Charles V Pollack1, Paul A Reilly1, Joanne van Ryn1, John W Eikelboom1, Stephan Glund1, Richard A Bernstein1, Robert Dubiel1, Menno V Huisman1, Elaine M Hylek1, Chak-Wah Kam1, Pieter W Kamphuisen1, Jörg Kreuzer1, Jerrold H Levy1, Gordon Royle1, Frank W Sellke1, Joachim Stangier1, Thorsten Steiner1, Peter Verhamme1, Bushi Wang1, Laura Young1, Jeffrey I Weitz1. 1. From Thomas Jefferson University, Philadelphia (C.V.P.); Boehringer Ingelheim, Ridgefield, CT (P.A.R., R.D., B.W.); Boehringer Ingelheim, Biberach (J.R., S.G., J.S.), Boehringer Ingelheim, Ingelheim am Rhein (J.K.), Klinikum Frankfurt Höchst, Frankfurt (T.S.), and Heidelberg University Hospital, Heidelberg (T.S.) - all in Germany; McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada (J.W.E., J.I.W.); Feinberg School of Medicine, Northwestern University, Chicago (R.A.B.); Leiden University Medical Center, Leiden (M.V.H.), and Tergooi Hospital, Hilversum (P.W.K.) - both in the Netherlands; Boston University School of Medicine, Boston (E.M.H.); Tuen Mun Hospital, Hong Kong (C.-W.K.); Duke University School of Medicine, Durham, NC (J.H.L.); Middlemore Hospital (G.R.) and the University of Auckland (L.Y.) - both in Auckland, New Zealand; Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence (F.W.S.); and KU Leuven, Center for Molecular and Vascular Biology, Leuven, Belgium (P.V.).
Abstract
BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo 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 diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .).
BACKGROUND:Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo 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 diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .).
Authors: Tomáš Bolek; Matej Samoš; Ingrid Škorňová; Lucia Stančiaková; Ján Staško; Peter Galajda; Peter Kubisz; Marián Mokáň Journal: Drugs Aging Date: 2018-06 Impact factor: 3.923
Authors: Daniel M Witt; Robby Nieuwlaat; Nathan P Clark; Jack Ansell; Anne Holbrook; Jane Skov; Nadine Shehab; Juliet Mock; Tarra Myers; Francesco Dentali; Mark A Crowther; Arnav Agarwal; Meha Bhatt; Rasha Khatib; John J Riva; Yuan Zhang; Gordon Guyatt Journal: Blood Adv Date: 2018-11-27