• Prescrire Int. 2016 Nov 1; 25 (176): 260-263.

AbstractDabigatran, an oral anticoagulant that acts by inhibiting thrombin, was first marketed in the European Union in 2008. No antidote has been available, complicating the management of patients who have severe bleeding or require emergency surgery. In late 2015, idarucizumab, a monoclonal antibody directed against dabigatran, was authorised in the European Union as a specific antidote for dabigatran. It is administered intravenously. In early 2016, most data on the efficacy of idarucizumab come from an interim analysis of a non-comparative trial in 123 dabigatran-treated patients who had serious bleeding or required emergency surgery or invasive procedures. All 123 patients received idarucizumab. Twenty-six patients died, 8 from bleeding. Among the 66 patients with bleeding, the duration of the event could not be determined in 18 cases because the site of bleeding was not visible. Among the other 48 patients, the bleeding stopped in 44 cases after a median of about 10 hours. Fifty-two of the 57 patients who received idarucizumab prior to invasive procedures underwent surgery. The surgeons considered their clotting status to be normal in 48 cases and mildly or moderately abnormal in the other 4 cases. The role of idarucizumab in these outcomes is difficult to assess for several reasons, including: the lack of a comparator; the partly subjective end-points as the use of idarucizumab was known; and failure to take into account the natural rate of dabigatran elimination. Although idarucizumab normalised markers of dabigatran activity in most patients, the clinical impact was not reported in terms of the frequency of bleeding or thrombosis. The EU summary of product characteristics states that a second dose of idarucizumab can be administered in case of marked dabigatran exposure (massive ingestion, severe renal impairment), but this was the case for only two patients included in the clinical trial. Few data on the adverse effects of idarucizumab are available. Idarucizumab carries a risk of hypersensitivity reactions and of developing anti-idarucizumab antibodies, with unknown consequences. In practice, in 2016, close monitoring of patients on dabigatran and standard management of bleeding and its consequences remain the priority. The clinical effects of idarucizumab are poorly documented. Authorisation of this antidote should not lead to trivialising the use of dabigatran. In 2016, warfarin, a vitamin K antagonist, is the standard oral anticoagulant for most patients, despite its inconvenience.

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