Effects of Intensive Blood Pressure Lowering on Brain Swelling in Thrombolyzed Acute Ischemic Stroke: The ENCHANTED Results

Guobin Zhang; Chen Chen; Xinwen Ren; Yang Zhao; Menglu Ouyang; Laurent Billot; Qiang Li; Xia Wang; Luyun Zhang; Sheila Ong; Leibo Liu; Shoujiang You; Richard I Lindley; Thompson G Robinson; Gang Li; Xiaoying Chen; Yi Sui; Craig S Anderson; Lili Song; ENCHANTED Investigators

doi:10.1161/STROKEAHA.124.049938

Effects of Intensive Blood Pressure Lowering on Brain Swelling in Thrombolyzed Acute Ischemic Stroke: The ENCHANTED Results

Stroke. 2025 Jun;56(6):1388-1395. doi: 10.1161/STROKEAHA.124.049938. Epub 2025 Apr 3.

Authors

Guobin Zhang^#^{1

2}, Chen Chen^#^{2

3

4}, Xinwen Ren^#⁴, Yang Zhao^{2

4}, Menglu Ouyang⁴, Laurent Billot⁴, Qiang Li⁴, Xia Wang⁴, Luyun Zhang^{2

5}, Sheila Ong⁴, Leibo Liu⁴, Shoujiang You⁶, Richard I Lindley⁷, Thompson G Robinson⁸, Gang Li³, Xiaoying Chen⁴, Yi Sui⁵, Craig S Anderson^#^{2

4

9

10}, Lili Song^#^{2

4

10}; ENCHANTED Investigators

Collaborators

ENCHANTED Investigators:
M Krause, M Priglinger, S Day, S Jala, L Davies, C Delcourt, C Carcel, A Malavera, E Ray, C S Anderson, T Wijeratne, S Celestino, L Y Law, G Ng, K Nagao, G Weiss, N Titton, C Batista, D Zãn, L Carbonera, K Ferreira, R Castro, R K Martins Filho, M Carvalho, M Libardi, G Martins, D Fagundes, G Baron, A Boehringer, J Barbosa, R Bazan, G Braga, G Luvizutto, P Ribeiro, F Winckler, C Moro, A Longo, R Liberato, R Barbosa, P Magalhães, M Portal, K Martin, A Souza, D Cuervo, D Perin, L Marques, F Oliveira, M Battaglini, F Lourenço, K Ferreira, G Silva, L Duarte, M Alves, J Sousa, M Uhehara, A Brunser, E Mazzón, M Spencer, I Acosta, A Rojo, R Rivas, C Klapp, L Carvallo, P Carvallo, E Mansilla, J Flores, M Alvarado, A Herrera, C Reyes, F Jurado, G Bustamante, L Bravo, J M Matamala, R Guerrero, G Chen, S Zhou, L Ping, W Liu, L Liu, Y Tian, H Xu, J Wang, G Wu, L Wang, Z Zhen, L Wang, J Zhang, M Yan, L Wang, Q Zhang, X Tao, C Liu, Y Cao, J Shi, S You, X Zhang, L Tai, L Xu, H Lu, H Nie, X Li, J Zhou, Y Liu, P Gong, Y Tian, H Zhao, J Zhang, R Li, X Wang, Q Chen, L Wu, J Zhang, L Jia, X Guo, X Li, G Chen, B Lin, W Zhu, K Yang, J Zhang, Z Zhang, C Xie, D Wu, Z Zhang, X Li, Y Wang, D Liu, Z Liu, L Liang, Q Cao, X Zhang, J Xia, X Li, Y Weng, J Li, T Xu, D Geng, X Yan, D Wang, N Zhao, J Li, D Wang, Z Tang, L Wang, W Yin, S Wang, D Wang, W Huang, Y Yang, A Song, Y Hao, A Zhang, B Qiao, J Yang, H Yan, X Wei, Z Tao, H Liu, Y Lv, H Yang, L Han, X Mao, L Ge, Y Zhang, S He, H Zhao, Q Zhang, J Jiang, M Yan, Y Wang, D Liu, W Wu, H Wang, L Yang, G Li, Y Tang, H Sun, F Li, Y Sun, C Geng, L Song, H Zhang, Y Wu, L Huang, Z Zhang, J Zhu, F Zhang, Z Jin, R Zheng, Q Yang, W Zheng, X Zhuang, X Chen, L Li, J Du, Y Lai, Y Zhou, H Duan, Q Cao, E Xu, Q Lin, L Zhan, J Wu, C Wei, X Feng, Q Huang, L Yang, X Liu, J He, B Wang, W Li, P Chen, X Zeng, F Guo, H Dai, Q Su, F Long, B Chen, D Wang, M Dai, H Nie, X Wu, T Wu, B Bao, Y Wang, Y Xu, Y Shao, X Zhang, S Li, F Silva, J A Castellanos, M A Malavera, M Muñoz-Collazos, E Solano, W H T Leung, S Sureshbabu, S Shekhar, S Singla, L Saini, Sunita, M Kate, R Sarvotham, A G William, A Deepak, M Bk, S N Sharma, S K, P Kr, S George, R Benny, V Bolegave, M Basle, S Gore, P George, S Kumaravelu, S Rahamath, P G Raj, A R Devi, A Sharma, J Prajapati, M Parmar, D Patel, T Panchal, S P Gorthi, V Prabhu, A Prabhu, V Chandran, A Chatterjee, R Nair, V K Nambiar, D Ts, S Tp, A V Ajai, S Paul, P C Natarajan, D Chittibabu, N C Borah, M Ghose, N Choudhury, P Gohain, K Kalita, D Duberkar, N Pawar, R Bhaviskar, S Ricci, E Caterbi, S Cenciarelli, R Condurso, E Gallinella, L Greco, C Marando, S Mastrocola, A Mattioni, E Sacchini, I Sicilia, A Gallina, D Giannandrea, E Marsili, T Mazzoli, C Padiglioni, F Corea, A Guidubaldi, S Micheli, M Barbi, J Kim, H J Song, H S Jeong, J G Lim, S M Park, K B Lee, H W Hwang, J S Kim, S U Kwon, D W Kang, Y J Kim, B J Kim, J M Park, K Kang, B Kim, O Kwon, J J Lee, Y W Kim, Y H Hwang, H S Kwon, J Koo, K Lee, T Kim, A Ahn, J H Rha, H K Park, C W Yoon, B Chan, H L Teoh, P Paliwal, L Y J Wong, J T Chen, V K Sharma, D A De Silva, H M Chang, N Fabiaña, J Marti, R Delgado, A Martínez, L Prats, P Camps, C W Liou, T Y Tan, C F Liu, H H Cheng, H L Po, Y J Lin, C L Chou, C H Lin, C C Yen, Y T Chang, Y T Hsu, J D Lee, M Lee, Y C Huang, Y C Huang, C Y Wu, N C Suwanwela, A Chutinet, Y Likitjaroen, D Roongpiboonsopit, S Charnwut, A Dyker, M Hossain, G K Muddegowda, R Sanyal, C Roffe, I Natarajan, K Finney, L Sztriha, J Teo, F K Chan, J Lim, B Chitando, B Clarke, B Patel, U Khan, R Ghatala, S Trippier, L Kalra, D Manawadu, N Sikondari, J Aeron-Thomas, W Sunman, G Wilkes, C Richardson, A Buch, B Jackson, O Halse, S Mashate, P Wilding, V Nguyen, K Rashed, M R Qadiri, S Board, C Buckley, C Smith, M James, S Keenan, A Bouring, T England, R Donnelly, J Scott, M Maddula, J Beavan, R Perry, N Francia, C Watchhurst, A Banaras, A Ashton, A Mistri, K Musarrat, L Manning, T Robinson, D Eveson, J Kallingal, J Perez, L Harrison, T Marsden, M J Macleod, J Furnace, R Clarke, J Reid, E Warburton, J Mitchell, D Day, N Church, E Amis, C Price, H Rodgers, R Whiting, M Hussain, M Harvey, S Brown, J Foot, D Tryambake, D Broughton, A Bergin, A Annamalai, L Dixon, N Weir, C Blank, K Harkness, A Ali, E Richards, K Stocks, D W Bruce, M Wani, T Anjum, M Krishnan, T Nguyen Huy, A Truong Le Tuan, L Dam Thi Cam, T Ngo Thi Kim, B Pham Nguyen, A Nguyen Dat, C Nguyen Van, T Mai Duy, P Dao Viet, D Nguyen Tien, T Vo Van, K Le Kim, T Bui Ngoc, T Tran Le Thanh, S Nguyen Hoanh, S Pham Phuoc, T Tran Van, B Doan Thi, H Nguyen Thi Thu, M Nguyen Duy, D Ngo Van

Affiliations

¹ Department of Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China (G.Z.).
² The George Institute for Global Health China, Beijing (G.Z., C.C., Y.Z., L.Z., C.S.A., L.S.).
³ Neurology Department, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China (C.C., G.L.).
⁴ The George Institute for Global Health, University of New South Wales, Sydney, Australia (C.C., X.R., Y.Z., M.O., L.B., Q.L., X.W., S.O., L.L., X.C., C.S.A., L.S.).
⁵ Shenyang First People's Hospital, Shenyang Brain Hospital, Shenyang Brain Institute, China (L.Z., Y.S.).
⁶ Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China (S.Y.).
⁷ University of Sydney, Australia (R.I.L.).
⁸ Department of Cardiovascular Sciences and National Institute of Health and Care Research Leicester Biomedical Research Centre, United Kingdom (T.G.R.).
⁹ Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile (C.S.A.).
¹⁰ The Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China (C.S.A., L.S.).

^# Contributed equally.

PMID: 40177745
DOI: 10.1161/STROKEAHA.124.049938

Abstract

Background: Cerebral swelling in relation to cytotoxic edema is a predictor of poor outcome in acute ischemic stroke (AIS) and elevated blood pressure (BP) promotes its development. Whether intensive BP-lowering treatment reduces cerebral swelling is uncertain. We aimed to determine whether intensive BP lowering reduces the severity of cerebral swelling after thrombolysis for AIS.

Methods: A secondary analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial factorial, international, multicenter, open-label, blinded end point, randomized controlled trial of alteplase dose and levels of BP control in thrombolyzed patients with AIS. Participants were randomly assigned to intensive (systolic target 130-140 mm Hg within 1 hour; maintained for 72 hours) or guideline-recommended (systolic target <180 mm Hg) BP management. Available serial brain images (baseline and follow-up, computed tomography, or magnetic resonance imaging) were centrally analyzed with standardized techniques (Apollo MIStar software) by expert readers blind to clinical details to rate swelling severity (from 0 no to 6 most severe swelling [midline shift and effacement of basal cisterns]) and other abnormalities. Primary outcome was any cerebral swelling (score, 1-6) in logistic regression models.

Results: Of 1477/2196 (67.3%) patients (mean age, 67.7 years; female, 39.6%) with sequential scans, the between-group mean systolic BP difference was 6.6 mm Hg over 24 hours. No significant difference was found in the treatment effect on any cerebral swelling between intensive and guideline-recommended BP management (22.12% versus 22.39%, adjusted odds ratio, 1.05 [95% CI, 0.81-1.36]; P=0.71). Results were consistent across different groups of swelling severity (swelling score 2-6, 3-6, and 4-6; and ordinal shift on swelling score).

Conclusions: Modest early intensive BP lowering does not seem to alter cerebral swelling in thrombolyzed patients with AIS. Further research is needed to quantify brain edema to allow a better understanding of the complex relations of BP and outcomes from AIS.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616.

Keywords: blood pressure; brain edema; clinical trial; ischemic stroke; thrombolytic therapy.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Aged
Antihypertensive Agents* / administration & dosage
Antihypertensive Agents* / therapeutic use
Blood Pressure* / drug effects
Brain Edema* / diagnostic imaging
Brain Edema* / drug therapy
Brain Edema* / etiology
Female
Fibrinolytic Agents* / therapeutic use
Humans
Hypertension / drug therapy
Ischemic Stroke* / complications
Ischemic Stroke* / diagnostic imaging
Ischemic Stroke* / drug therapy
Male
Middle Aged
Thrombolytic Therapy* / adverse effects
Tissue Plasminogen Activator* / administration & dosage
Tissue Plasminogen Activator* / therapeutic use
Treatment Outcome

Substances

Antihypertensive Agents
Fibrinolytic Agents
Tissue Plasminogen Activator

Associated data

ClinicalTrials.gov/NCT01422616