Impact of Ultra-Early Perioperative Antihypertensive Therapy in Acute Intracerebral Hemorrhage
Journal
Stroke
ISSN
0039-2499
Date Issued
2026-06
Author(s)
Tao Liu
Linan Chen
Leibo Liu
Yang Liu
Lu Ma
Laurent Billot
Qiang Li
Zhihao Zhao
Alejandra Malavera
Asita de Silva
Huy Thang Nguyen
Kolawole W. Wahab
Jeyaraj D. Pandian
Antonio Arauz
Mohammad Wasay
Octavio M. Pontes-Neto
Rongcai Jiang
Carlos Abanto
Lili Song
Chao You
Craig S. Anderson
Xin Hu
Xiaoying Chen
Type
journal-article
Abstract
<jats:sec>
<jats:title>BACKGROUND:</jats:title>
<jats:p>Early intensive blood pressure (BP) lowering improves outcomes in acute intracerebral hemorrhage, but its perioperative benefit among patients undergoing surgical hematoma evacuation is uncertain. We evaluated whether earlier achievement of intensive BP targets is associated with improved outcomes in this population.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>METHODS:</jats:title>
<jats:p>Post hoc secondary analysis of the INTERACT3 (the third Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial) pragmatic, international, multicenter, blinded-end point, and stepped-wedge cluster-randomized trial. Among 7036 enrolled intracerebral hemorrhage patients at 121 hospitals, those who underwent surgical hematoma evacuation were included. Patients were categorized by time from hospital arrival to achieving the target systolic BP <140 mm Hg: ≤2 hours versus >2 hours. The primary outcome was 6-month mortality. Key secondary outcomes included death or disability (modified Rankin Scale scores 4–6), modified Rankin Scale score shift, health-related quality-of-life (EuroQol 5-Dimension 3-Level [EQ-5D-3L] domains, visual analog scale, and health utility index), and serious adverse events. Adjusted associations were estimated using Cox, logistic, ordinal logistic, and linear regression models, controlling for age, sex, treatment type, and admission Glasgow Coma Scale.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESULTS:</jats:title>
<jats:p>
Of 7036 patients with acute intracerebral hemorrhage, 1506 underwent surgical hematoma evacuation (mean [SD] age, 59.7 [11.8] years; 33.9% women). Overall, there was no statistically significant difference in 6-month mortality between patients who achieved target BP within 2 hours of treatment initiation and those who achieved it after 2 hours (adjusted hazard ratio, 0.81 [95% CI, 0.63–1.04];
<jats:italic toggle="yes">P</jats:italic>
=0.09). Early BP achievement was associated with a lower risk of death or disability (adjusted odds ratio [OR], 0.71 [95% CI, 0.56–0.90];
<jats:italic toggle="yes">P</jats:italic>
=0.01), a favorable shift in the distribution of modified Rankin Scale scores (adjusted common OR, 0.73 [95% CI, 0.60–0.89];
<jats:italic toggle="yes">P</jats:italic>
<0.01), and fewer serious adverse events (adjusted OR, 0.73 [95% CI, 0.57–0.94];
<jats:italic toggle="yes">P</jats:italic>
=0.02). EuroQol 5-Dimension 3-Level outcomes also favored the early group, with significant improvements in mobility (adjusted OR, 0.76 [95% CI, 0.60–0.97];
<jats:italic toggle="yes">P</jats:italic>
=0.03), pain/discomfort (adjusted OR, 0.72 [95% CI, 0.54–0.95];
<jats:italic toggle="yes">P</jats:italic>
=0.02), and usual activities (adjusted OR, 0.79 [95% CI, 0.62–1.00];
<jats:italic toggle="yes">P</jats:italic>
=0.05), as well as higher visual analog scale (mean difference, 0.08 [95% CI, 0.002–0.17];
<jats:italic toggle="yes">P</jats:italic>
=0.04) and health utility scores (mean difference, 0.05 [95% CI, 0.02–0.09];
<jats:italic toggle="yes">P</jats:italic>
<0.01).
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>CONCLUSIONS:</jats:title>
<jats:p>In patients with intracerebral hemorrhage undergoing surgical hematoma evacuation, perioperative intensive BP reduction appears safe. Achieving systolic BP <140 mm Hg within 2 hours was associated with better functional and quality-of-life outcomes, and fewer serious adverse events. These time-sensitive associations support prioritizing ultra-early perioperative BP control; confirmatory prospective analyses are warranted.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>REGISTRATION:</jats:title>
<jats:p>
URL:
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</jats:ext-link>
; Unique identifier: NCT03209258.
</jats:p>
</jats:sec>
<jats:title>BACKGROUND:</jats:title>
<jats:p>Early intensive blood pressure (BP) lowering improves outcomes in acute intracerebral hemorrhage, but its perioperative benefit among patients undergoing surgical hematoma evacuation is uncertain. We evaluated whether earlier achievement of intensive BP targets is associated with improved outcomes in this population.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>METHODS:</jats:title>
<jats:p>Post hoc secondary analysis of the INTERACT3 (the third Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial) pragmatic, international, multicenter, blinded-end point, and stepped-wedge cluster-randomized trial. Among 7036 enrolled intracerebral hemorrhage patients at 121 hospitals, those who underwent surgical hematoma evacuation were included. Patients were categorized by time from hospital arrival to achieving the target systolic BP <140 mm Hg: ≤2 hours versus >2 hours. The primary outcome was 6-month mortality. Key secondary outcomes included death or disability (modified Rankin Scale scores 4–6), modified Rankin Scale score shift, health-related quality-of-life (EuroQol 5-Dimension 3-Level [EQ-5D-3L] domains, visual analog scale, and health utility index), and serious adverse events. Adjusted associations were estimated using Cox, logistic, ordinal logistic, and linear regression models, controlling for age, sex, treatment type, and admission Glasgow Coma Scale.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESULTS:</jats:title>
<jats:p>
Of 7036 patients with acute intracerebral hemorrhage, 1506 underwent surgical hematoma evacuation (mean [SD] age, 59.7 [11.8] years; 33.9% women). Overall, there was no statistically significant difference in 6-month mortality between patients who achieved target BP within 2 hours of treatment initiation and those who achieved it after 2 hours (adjusted hazard ratio, 0.81 [95% CI, 0.63–1.04];
<jats:italic toggle="yes">P</jats:italic>
=0.09). Early BP achievement was associated with a lower risk of death or disability (adjusted odds ratio [OR], 0.71 [95% CI, 0.56–0.90];
<jats:italic toggle="yes">P</jats:italic>
=0.01), a favorable shift in the distribution of modified Rankin Scale scores (adjusted common OR, 0.73 [95% CI, 0.60–0.89];
<jats:italic toggle="yes">P</jats:italic>
<0.01), and fewer serious adverse events (adjusted OR, 0.73 [95% CI, 0.57–0.94];
<jats:italic toggle="yes">P</jats:italic>
=0.02). EuroQol 5-Dimension 3-Level outcomes also favored the early group, with significant improvements in mobility (adjusted OR, 0.76 [95% CI, 0.60–0.97];
<jats:italic toggle="yes">P</jats:italic>
=0.03), pain/discomfort (adjusted OR, 0.72 [95% CI, 0.54–0.95];
<jats:italic toggle="yes">P</jats:italic>
=0.02), and usual activities (adjusted OR, 0.79 [95% CI, 0.62–1.00];
<jats:italic toggle="yes">P</jats:italic>
=0.05), as well as higher visual analog scale (mean difference, 0.08 [95% CI, 0.002–0.17];
<jats:italic toggle="yes">P</jats:italic>
=0.04) and health utility scores (mean difference, 0.05 [95% CI, 0.02–0.09];
<jats:italic toggle="yes">P</jats:italic>
<0.01).
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>CONCLUSIONS:</jats:title>
<jats:p>In patients with intracerebral hemorrhage undergoing surgical hematoma evacuation, perioperative intensive BP reduction appears safe. Achieving systolic BP <140 mm Hg within 2 hours was associated with better functional and quality-of-life outcomes, and fewer serious adverse events. These time-sensitive associations support prioritizing ultra-early perioperative BP control; confirmatory prospective analyses are warranted.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>REGISTRATION:</jats:title>
<jats:p>
URL:
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</jats:ext-link>
; Unique identifier: NCT03209258.
</jats:p>
</jats:sec>