Yoshimura Shinichi, Sakai Nobuyuki, Yamagami Hiroshi, Uchida Kazutaka, Beppu Mikiya, Toyoda Kazunori, Matsumaru Yuji, Matsumoto Yasushi, Kimura Kazumi, Takeuchi Masataka, Yazawa Yukako, Kimura Naoto, Shigeta Keigo, Imamura Hirotoshi, Suzuki Ichiro, Enomoto Yukiko, Tokunaga So, Morita Kenichi, Sakakibara Fumihiro, Kinjo Norito, Saito Takuya, Ishikura Reiichi, Inoue Manabu, Morimoto Takeshi
From the Departments of Neurosurgery (S.Y., K.U., M.B., F.S., N. Kinjo) and Clinical Epidemiology (K.U., F.S., N. Kinjo, T.S., T.M.), Hyogo College of Medicine, Nishinomiya, the Departments of Neurosurgery (N.S., H.I.) and Diagnostic Radiology (R.I.), Kobe City Medical Center General Hospital, Kobe, the Department of Stroke Neurology, National Hospital Organization Osaka National Hospital, Osaka (H.Y.), the Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita (K.T., M.I.), the Division of Stroke Prevention and Treatment, Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Ibaraki (Y. Matsumaru), the Department of Neuroendovascular Therapy (Y. Matsumoto) and the Department of Stroke Neurology (Y.Y., T.S.), Kohnan Hospital, Sendai, the Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo (K.K.), the Department of Neurosurgery, Seisho Hospital, Odawara (M.T.), the Department of Neurosurgery, Iwate Prefectural Central Hospital, Morioka (N. Kimura), the Department of Neurosurgery, National Hospital Organization Disaster Medical Center, Tachikawa (K.S.), the Department of Neuroendovascular Therapy, Hachinohe City Hospital, Hachinohe (I.S.), the Department of Neurosurgery, Gifu University Hospital, Gifu (Y.E.), the Department of Neuroendovascular Therapy, National Hospital Organization Kyusyu Medical Center, Fukuoka (S.T.), and the Department of Cerebrovascular Medicine, Niigata City General Hospital, Niigata (K.M.) - all in Japan.
N Engl J Med. 2022 Apr 7;386(14):1303-1313. doi: 10.1056/NEJMoa2118191. Epub 2022 Feb 9.
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.
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.
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).
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.).
当梗死面积较大时，急性缺血性卒中的血管内治疗通常不被采用，但血管内治疗联合药物治疗与单纯药物治疗相比，对大面积卒中的疗效尚未得到充分研究。
我们在日本进行了一项多中心、开放标签、随机临床试验，纳入大脑大血管闭塞且影像学显示有大面积卒中的患者，阿尔伯塔卒中项目早期计算机断层扫描评分（ASPECTS）为3至5分（范围为0至10分，分数越低表明梗死面积越大）。患者按1:1比例随机分组，在最后一次已知健康状态后的6小时内接受血管内治疗联合药物治疗，或若液体衰减反转恢复图像无早期变化，则在24小时内接受单纯药物治疗。两组在适当情况下均使用阿替普酶（0.6毫克/千克体重）。主要结局是90天时改良Rankin量表评分为0至3分（范围为0至6分，分数越高表明残疾程度越高）。次要结局包括90天时改良Rankin量表评分范围向更好结局的转移，以及48小时时美国国立卫生研究院卒中量表（NIHSS）评分至少提高8分（范围为0至42分，分数越高表明缺损越严重）。
共有203例患者接受随机分组；101例患者被分配至血管内治疗组，102例患者被分配至药物治疗组。每组约27%的患者接受了阿替普酶治疗。血管内治疗组90天时改良Rankin量表评分为0至3分的患者百分比为31.0%，药物治疗组为12.7%（相对风险，2.43；95%置信区间[CI]，1.35至4.37；P = 0.002）。改良Rankin量表评分范围的序贯转移总体上有利于血管内治疗。血管内治疗组31.0%的患者在48小时时NIHSS评分至少提高8分，药物治疗组为8.8%（相对风险，3.51；95%CI，1.76至7.00），颅内出血发生率分别为58.0%和31.4%（P<0.001）。
在日本进行的一项试验中，大脑大面积梗死患者接受血管内治疗比单纯药物治疗具有更好的功能结局，但颅内出血更多。（由三原脑血管疾病研究促进基金和日本神经血管内治疗学会资助；RESCUE - Japan LIMIT临床试验注册号，NCT03702413。）
