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Randomized Controlled Trial
. 2023 Oct 9:383:e076448.
doi: 10.1136/bmj-2023-076448.

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

Liping Liu  1   2 , Xuewei Xie  1   2 , Yuesong Pan  1   2 , Aili Wang  3 , Yufei Wei  1   2 , Jingyi Liu  1   2 , Ximing Nie  1   2 , Dacheng Liu  4 , Zilin Zhao  1   2 , Penglian Wang  1   2 , Suwen Shen  3   5 , Chongke Zhong  3 , Tan Xu  3 , Dali Wang  6 , Gui-Chun Wang  7 , Denghua Song  8 , Yunsheng Ma  9 , Jinguo Zhao  10 , Yong Jiang  1   2 , Jing Jing  1   2 , Xia Meng  1   2 , Katherine Obst  11   12 , Chung-Shiuan Chen  11   12 , David Wang  13 , Yilong Wang  1   2 , Yonghong Zhang  3 , Yongjun Wang  1   2   14   15 , Jiang He  16   12 ; CATIS-2 Investigators
Affiliations
Randomized Controlled Trial

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

Liping Liu et al. BMJ. .

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Ministry of Science and Technology of China, Capital Medical University, Soochow University, Tulane University, the Chinese Stroke Association, the Beijing Municipal Science and Technology Commission, the Changzhou Pharmaceutical Factory, Cspc Ouyi Pharmaceutical Import and Export Trade Co, and Shenzhen Kangzhe Pharmaceutical Co, for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Recruitment, randomisation, and follow-up in a trial of early versus delayed antihypertensive treatment in patients with acute ischaemic stroke. Clinical contraindications (n=4520) included history of atrial fibrillation (n=703), NIH stroke scale score ≥21 (n=101) at baseline assessment, modified Rankin score ≥3 at baseline assessment (n=432), severe heart failure defined as ejection fraction <35% (n=113), kidney failure defined as estimated glomerular filtration rate <20 mL/min/1.73 m2 (n=138), intravenous thrombolytic treatment or mechanical thrombectomy (n=1105), all cause dementia (n=47), mental disorders (n=33), history of cancer (n=133) or other conditions (n=1715)
Fig 2
Fig 2
Mean systolic and diastolic blood pressure since randomisation in a trial of early vs delayed antihypertensive treatment in patients with acute ischaemic stroke. Three blood pressure measurements were obtained every three hours for the first 24 h and then every eight hours during hospital admission until day 14 or hospital discharge. Additionally, three blood pressure measurements were obtained at 21 day and 90 day follow-up visits in all patients. Error bars represent 95% confidence intervals. Tinted regions indicate the timeframe from day 0 to 7
Fig 3
Fig 3
Forest plot of the primary outcome according to subgroups in a trial of early versus delayed antihypertensive treatment in patients with acute ischaemic stroke. The dashed vertical line represents the odds ratio for the overall study population. The box sizes are proportional to the precision of the estimates (with larger boxes indicating a greater degree of precision). CI=confidence interval
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