Endovascular Therapy for Acute Stroke with a Large Ischemic Region.

BACKGROUND: Endovascular therapy for acute ischemic stroke is generally avoided when the infarction is large, but the effect of endovascular therapy with medical care as compared with medical care alone for large strokes has not been well studied. METHODS: We conducted a multicenter, open-label, randomized clinical trial in Japan involving patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) value of 3 to 5 (on a scale from 0 to 10, with lower values indicating larger infarction). Patients were randomly assigned in a 1:1 ratio to receive endovascular therapy with medical care or medical care alone within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images. Alteplase (0.6 mg per kilogram of body weight) was used when appropriate in both groups. The primary outcome was a modified Rankin scale score of 0 to 3 (on a scale from 0 to 6, with higher scores indicating greater disability) at 90 days. Secondary outcomes included a shift across the range of modified Rankin scale scores toward a better outcome at 90 days and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours. RESULTS: A total of 203 patients underwent randomization; 101 patients were assigned to the endovascular-therapy group and 102 to the medical-care group. Approximately 27% of patients in each group received alteplase. The percentage of patients with a modified Rankin scale score of 0 to 3 at 90 days was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval [CI], 1.35 to 4.37; P = 0.002). The ordinal shift across the range of modified Rankin scale scores generally favored endovascular therapy. An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (relative risk, 3.51; 95% CI, 1.76 to 7.00), and any intracranial hemorrhage occurred in 58.0% and 31.4%, respectively (P<0.001). CONCLUSIONS: In a trial conducted in Japan, patients with large cerebral infarctions had better functional outcomes with endovascular therapy than with medical care alone but had more intracranial hemorrhages. (Funded by Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy; RESCUE-Japan LIMIT ClinicalTrials.gov number, NCT03702413.).

Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.