Bridging Therapy Versus Direct Mechanical Thrombectomy in Patients with Acute Ischemic Stroke due to Middle Cerebral Artery Occlusion: A Clinical- Histological Analysis of Retrieved Thrombi.

Original Article Bridging Therapy Versus Direct Mechanical Thrombectomy in Patients with Acute Ischemic Stroke due to Middle Cerebral Artery Occlusion: A ClinicalHistological Analysis of Retrieved Thrombi Cell Transplantation 2019, Vol. 28(6) 684–690 ª The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/0963689718823206 journals.sagepub.com/home/cll Li Gong1 , Xiaoran Zheng1, Lijin Feng2, Xiang Zhang3, Qiong Dong1, Xiaoyu Zhou1, Haichao Wang1, Xiaojun Zhang4, Zhongwen Shu3, Yanxin Zhao1, and Xueyuan Liu1 Abstract Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n ¼ 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P ¼ 0.042) and lower fibrin (P ¼ 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P ¼ 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin. Keywords red blood cells, fibrin, mechanical thrombectomy, cardioembolism, large-artery atherosclerosis 1 Introduction Five previously reported randomized clinical trials demonstrated the efficacy and safety of direct mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) caused by large-artery occlusions1–5. Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) administered within 4.5 hours of an AIS has been the standard treatment. However, patients with stroke due to a large-artery occlusion respond poorly to intravenous rt-PA alone6–8. Therefore, the debates regarding whether intravenous rt-PA before MT is necessary are ongoing. Moreover, some patients underwent direct mechanical thrombectomy mainly for contraindications to IVT and other patients for a suspicion of large thrombi, borderline Department of Neurology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China 2 Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China 3 Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China 4 Department of Intervention, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China Submitted: July 26, 2018. Revised: November 28, 2018. Accepted: December 4, 2018. Corresponding Authors: Xueyuan Liu, Department of Neurology, Shanghai Tenth People’s Hospital, Tongji University, 301# Middle Yanchang Road, Shanghai 200072, China; Yanxin Zhao, Department of Neurology, Shanghai Tenth People’s Hospital, Tongji University, 301# Middle Yanchang Road, Shanghai 200072, China. Emails: (XYL); (YXZ) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). Gong et al coagulation status, time window close to 4.5 hours, etc. Therefore, comparing the characteristics of these patients with those of bridging therapy patients is not optimal9. Several previously reported studies did not support the idea that IVT before MT in patients with large-artery occlusions could provide an additional clinical benefit compared with MT alone2,10. However, the occlusion sites in those studies included both the middle cerebral artery (MCA) and internal carotid artery (ICA), suggesting different stroke subtypes and responses to IVT. In Asians, the incidence of MCA occlusion is significantly higher than that of ICA occlusion. Therefore, separating patients with MCA occlusion from those with ICA occlusion to avoid betweengroup variance may be necessary. The application of MT allows for a histological analysis of the clots retrieved from the intracranial arteries. Recent studies suggested that a histological examination of retrieved clots can offer new insights into the pathogenesis of acute strokes that are caused by intracranial large-artery occlusion11–12. However, few studies have actually analyzed the thrombus compositions, which were naturally affected by rtPA, between the patients who underwent bridging therapy and direct MT. Furthermore, data on the correlation between clot composition and stroke subtypes in patients with MCA occlusion are still limited. Therefore, the aim of our study was to evaluate whether the functional outcomes of bridging therapy and direct MT are similar in IVT-eligible patients with MCA occlusion, and to further examine thrombus composition and its relationship with stroke subtypes. Materials and Methods Patients A total of 73 consecutive patients with AIS and MCA occlusion were enrolled from December 2015 to January 2018. Patients had their MT performed using the Solitaire AB stent retriever (Covidien, Irvine, CA, USA). Patients were excluded if they were treated with IVT only, had contraindications for IVT and missed key outcome data, or had follow-up loss at 3 months. The patients’ baseline characteristic (...truncated)