Idarucizumab for dabigatran reversal: A systematic review and meta-analysis of indications and outcomes

Background: Idarucizumab has been approved to reverse the anticoagulant effect of dabigatran. However, there is little knowledge of the effectiveness and safety of idarucizumab in daily practice. Aims: This systematic review and meta-analysis aims to evaluate the use, effectiveness and outcomes of idarucizumab. Methods: A systematic literature search was performed up to September 8th 2022. Original studies including patients prescribed idarucizumab, evaluating prescription indications, prescription appropriateness, haemostatic efficacy and/or the occurrence of adverse events were eligible. Case-reports and studies performed in patients ≤18 years or in healthy volunteers were excluded. Study selection and data extraction were performed by two independent reviewers. Pooled estimates were calculated using the random-effects model, after Freeman-Tukey double-arcsine transformation. Results: Thirty studies comprising 3602 patients were included. Idarucizumab was prescribed for bleeding (63.1 %, 95%CI 57.0 %–69.0 %), invasive procedures (30.5 %, 95%CI: 24.1 %–37.2 %), to enable thrombolysis (range: 2.0 %–27.3 %), dabigatran intoxication without bleeding (range: 3.6 %–7.0 %) or unspecified reasons (range: 0.4 %–18.8 %). Overall, 2.8 % (95%CI 0.5 %–6.2 %) of prescription indications were reported to be inappropriate upon post-hoc evaluation. Hemostatic effectiveness was achieved in 77.7 % (95%CI 66.7 %–87.2 %) and peri-procedural haemostasis was normal in 98.5 % (95%CI 86.6 %–100 %) of patients. The pooled incidences of all-cause mortality and thromboembolic events at any follow-up duration were 13.6 % (95%CI 9.6 %–17.9 %) and 2.0 % (95%CI 0.8 %–3.4 %), respectively. Conclusion: Idarucizumab was mainly prescribed in the setting of bleeding. The reported hemostatic effectiveness was good, especially perioperatively, and the incidence of thromboembolic events was low. Patients with dabigatran-associated bleeding or requiring an urgent procedure nonetheless face a high mortality risk.