Idarucizumab in Dabigatran-Treated Patients with Acute Ischemic Stroke Receiving Alteplase: A Systematic Review of the Available Evidence

Abstract

Background and PurposeCurrent guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke.MethodsWe performed a systematic review of all published cases of intravenous tissue plasminogen activator treatment following the administration of a dabigatran antidote up to June 2017 and added five unpublished cases of our own. We analyzed clinical and radiological outcomes, symptomatic post-thrombolysis intracranial hemorrhage, and other serious systemic bleeding. Additional endpoints were allergic reaction to idarucizumab, and venous thrombosis in the post-acute phase.ResultsWe identified a total of 21 patients (71% male) with a median age of 76 years (interquartile range 70–84). The median National Institute of Health Stroke Scale score at baseline was 10 (n = 20, interquartile range 5–11) and 18/20 patients (90%) had mild or moderate stroke severity. The time from symptom onset to start of tissue plasminogen activator was 155 min (n = 18, interquartile range 122–214). The outcome was unfavorable in 3/19 patients (16%). There was one fatality as a result of a symptomatic post-thrombolysis intracranial hemorrhage, and two patients experienced an increase in the National Institute of Health Stroke Scale compared with baseline. One patient had a recurrent stroke. No systemic bleeding, venous thrombosis, or allergic reactions were reported.ConclusionExperience with idarucizumab administration prior to tissue plasminogen activator treatment in acute ischemic stroke is limited. Initial clinical experience in less severe stroke syndromes and short time windows seems favorable. Larger cohorts are required to confirm safety, including bleeding complications and the risk of thrombosis.

Idarucizumab for Emergency Reversal of Anticoagulant Effects of Dabigatran: Interim Results of a Japanese Post-Marketing Surveillance Study

“…In this interim analysis, nine patients were treated with idarucizumab before treatment of ischemic stroke (thrombolysis, thrombectomy, or bypass for ischemic stroke). Several case reports suggest that thrombolysis and thrombectomy can be performed safely after dabigatran reversal with idarucizumab [22,23]. Although these data are limited, recommendations have been published regarding acute reperfusion therapy with idarucizumab for patients with ischemic stroke receiving dabigatran [24,25].…”

Intravenous thrombolysis in stroke after dabigatran reversal with idarucizumab: case series and systematic review

“…Moreover, in this systematic review, stroke severity increased, with moderate to severe stroke in 63% of cases (vs 10%4), and median time to IVT increasing to 173 min (vs 155 min4). Despite increasing stroke severity and time to IVT, the rate of favourable outcomes is higher than previously reported (81.9% vs 72%), suggesting that the treatment paradigm might be considered also for all patients with acute ischaemic stroke, including those with moderate to severe stroke and longer time windows for IVT.…”

“…Compared with the existing systematic review,4 we have been able to double included papers (24 vs 13) and enlarge the cohort of more than a third (55 patients vs 40). Moreover, in this systematic review, stroke severity increased, with moderate to severe stroke in 63% of cases (vs 10%4), and median time to IVT increasing to 173 min (vs 155 min4).…”

Systemic thrombolysis and endovascular thrombectomy in severe acute ischemic stroke after dabigatran reversal with idarucizumab

“…Previously published cases usually had good outcomes as well, but were generally of lower initial severity . A systematic review of 21 patients with a median baseline NIHSS of 10 by Pikija et al identified 16% of unfavorable outcome (increase in NIHSS, recurrent stroke, symptomatic post‐thrombolysis intracranial hemorrhage, or death). No systemic bleeding, venous thrombosis, or allergic reactions were reported.…”