Low-Dose vs. Standard-Dose Intravenous Alteplase in Bridging Therapy Among Patients With Acute Ischemic Stroke: Experience From a Stroke Center in Vietnam.

Duy Ton Mai,Anh Tuan Tran,Viet Phuong Dao,Ha Quan Phan,Quoc Viet Bui,Xuan Trung Vuong,Dang Luu Vu,Hoang Thi Phan,Hoang Kien Le,Quang Anh Nguyen,Van Chi Nguyen,Hoang Nguyen,Tien Dung Nguyen,Phuc Duc Dang,Quang Tho Pham

doi:10.3389/fneur.2021.653820

Abstract

Background: To date, the role of bridging intravenous thrombolysis before mechanical thrombectomy (MTE) is controversial but still recommended in eligible patients. Different doses of intravenous alteplase have been used for treating patients with acute ischemic stroke from large-vessel occlusion (LVO-AIS) in Asia, largely due to variations in the risks for intracerebral hemorrhage (ICH) and treatment affordability. Uncertainty exists over the potential benefits of treating low-dose alteplase, as opposed to standard-dose alteplase, prior to MTE among patients with LVO-AIS.Aim: The aim of the study was to compare outcomes of low- vs. standard-dose of bridging intravenous alteplase before MTE among LVO-AIS patients.Methods: We performed a retrospective analysis of LVO-AIS patients who were treated with either 0.6 mg/kg or 0.9 mg/kg alteplase prior to MTE at a stroke center in Northern Vietnam. Multivariable logistic regression models, accounting for potential confounding factors including comorbidities and clinical factors (e.g., stroke severity), were used to compare the outcomes between the two groups. Our primary outcome was functional independence at 90 days following stroke (modified Rankin score; mRS ≤ 2). Secondary outcomes included any ICH incidence, early neurological improvement, recanalization rate, and 90-day mortality.Results: We analyzed data of 107 patients receiving bridging therapy, including 73 with low-dose and 34 with standard-dose alteplase before MTE. There were no statistically significant differences between the two groups in functional independence at 90 days (adjusted OR 1.02, 95% CI 0.29–3.52) after accounting for potential confounding factors. Compared to the standard-dose group, patients with low-dose alteplase before MTE had similar rates of successful recanalization, early neurological improvement, 90-day mortality, and ICH complications.Conclusion: In the present study, patients with low-dose alteplase before MTE were found to achieve comparable clinical outcomes compared to those receiving standard-dose alteplase bridging with MTE. The findings suggest potential benefits of low-dose alteplase in bridging therapy for Asian populations, but this needs to be confirmed by further clinical trials.

Highlights

The role of bridging thrombolysis before mechanical thrombectomy (MTE) has been controversial [1], but it is still recommended in eligible patients [1,2,3,4]
We included 107 patients (63% males; mean age: 63 years) who were treated with intravenous alteplase prior to MTE
They were divided into two groups according to the bridging therapy they received: 73 were treated with a lower dose of intravenous alteplase (0.6 mg/kg) and MTE between 2017 and 2018, and 34 were treated with a standard dose of intravenous alteplase (0.9 mg/kg) and MTE in 2019

Summary

Introduction

The role of bridging thrombolysis before mechanical thrombectomy (MTE) has been controversial [1], but it is still recommended in eligible patients [1,2,3,4]. The SKIP (The Randomized Study of EVT With Vs. Without Intravenous Recombinant Tissue-Type Plasminogen Activator in Acute Stroke With ICA and M1 Occlusion) trial, which included patients with LVO-AIS in Japan, was unable to demonstrate the noninferiority of MTE alone over bridging therapy with low-dose alteplase before MTE [6]. The DIRECT-MT (Direct Intraarterial Thrombectomy in Order to Revascularize Acute Ischemic Stroke Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals) trial conducted in China showed that MTE alone was non-inferior (≤20% margin of confidence) to MTE preceded by standard-dose alteplase with regard to the primary outcome (90-day modified Rankin Scale shift) [7]. The DEVT (Direct Endovascular Thrombectomy vs Combined IVT and Endovascular Thrombectomy for Patients With Acute Large Vessel Occlusion in the Anterior Circulation) trial in China demonstrated the non-inferiority of primary MTE treatment over the bridging therapy (standard-dose IVT + MTE) in functional independence (noninferiority margin of 10%) [8]. Uncertainty exists over the potential benefits of treating low-dose alteplase, as opposed to standard-dose alteplase, prior to MTE among patients with LVO-AIS

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Results