Low- versus Standard-Dose Intravenous Alteplase in the Context of Bridging Therapy for Acute Ischemic Stroke: A Korean ENCHANTED Study

Jong S Kim, Yeon-Jung Kim, Kyung Bok Lee, Jae Kwan Cha, Jong-Moo Park, Yangha Hwang, Eung-Gyu Kim, Joung-Ho Rha, Jaseong Koo, Jei Kim, Yong-Jae Kim, Woo-Keun Seo, Dong-Eog Kim, Thompson G Robinson, Richard I Lindley, Xia Wang, John Chalmers, Craig S Anderson, Jong S Kim, Yeon-Jung Kim, Kyung Bok Lee, Jae Kwan Cha, Jong-Moo Park, Yangha Hwang, Eung-Gyu Kim, Joung-Ho Rha, Jaseong Koo, Jei Kim, Yong-Jae Kim, Woo-Keun Seo, Dong-Eog Kim, Thompson G Robinson, Richard I Lindley, Xia Wang, John Chalmers, Craig S Anderson

Abstract

Background and purpose: Following the positive results from recent trials on endovascular therapy (EVT), bridging therapy (intravenous alteplase plus EVT) is increasingly being used for the treatment of acute ischemic stroke. However, the optimal dose of intravenous alteplase remains unknown in centers where bridging therapy is actively performed. The optimal dose for eventual recanalization and positive clinical outcomes in patients receiving bridging therapy also remains unknown.

Methods: In this prospective Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) sub-study, we explored the outcomes following treatment with two different doses (low- [0.6 mg/kg] or standard-dose [0.9 mg/kg]) of intravenous alteplase across 12 Korean centers where EVT is actively performed. The primary endpoint was a favorable outcome at 90 days (modified Rankin Scale scores 0 to 1). Secondary endpoints included symptomatic intracerebral hemorrhage (ICH) in all patients, and the recanalization rate and favorable outcome in patients who underwent cerebral angiography for EVT (ClinicalTrials.gov, number NCT01422616).

Results: Of 351 patients, the primary outcome occurred in 46% of patients in both the standard-(80/173) and low-dose (81/178) groups (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.72 to 1.81; P=0.582), although ICHs tended to occur more frequently in the standard-dose group (8% vs. 3%, P=0.056). Of the 67 patients who underwent cerebral angiography, there was no significant difference in favorable functional outcome between the standard- and low-dose groups (39% vs. 21%; OR, 2.39; 95% CI, 0.73 to 7.78; P=0.149).

Conclusions: There was no difference in functional outcome between the patients receiving different doses of alteplase in centers actively performing bridging therapy.

Keywords: Cerebral infarction; Intracranial hemorrhages; Thrombectomy.

Figures

Figure 1.
Figure 1.
Number of patients who were enrolled, randomly assigned to a study group, and included in the intertion-to-treat and per-protocol populations. The modified intention-to-treat population included patients who were randomized and received alteplase. The per-protocol population included patients who met the criteria of the modified intention-to treat population, had a final diagnosis of ischemic stroke, and completed follow-up.
Figure 2.
Figure 2.
Distribution of scores on the modified Rankin Scale (mRS). The distribution of mRS score is shown for the intention-to-treat population, per-protocol population, and cerebral angiography subgroup at the 90-day follow-up. rt-PA, recombinant tissue plasminogen activator.

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