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

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.
Competing Interests: GM received a research grant from the UK Stroke Association, and consulting fee and honoraria from Canon Medical. JB has received consulting fees from Roche, and honoraria on the Executive Committee for TIMELESS Trial from Genentech. AMD received grants from Medtronic and Circle CVI, and has received consulting fees and honoraria from HLS Therapeutics, Hoffmann LaRoche Servier, Astra Zeneca, and Boehringer Ingelheim. He is also a member on Data Safety and Monitoring Boards (DSMB) for Philips and Lumosa, and has a role on the Canadian Stroke Consortium and Canadian Partnership for Stroke Recovery. PB has received research grants from the UK Stroke Association, British Heart Foundation, NIHR HTA, and NUH Charity, and honoraria for advisory board activities from DiaMedica, Phagenesis, and Roche. He is also the Chair and Co-Chair of DSMBs for ESPS-2 and AVERT-Dose, respectively, and has stock from DiaMedica. AMD has stock from Circle CVI. RIL has received grants from the National Health and Medical Research Council (NHMRC). JC reports receiving a Program Grant the NHMRC from of Australia and is the Chair of the Steering Committee for ENCHANTED. SM has received grants from Ministry of Health PROADI SUS Hospital Moinhos de Vento, including RESILIENT Direct TNK, RESILIENT Extend IV, TRIDENT, and PROMOTE trials. She also received honoraria from Boehringer Ingelheim, Medtronic, Penumbra, Novartis, Novo Nordisk, Pfizer, Bayer, Servier, and Daiichi Sankyo, has participated on a DSMB for Johnson and Johnson's Executive Board for the Librexia clinical trial, and is the President of World Stroke Organisation and Brazilian Stroke Network. PMV has received a research grant from ANID Fondecyt Regular, Chile, and is member of the Scientific Advisors Committee to the Chilean Ministry of Sciences and Technology, for the COVID-19 vaccine national strategy. VVO has received a research grant from ANID Fondecyt Regular 1,181,333 Chile and a research grant from Boehringer Ingelheim. PL has received a research grant from ANID Fondecyt Regular, Chile, and honoraria from Boehringer Ingelheim, and has a role on a DSMB for Boehringer Ingelheim and the Chilean Ministry of Health, and is the President of the Chilean Stroke Association. CSA and LS received research grants from the NHMRC, MRC, Takeda China, and Penumbra. The other authors declare no competing interests.
(© 2023 The Author(s).)