Idarucizumab for Reversion of Anticoagulant Effect in Daily Practice

Abstract

The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) seen in the respective pivotal randomized trials on stroke prevention in atrial fibrillation (AF) 1 have been broadly confirmed by numerous observational cohort-or registry-based reports. [2][3][4] In addition to the convenient practical aspects favouring NOACs over vitamin K antagonists (e.g., no need for continuous laboratory monitoring, limited drug-drug and food interactions, fixed-dose regimen), the availability of specific antidote(s) to reverse their anticoagulant effect has been conditioned for a more widespread and possibly safer use of NOACs. 5,6 Several antidotes/reversal agents for NOACs have been recently developed. 7 Idarucizumab, a specific reversal agent for dabigatran, has been the first to receive approval for clinical use in many countries.The efficacy and safety of idarucizumab for reversing dabigatran anticoagulant effect has been tested in the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) phase III study. 8 In this multicentre, prospective, single-cohort study, 503 patients receiving dabigatran were enrolled to receive idarucizumab 5 g in two consecutive intravenous boluses. The primary efficacy endpoint was maximum percentage of dabigatran anticoagulant effect reversal within 4 hours of the second idarucizumab intravenous bolus. The patients were divided into two groups: those with an uncontrollable or life-threatening major bleeding were enrolled in group A and those needing surgery or another invasive procedure requiring normal haemostasis were enrolled in group B. The two groups were similar regarding most baseline characteristics; diluted thrombin time and ecarin clotting time were prolonged in more than 90% of patients at study entry but normalized rapidly after the first idarucizumab infusion, with 100% reversal within 4 hours after infusion. The reversal was sustained up to 24 hours. Among patients in group A for which the assessment of bleeding cessation could have been performed, 68% had bleeding cessation within 24 hours. For the patients in group B, peri-procedural haemostasis was considered normal in 93% patients. In the follow-up observation, 30-day mortality rates were similar between the two groups (13.5 and 12.6% for groups A and B, respectively). Thrombotic events occurred in 4.8% of the entire cohort.Until recently, only small case series about idarucizumab use have been reported, 9-11 and a larger study of a cohort from 20 hospitals in the Netherlands analysed 88 patients (53 with severe bleeding and 35 requiring urgent surgical intervention). 12 Effective haemostasis was achieved in twothirds of bleeding patients and was associated with lower mortality risk. Clinical outcomes were considered similar to those observed in the RE-VERSE AD trial, regarding recurrent bleeding, thromboembolism and a high mortality rate.In this issue of the journal, Fanikos et al report results of the RE-VECTO study, a global post-approval, European regulatory authorities requested international...

Thrombosis and Haemostasis 2019 Editor's Choice Papers

“…Already among our most read papers, the recent report of the global international surveillance program RE-VECTO study, 56 included 359 patients from 61 sites in Asia, European Union and North America and is the largest so far to evaluate idarucizumab in 'real-world' clinical practice worldwide. 57 New indications of OACs should rapidly emerge especially as OAC studies are pending. As mentioned previously, children with cancer in particular, may benefit from thromboprophylaxis implicating novel therapeutic strategies.…”

Safety of idarucizumab in the reversal of dabigatran at six tertiary care Ontario hospitals

“…8 While large trials are crucial in establishing the efficacy and safety of new drugs, real-world practice can differ from what is seen within the realm of clinical studies, including different patient demographics, clinical circumstances, and practice patterns. 9,10 To assess real-world use of idarucizumab, we analyzed its use at six tertiary care centers.…”