Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke: multicentre, open label, randomised, controlled trial

Authors

Liping Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Xuewei Xie, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Yuesong Pan, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Aili Wang, Department of Epidemiology, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
Yufei Wei, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Jingyi Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Ximing Nie, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Dacheng Liu, Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Zilin Zhao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Penglian Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Suwen Shen, Department of Epidemiology, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
Chongke Zhong, Department of Epidemiology, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
Tan Xu, Department of Epidemiology, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
Dali Wang, Affiliated Hospital of North China University of Science and Technology, Tang-shan, China.
Gui-Chun Wang, Changtu County Hospital, Tieling, China.
Denghua Song, Sinopharm Tongmei General Hospital, Datong, China.
Yunsheng Ma, The First People's Hospital of Keerqin District, Tongliao, China.
Jinguo Zhao, Weihai Wendeng District People' Hospital, Weihai, China.
Yong Jiang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Jing Jing, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Xia Meng, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Katherine Obst, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Chung-Shiuan Chen, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
David Wang, Neurovascular Division, Department of Neurology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.Follow
Yilong Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Yonghong Zhang, Department of Epidemiology, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
Yongjun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Jiang He, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA jhe@tulane.edu.

Document Type

Article

Abstract

OBJECTIVES: To compared the effect of early antihypertensive treatment started within 24-48 h of stroke onset versus delaying treatment until day eight on reducing dependency or death. DESIGN: Multicentre, randomised, open label trial. SETTING: 106 hospitals in China between 13 June 2018 and 10 July 2022. PARTICIPANTS: 4810 patients (≥40 years) were enrolled with acute ischaemic stroke within 24-48 h of symptom onset and elevated systolic blood pressure between 140 mm Hg and <220 mm Hg. INTERVENTIONS: Patients were randomly assigned to receive antihypertensive treatment immediately after randomisation (aimed at reducing systolic blood pressure by 10%-20% within the first 24 h and a mean blood pressure <140/90 mm Hg within seven days) or to discontinue antihypertensive medications for seven days if they were taking them, and then receive treatment on day 8 (aimed at achieving mean blood pressure <140/90 mm Hg). MAIN OUTCOME MEASURES: The primary outcome was the combination of functional dependency or death (modified Rankin scale score ≥3) at 90 days. Intention to treat analyses were conducted. RESULTS: 2413 patients were assigned to the early treatment group and 2397 were assigned to the delayed treatment group. Mean systolic blood pressure was reduced by 9.7% (from 162.9 mm Hg to 146.4 mm Hg) in the early treatment group and by 4.9% (from 162.8 mm Hg to 154.3 mm Hg) in the delayed treatment group within 24 h after randomisation (P for group difference <0.001). Mean systolic blood pressure was 139.1 mm Hg in the early treatment group and 150.9 mm Hg in the delayed treatment group on day seven (P for group difference <0.001). Additionally, 54.6% of patients in the early treatment group and 22.4% in the delayed treatment group had blood pressure of less than 140/90 mm Hg (P<0.001 for group difference) on day seven. At day 90, 289 trial participants (12.0%) in the early treatment group, compared with 250 (10.5%) in the delayed treatment group, had died or experienced a dependency (odds ratio 1.18 (95% confidence interval 0.98 to 1.41), P=0.08). No significant differences in recurrent stroke or adverse events were reported between the two groups. CONCLUSIONS: Among patients with mild-to-moderate acute ischaemic stroke and systolic blood pressure between 140 mm Hg and <220 mm Hg who did not receive intravenous thrombolytic treatment, early antihypertensive treatment did not reduce the odds of dependency or death at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03479554.

Medical Subject Headings

Humans; Antihypertensive Agents; Stroke (complications, drug therapy); Hypertension (complications, drug therapy); Brain Ischemia (complications, drug therapy); Treatment Outcome; Blood Pressure; Ischemic Stroke; Hypotension

Publication Date

10-9-2023

Publication Title

BMJ (Clinical research ed.)

E-ISSN

1756-1833

Volume

383

First Page

e076448

PubMed ID

37813418

Digital Object Identifier (DOI)

10.1136/bmj-2023-076448

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