TY - JOUR
T1 - Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT)
T2 - a multicentre, open-label, blinded-endpoint, randomised controlled trial
AU - Yang, Pengfei
AU - Song, Lili
AU - Zhang, Yongwei
AU - Zhang, Xiaoxi
AU - Chen, Xiaoying
AU - Li, Yunke
AU - Sun, Lingli
AU - Wan, Yingfeng
AU - Billot, Laurent
AU - Li, Qiang
AU - Ren, Xinwen
AU - Shen, Hongjian
AU - Zhang, Lei
AU - Li, Zifu
AU - Xing, Pengfei
AU - Zhang, Yongxin
AU - Zhang, Ping
AU - Hua, Weilong
AU - Shen, Fang
AU - Zhou, Yihan
AU - Tian, Bing
AU - Chen, Wenhuo
AU - Han, Hongxing
AU - Zhang, Liyong
AU - Xu, Chenghua
AU - Li, Tong
AU - Peng, Ya
AU - Yue, Xincan
AU - Chen, Shengli
AU - Wen, Changming
AU - Wan, Shu
AU - Yin, Congguo
AU - Wei, Ming
AU - Shu, Hansheng
AU - Nan, Guangxian
AU - Liu, Sheng
AU - Liu, Wenhua
AU - Cai, Yiling
AU - Sui, Yi
AU - Chen, Maohua
AU - Zhou, Yu
AU - Zuo, Qiao
AU - Dai, Dongwei
AU - Zhao, Rui
AU - Huang, Qinghai
AU - Xu, Yi
AU - Deng, Benqiang
AU - Wu, Tao
AU - Roos, Yvo
AU - ENCHANTED2/MT Investigators
AU - Majoie, Charles
N1 - Funding Information: The study is supported by grants from the Shanghai Hospital Development Center (SHDC2020CR6014), the NHMRC (APP1149987), China Stroke Prevention Project (GN-2020 R0008), Shanghai Changhai Hospital (2019YXK034), Science and Technology Commission of Shanghai Municipality (22Y31900400), Takeda China, Genesis Medtech (Shanghai), and Penumbra. The Australian MRFF Clinical Trials Activity Initiative (APP2015371) was awarded in 2022 for conduct of the trial in Australia between 2022 and 2025. Hasten Biopharmaceutic will provide funding instead of Takeda China for conduct of the trial between 2022 and 2025. The research team acknowledges the support of iSchemaView for providing a free RAPID software licence for the study in China, and the EuroQol Group for use of the EQ-5D-3L. CSA is a Senior Investigator Fellow for the NHMRC. We thank the investigators and research staff at the participating sites of the various participating emergency departments, intensive care units, stroke units, and neurointervention departments (appendix pp 6–7), members of the trial steering, advisory, data and safety monitoring board, events and imaging adjudication, and medical review committees (appendix pp 4–5), and executive staff at The George Institute for Global Health China for their support of the study. We also thank the participants, their relatives, and their families. Funding Information: The study is supported by grants from the Shanghai Hospital Development Center (SHDC2020CR6014), the NHMRC (APP1149987), China Stroke Prevention Project (GN-2020 R0008), Shanghai Changhai Hospital (2019YXK034), Science and Technology Commission of Shanghai Municipality (22Y31900400), Takeda China, Genesis Medtech (Shanghai), and Penumbra. The Australian MRFF Clinical Trials Activity Initiative (APP2015371) was awarded in 2022 for conduct of the trial in Australia between 2022 and 2025. Hasten Biopharmaceutic will provide funding instead of Takeda China for conduct of the trial between 2022 and 2025. The research team acknowledges the support of iSchemaView for providing a free RAPID software licence for the study in China, and the EuroQol Group for use of the EQ-5D-3L. CSA is a Senior Investigator Fellow for the NHMRC. We thank the investigators and research staff at the participating sites of the various participating emergency departments, intensive care units, stroke units, and neurointervention departments (appendix pp 6–7), members of the trial steering, advisory, data and safety monitoring board, events and imaging adjudication, and medical review committees (appendix pp 4–5), and executive staff at The George Institute for Global Health China for their support of the study. We also thank the participants, their relatives, and their families. Publisher Copyright: © 2022 Elsevier Ltd
PY - 2022/11/5
Y1 - 2022/11/5
N2 - Background: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. Methods: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140–180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. Findings: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07–1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18–1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47–2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. Interpretation: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. Funding: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.
AB - Background: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. Methods: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140–180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. Findings: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07–1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18–1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47–2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. Interpretation: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. Funding: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.
UR - http://www.scopus.com/inward/record.url?scp=85141258853&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S0140-6736(22)01882-7
DO - https://doi.org/10.1016/S0140-6736(22)01882-7
M3 - Article
C2 - 36341753
SN - 0140-6736
VL - 400
SP - 1585
EP - 1596
JO - The Lancet
JF - The Lancet
IS - 10363
ER -