Systolic pressure target after endovascular thrombectomy in acute large-vessel occlusion ischemic stroke patients: Comment on ENCHANTED2/MT

Brain-X Pub Date : 2023-03-21 DOI:10.1002/brx2.4
Yunpeng Yuan, Baozhu Wei, Wenyun Zhu, Yang Liu, Yingfeng Wan
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The guideline<span><sup>2</sup></span> recommends a systolic pressure of &lt;180 mmHg before and after mechanical thrombectomy without randomized clinical trial evidence.</p><p>Recently, Yang et al.<span><sup>3</sup></span> reported the results of the multicenter, open-label, blinded-endpoint, and randomized controlled trial ENCHANTED2/MT, which aimed to determine if a more aggressive blood pressure goal is beneficial in patients with acute ischemic stroke. Patients were required to have a diagnosis of large-vessel occlusion acute ischemic stroke and a successful endovascular thrombectomy procedure followed by hypertension (defined as ≥2 successive measurements of systolic blood pressure ≥140 mmHg for &gt;10 min). The randomization arms were &lt;120 mmHg versus 140–180 mmHg for 72 h, and the primary outcome was assessed by a shift analysis of the modified Rankin Scale at 90 days. The 821 patients who were prospectively enrolled between 2020 and 2022 were randomized, and the source populations were derived from 44 hospitals in China. The trial was suspended in June 2022 due to safety concerns after an independent data and safety monitoring board reviewed the data. Unexpectedly, the primary results were that the more intensive treatment group was more likely to have worse outcomes and higher early neurological deterioration and disability rates than the less intensive treatment group.</p><p>This study again proved the complex relationship between blood pressure and functional outcomes after acute large-vessel occlusion ischemic stroke.<span><sup>1</sup></span> This is an important trial that was built on accumulating observational data in the field and provided randomized trial evidence that more intensive blood pressure lowering (&lt;120 mmHg) is not only neutral but harmful. In this regard, this study is of broad general interest to emergency departments and stroke centers, as blood pressure is a parameter that must be managed in all stroke patients' post-procedures.</p><p>However, several points need to be noted and comprehensively discussed before interpreting the results and applying them clinically. First, fig. 2 from the ENCHANTED2/MT trial paper<span><sup>3</sup></span> suggested that a systolic pressure of &lt;120 mmHg was only narrowly achieved in the more intensive treatment group during the first 3 days. Although current guidelines<span><sup>2</sup></span> recommend a blood pressure of &lt;180 mmHg, no optimal blood pressure target for patients with ischemic stroke who undergo mechanical thrombectomy has been identified to date.<span><sup>1</sup></span> Taken together, doctors may need to employ individualized targets for systolic pressure control after mechanical thrombectomy based on the patient's prior medical history and current blood pressure condition as well as the success of occluded vessel recanalization. Second, blood pressure is elevated in approximately 75% of patients with acute stroke and usually decreases spontaneously over the subsequent few days.<span><sup>4</sup></span> In the ENCHANTED2/MT trial,<span><sup>3</sup></span> 267 (66%) patients in the more intensive treatment group and 261 (64%) patients in the less intensive treatment group had premorbid hypertension, limiting the likelihood that the post-stroke outcomes were due to premorbid hypertension rates. Spontaneous post-stroke hypertension may be a compensatory response to ischemic stroke; thus, relatively low blood pressure may be partly responsible for worse functional outcomes in the more intensive treatment group. 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引用次数: 0

Abstract

Patients with large-vessel occlusion ischemic stroke continue to have high mortality and disability rates after mechanical thrombectomy with or without intravenous alteplase treatment. Elevated blood pressure during the perioperative period is associated with higher mortality and disability prevalence rates.1 Thus, lowering post-procedure systolic pressure is a potential approach to improving patients' outcomes. The guideline2 recommends a systolic pressure of <180 mmHg before and after mechanical thrombectomy without randomized clinical trial evidence.

Recently, Yang et al.3 reported the results of the multicenter, open-label, blinded-endpoint, and randomized controlled trial ENCHANTED2/MT, which aimed to determine if a more aggressive blood pressure goal is beneficial in patients with acute ischemic stroke. Patients were required to have a diagnosis of large-vessel occlusion acute ischemic stroke and a successful endovascular thrombectomy procedure followed by hypertension (defined as ≥2 successive measurements of systolic blood pressure ≥140 mmHg for >10 min). The randomization arms were <120 mmHg versus 140–180 mmHg for 72 h, and the primary outcome was assessed by a shift analysis of the modified Rankin Scale at 90 days. The 821 patients who were prospectively enrolled between 2020 and 2022 were randomized, and the source populations were derived from 44 hospitals in China. The trial was suspended in June 2022 due to safety concerns after an independent data and safety monitoring board reviewed the data. Unexpectedly, the primary results were that the more intensive treatment group was more likely to have worse outcomes and higher early neurological deterioration and disability rates than the less intensive treatment group.

This study again proved the complex relationship between blood pressure and functional outcomes after acute large-vessel occlusion ischemic stroke.1 This is an important trial that was built on accumulating observational data in the field and provided randomized trial evidence that more intensive blood pressure lowering (<120 mmHg) is not only neutral but harmful. In this regard, this study is of broad general interest to emergency departments and stroke centers, as blood pressure is a parameter that must be managed in all stroke patients' post-procedures.

However, several points need to be noted and comprehensively discussed before interpreting the results and applying them clinically. First, fig. 2 from the ENCHANTED2/MT trial paper3 suggested that a systolic pressure of <120 mmHg was only narrowly achieved in the more intensive treatment group during the first 3 days. Although current guidelines2 recommend a blood pressure of <180 mmHg, no optimal blood pressure target for patients with ischemic stroke who undergo mechanical thrombectomy has been identified to date.1 Taken together, doctors may need to employ individualized targets for systolic pressure control after mechanical thrombectomy based on the patient's prior medical history and current blood pressure condition as well as the success of occluded vessel recanalization. Second, blood pressure is elevated in approximately 75% of patients with acute stroke and usually decreases spontaneously over the subsequent few days.4 In the ENCHANTED2/MT trial,3 267 (66%) patients in the more intensive treatment group and 261 (64%) patients in the less intensive treatment group had premorbid hypertension, limiting the likelihood that the post-stroke outcomes were due to premorbid hypertension rates. Spontaneous post-stroke hypertension may be a compensatory response to ischemic stroke; thus, relatively low blood pressure may be partly responsible for worse functional outcomes in the more intensive treatment group. Third, it is noteworthy that there was no difference in symptomatic intracerebral hemorrhage rates between the two groups, consistent with the previously published BP-TARGET trial,5 in which an aggressive systolic pressure goal of 100–129 mmHg after successful reperfusion in patients with ischemic stroke did not reduce intracerebral hemorrhage rates at 24–36 h when compared to a standard care systolic blood pressure goal of 130–185 mmHg, suggesting either a lack of protection at this level of more intensive treatment of systolic pressure or a lack of harm at this level of less intensive treatment of systolic pressure regarding symptomatic intraparenchymal hemorrhage transformation.

To answer the question of what the optimal systolic pressure target should be after mechanical thrombectomy in patients with acute large-vessel occlusion stroke, the results of ongoing relevant clinical trials and in future, more rigorously designed clinical trials are required.

Yunpeng Yuan: Writing – original draft. Baozhu Wei: Writing – original draft: Wenyun Zhu: Writing – original draft. Yang Liu: Writing – original draft. Yingfeng Wan: Writing – original draft.

Yunpeng Yuan, Baozhu Wei, Wenyun Zhu, Yang Liu, and Yingfeng Wan declare no conflicts of interest.

Not applicable.

急性大血管闭塞缺血性脑卒中患者血管内血栓切除术后的收缩压靶点:对ENCHANTED2/MT的评价
大血管闭塞缺血性卒中患者在接受或不接受阿替普酶静脉注射治疗的机械血栓切除术后,死亡率和致残率仍然很高。围手术期血压升高与较高的死亡率和残疾发生率相关。1因此,降低术后收缩压是改善患者预后的一种潜在方法。指南线2推荐&lt;机械血栓切除术前后180 mmHg,无随机临床试验证据。最近,Yang等人3报道了多中心、开放标签、盲终点和随机对照试验ENCHANTED2/MT的结果,该试验旨在确定更积极的血压目标是否对急性缺血性卒中患者有益。要求患者诊断为大血管闭塞性急性缺血性中风,并成功进行血管内血栓切除术,然后进行高血压(定义为连续测量≥2次收缩压≥140mmHg,持续&gt;10分钟)。随机化臂&lt;120 mmHg与140–180 mmHg持续72小时,90天时通过改良Rankin量表的移位分析评估主要结果。在2020年至2022年间前瞻性入选的821名患者是随机的,来源人群来自中国的44家医院。在一个独立的数据和安全监测委员会审查了数据后,出于安全考虑,该试验于2022年6月暂停。出乎意料的是,主要结果是,与强度较低的治疗组相比,强度较高的治疗组更有可能出现更糟糕的结果,早期神经系统恶化和残疾率更高。这项研究再次证明了急性大血管闭塞缺血性卒中后血压与功能结果之间的复杂关系。1这是一项重要的试验,建立在该领域积累的观察数据基础上,并提供了随机试验证据,证明更强烈的降压(<120 mmHg)不仅是中性的,而且是有害的。在这方面,这项研究引起了急诊科和中风中心的广泛关注,因为血压是所有中风患者术后必须管理的参数。然而,在解释结果并将其应用于临床之前,需要注意并全面讨论几点。首先,来自ENCHANTED2/MT试验论文3的图2表明&lt;在最初的3天中,在更强化的治疗组中仅勉强达到120mmHg。尽管当前的指南2推荐&lt;180毫米汞柱,迄今为止尚未确定接受机械血栓切除术的缺血性中风患者的最佳血压目标。1综合来看,医生可能需要根据患者的既往病史和当前血压状况以及闭塞血管再通的成功情况,在机械血栓切除术后采用个性化的收缩压控制靶点。其次,大约75%的急性中风患者的血压升高,并且通常在随后的几天内自发下降。4在ENCHANTED2/MT试验中,强化治疗组有3627名(66%)患者和低强化治疗组的261名(64%)患者患有病前高血压,限制了卒中后结果由病前高血压发生率引起的可能性。自发性脑卒中后高血压可能是缺血性脑卒中的代偿性反应;因此,相对较低的血压可能是更强化治疗组功能较差的部分原因。第三,值得注意的是,两组之间的症状性脑出血率没有差异,这与之前发表的BP-TARGET试验一致,5,其中缺血性中风患者成功再灌注后100–129 mmHg的积极收缩压目标与130–185 mmHg的标准护理收缩压目标相比,在24–36小时时并没有降低脑出血率,这表明在收缩压的这种更密集的治疗水平上缺乏保护,或者在收缩压不太密集的这种治疗水平上对症状性实质内出血转化缺乏危害。为了回答急性大血管闭塞性中风患者机械血栓切除术后的最佳收缩压目标应该是什么的问题,需要正在进行的相关临床试验的结果,以及未来更严格设计的临床试验。袁云鹏:写作——初稿。魏宝珠:写作-原稿:朱文云:写作-初稿。杨柳:写作——初稿。万英峰:写作——原稿。 袁云鹏、魏宝珠、朱文云、杨柳和万英峰声明无利益冲突。不适用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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