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Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial

Chen, Chen; Ouyang, Menglu; Ong, Sheila; Zhang, Luyun; Zhang, Guobin; Delcourt, Candice; Mair, Grant; Liu, Leibo; Billot, Laurent; Li, Qiang; Chen, Xiaoying; Parsons, Mark; Broderick, Joseph P.; Demchuk, Andrew M.; Bath, Philip M.; Donnan, Geoffrey A.; Levi, Christopher; Chalmers, John; Lindley, Richard I.; Martins, Sheila O.; Pontes-Neto, Octavio M.; Venturelli, Paula Muñoz; Olavarría, Verónica; Lavados, Pablo; Robinson, Thompson G.; Wardlaw, Joanna M.; Li, Gang; Wang, Xia; Song, Lili; Anderson, Craig S.; ENCHANTED investigators


Chen Chen

Menglu Ouyang

Sheila Ong

Luyun Zhang

Guobin Zhang

Candice Delcourt

Grant Mair

Leibo Liu

Laurent Billot

Qiang Li

Xiaoying Chen

Mark Parsons

Joseph P. Broderick

Andrew M. Demchuk

Stroke Association Professor of Stroke Medicine

Geoffrey A. Donnan

Christopher Levi

John Chalmers

Richard I. Lindley

Sheila O. Martins

Octavio M. Pontes-Neto

Paula Muñoz Venturelli

Verónica Olavarría

Pablo Lavados

Thompson G. Robinson

Joanna M. Wardlaw

Gang Li

Xia Wang

Lili Song

Craig S. Anderson

ENCHANTED investigators


Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130–140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target <180 mm Hg) blood pressure management in patients with hypertension (systolic blood pressure >150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018. Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24–36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with, number NCT01422616. Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24–36 h. Mean achieved systolic blood pressures over 1–24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24–36 h (0.3 [IQR 0.0–16.6] in the intensive group and 0.9 [0.0–12.5] in the guideline group; log Δmean −0.17, 95% CI −0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Interpretation: Intensive blood pressure lowering treatment to a systolic target <140 mm Hg within several hours after the onset of symptoms may not increase the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke of mild to moderate neurological severity. Funding: National Health and Medical Research Council of Australia; UK Stroke Association; UK Dementia Research Institute; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.


Chen, C., Ouyang, M., Ong, S., Zhang, L., Zhang, G., Delcourt, C., …ENCHANTED investigators. (2023). Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial. EClinicalMedicine, 57, Article 101849.

Journal Article Type Article
Acceptance Date Jan 12, 2023
Online Publication Date Feb 14, 2023
Publication Date 2023-03
Deposit Date Jan 13, 2023
Publicly Available Date Feb 14, 2023
Journal eClinicalMedicine
Electronic ISSN 2589-5370
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 57
Article Number 101849
Public URL
Publisher URL
Additional Information Authors on behalf of the ENCHANTED investigators


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