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

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

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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 ClinicalTrials.gov, 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.

Original languageEnglish
Article number 101849
Number of pages10
Early online date15 Feb 2023
Publication statusPublished - Mar 2023
Externally publishedYes


  • Acute ischaemic stroke
  • Blood pressure
  • Brain imaging
  • Cerebral infarction
  • Clinical trial
  • Thrombolysis


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