104947.
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Authors | Sake J Van der Wall, Renato D Lopes, James Aisenberg, Paul Reilly, Joanne van Ryn, Stephan Glund, Amelie Elsaesser, Frederikus A Klok, Charles V Pollack Jr, Menno V Huisman |
Journal | Circulation
(Circulation)
Vol. 139
Issue 6
Pg. 748-756
(02 05 2019)
ISSN: 1524-4539 [Electronic] United States |
PMID | 30586692
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Anticoagulants
- Vitamin K
- idarucizumab
- Dabigatran
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Topics |
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Humanized
(adverse effects, therapeutic use)
- Anticoagulants
(adverse effects, therapeutic use)
- Dabigatran
(adverse effects, therapeutic use)
- Drug Substitution
- Drug-Related Side Effects and Adverse Reactions
(epidemiology)
- Female
- Follow-Up Studies
- Gastrointestinal Hemorrhage
(epidemiology, etiology)
- Humans
- Male
- Middle Aged
- Prospective Studies
- Risk Assessment
- United States
(epidemiology)
- Venous Thromboembolism
(drug therapy, epidemiology)
- Vitamin K
(antagonists & inhibitors)
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