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Impact of Ultra-Early Perioperative Antihypertensive Therapy in Acute Intracerebral Hemorrhage
(Ovid Technologies (Wolters Kluwer Health), 2026-06)
Tao Liu
;
Linan Chen
;
Leibo Liu
;
Yang Liu
;
Lu Ma
<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>
1
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Effects of Blood Pressure Lowering Across Hematoma Volume in Acute Intracerebral Hemorrhage: Pooled Analysis of the Four
<scp>INTERACT</scp>
and
<scp>ATACH</scp>
‐2 Trials
(Wiley, 2026-04-01)
Xinwen Ren
;
Qiang Li
;
Menglu Ouyang
;
Xiaoying Chen
;
Chen Chen
<jats:sec> <jats:title>Objective</jats:title> <jats:p>The objective of this study was to assess the heterogeneity in treatment effect of intensive blood pressure (BP)‐lowering across hematoma volume after acute intracerebral hemorrhage (ICH).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We undertook a pooled analysis of individual patient data from the pivotal trials of early intensive BP‐lowering in ICH (the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 4 [INTERACT4] and Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 [ATACH‐2] studies). The primary outcome was functional recovery, defined by the distribution of scores on modified Rankin scale (mRS). Secondary outcomes were hematoma expansion (HE) over 24 hours, defined by absolute (<0, 0–6, 6–12.5, and >12.5 ml) and relative HE (<0, 0–33, 33–66, and >66%). Generalized linear mixed models with trial as a random effect were conducted. We further assessed effect modification by hematoma volume and plotted the treatment effect curve.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> Among 6,125 individuals with available hematoma volume, intensive BP‐lowering improved functional recovery (odds ratio [OR] for unfavorable shift in mRS score = 0.90, 95% confidence interval [CI] = 0.82 to 0.99, <jats:italic>p</jats:italic> = 0.027). In 3,897 participants with available HE, intensive BP‐lowering reduced the risk of absolute (OR = 0.88, 95% CI = 0.78 to 0.99, <jats:italic>p</jats:italic> = 0.043) and relative (OR = 0.88, 95% CI = 0.78 to 0.99, <jats:italic>p</jats:italic> = 0.034) HE. We found effect modification of treatment on functional outcome and absolute HE by hematoma volume (p for interaction = 0.043 and 0.025, respectively). U‐shaped curves were observed, with benefits seen in cases with hematoma volume of 7.5 to 27.5 and 7.0 to 32.5 ml, respectively, both peaking at 20 ml. </jats:p> </jats:sec> <jats:sec> <jats:title>Interpretation</jats:title> <jats:p>Early intensive BP‐lowering improves functional outcome and reduces HE in ICH. Heterogeneity by hematoma volume indicates the importance of patient selection in future trials and clinical practice. ANN NEUROL 2026</jats:p> </jats:sec>
1
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Systolic Blood Pressure Trajectory and Outcomes in Acute Intracerebral Hemorrhage
(Ovid Technologies (Wolters Kluwer Health), 2026-04-14)
Xia Wang
;
Thanh G. Phan
;
Xinwen Ren
;
Henry H. Ma
;
Qiang Li
1
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Sex differences in the clinical and surgical management after intracerebral hemorrhage: A post hoc analysis of the INTERACT3 clinical trial
(SAGE Publications, 2026-02-05)
Ma. Ignacia Allende
;
Cheryl Carcel
;
MUÑOZ VENTURELLI, PAULA ANDREA
;
Katie Harris
;
Menglu Ouyang
<jats:sec> <jats:title>Introduction:</jats:title> <jats:p>As the management of intracerebral hemorrhage (ICH) shifts from historical inertia to more proactive, evidence-based care, ensuring sex-equitable access to best-practice stroke care is increasingly important. Data on sex differences in access to care for ICH remains limited and often conflicting. More robust evidence is required to understand where disparities may exist to inform targeted interventions.</jats:p> </jats:sec> <jats:sec> <jats:title>Aims:</jats:title> <jats:p>We aimed to determine sex differences in the clinical and surgical management of patients with acute ICH who participated in the third Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>We performed a post hoc analysis of INTERACT3, an international stepped-wedge, cluster-randomised trial undertaken in 121 hospitals across 9 low- to middle-income countries and 1 high-income country. The trial aimed to evaluate a care bundle composed of intensive blood-pressure lowering, rapid correction of hyperglycemia, fever control, and reversal of anticoagulation; in adults presenting within 6 h of ICH onset. We used mixed-effects logistic regression to evaluate sex differences in access to surgical interventions, admission to an intensive care unit or acute stroke unit, assisted feeding, physiotherapy, occupational therapy, withdrawal of care, and use of pharmacological therapies (antiepileptic drugs, mannitol, dexamethasone, and statins). Patterns of care were further evaluated using latent class analysis, with sex differences analyzed using the same regression framework.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Of 7036 patients with ICH, 2533 (36%) were female. Females were older and had more severe neurological deficits. Overall care provision was similar across sexes. However, females were more likely to receive assisted feeding (odds ratio [OR] 1.15, 95% CI = 1.02–1.31), and were less likely to withdraw from active care (OR 0.41, 95% CI = 0.19–0.87) than males. Surgical interventions were accessed at similar rates among sexes, a finding that persisted in analyses restricted to supratentorial ICH with hematoma volumes ⩾ 30 mL. Three distinct care classes were identified: high-intensity, high-rehabilitation, and low-intensity, with females and males having comparable distributions within the classes.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Following acute ICH, females generally receive similar active acute care interventions as males, except for observed differences in access to assisted feeding and decision to withdraw from active care. These findings suggest that equal access to ICH interventions for females and males is feasible and exists in some settings. However, disparities in certain key interventions remain and present actionable opportunities for improvement. Further research is needed to explore not only access but also the timing and frequency of these interventions.</jats:p> </jats:sec> <jats:sec> <jats:title>Data access statement:</jats:title> <jats:p>Individual, de-identified participant data used in these analyses will be shared on request from any qualified investigator after the approval of a protocol and signed data access agreement via both the trial steering committee and the research office of The George Institute for Global Health (Sydney, NSW, Australia).</jats:p> </jats:sec>
1
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Low-Intensity Monitoring for Mild-to-Moderate Acute Ischemic Stroke Is Cost Saving: Economic Evaluation for OPTIMISTmain
(Ovid Technologies (Wolters Kluwer Health), 2026-03)
Lizheng Xu
;
Menglu Ouyang
;
Emily R. Atkins
;
Debbie Summers
;
Yi Sui
<jats:sec> <jats:title>BACKGROUND:</jats:title> <jats:p>OPTIMISTmain (Main Optimal Post rtPA-IV Monitoring in Ischemic Stroke Trial) has shown that low-intensity monitoring is feasible and safe compared with standard monitoring in stable patients who receive thrombolysis treatment for acute ischemic stroke of mild-to-moderate neurological impairment. We aimed to estimate the economic benefits of low-intensity care compared with standard care.</jats:p> </jats:sec> <jats:sec> <jats:title>METHODS:</jats:title> <jats:p>A cost-minimization analysis based on OPTIMISTmain was conducted for Australia, China, Malaysia, the United Kingdom, the United States, and Vietnam. A decision tree model comprising 2 arms was developed from the trial design. State transition probabilities for each country were extracted from the trial, and cost data were sourced from the existing literature. Mean costs over the 90-day duration of follow-up were compared, and univariate and probabilistic sensitivity and scenario analyses were performed.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS:</jats:title> <jats:p>Low-intensity monitoring had the highest probability of cost saving in China (100.00%) and the United Kingdom (100.00%), followed by Australia (99.94%), the United States (95.91%), and Vietnam (86.66%), as patients in this group incurred US dollars savings of 239, 133, 647, 943, and 3 in direct costs compared with patients in the standard group, respectively. In Malaysia, however, the intervention costs slightly exceeded those for standard care (US dollars 5643 versus 5378). Countries with higher proportions of patients having intensive care unit monitoring had greater cost savings. Cost-saving thresholds of monitoring costs were 1.24, 1.30, 1.26, 1.24, 1.01, and 0.91 times the base case value in Australia, China, the United Kingdom, the United States, Vietnam, and Malaysia, respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS:</jats:title> <jats:p>The low-intensity monitoring protocol was cost saving in countries with high proportions of intensive care resources for postthrombolysis treatment monitoring, such as in the United States.</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: NCT03734640. URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.anzctr.org.au/">https://www.anzctr.org.au/</jats:ext-link> ; Unique identifier: ACTRN 12619001556134p. </jats:p> </jats:sec>
2
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Mediation Analysis to Identify Individual Component Effects of the Care Bundle to Improve Functional Outcome After ICH in the INTERACT3 Study
(Ovid Technologies (Wolters Kluwer Health), 2025-10)
Xinwen Ren
;
Qiang Li
;
Menglu Ouyang
;
Laurent Billot
;
Xiaoying Chen
1Scopus© Citations 6
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Influence of Multiple Long-Term Conditions on Outcome after Thrombolysis for Acute Ischaemic Stroke: Secondary Analysis of the ENCHANTED Trial
(S. Karger AG, 2025-08-06)
Xinwen Ren
;
Yang Zhao
;
Menglu Ouyang
;
Qiang Li
;
Chen Chen
Introduction: The influence of multiple long-term conditions on the outcomes from acute ischaemic stroke (AIS) is not well defined. This study aimed to determine the association of multiple long-term conditions in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was an international, multicentre, 2 × 2 quasi-factorial, open, randomized controlled, blinded endpoint assessed trial that assessed the effectiveness and safety of intensive blood pressure lowering and low-dose thrombolysis against standard of care in adults with AIS. Multiple long-term condition was defined as two or more coexisting chronic conditions according to medical history. The primary outcome was function recovery (distribution of scores on the modified Rankin scale) and mortality at 90 days post-randomization. Associations were estimated in multivariate logistic regression models, and an assessment of heterogeneity was undertaken in subgroups including age, sex, baseline systolic blood pressure, and clinical features. Results: In 4,566 AIS participants (mean age 66.7 years, 37.8% female), those with multiple long-term conditions were older, more often female, and had more severe neurological impairment. Multiple long-term conditions increased the odds of poor functional outcome (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI]: 1.03–1.30; p = 0.020) and mortality (aOR 1.35, 95% CI: 1.04–1.76; p = 0.024). The association between multiple long-term conditions and mortality/functional outcome was consistent across all subgroups. Conclusion: Individuals with multiple long-term conditions have higher odds of poor functional outcome and death after thrombolytic treatment for AIS.
9
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Surgical outcomes from haematoma evacuation for intracerebral haemorrhage in the INTERACT3 study
(Elsevier BV, 2025-09)
Xin Hu
;
Menglu Ouyang
;
Jianguo Xu
;
Yi Liu
;
Xi Li
1Scopus© Citations 4
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Effects of blood pressure lowering in relation to time in acute intracerebral haemorrhage: a pooled analysis of the four INTERACT trials
(Elsevier BV, 2025-07)
Xia Wang
;
Xinwen Ren
;
Qiang Li
;
Menglu Ouyang
;
Chen Chen
Scopus© Citations 1 2
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Safety and efficacy of low-intensity versus standard monitoring following intravenous thrombolytic treatment in patients with acute ischaemic stroke (OPTIMISTmain): an international, pragmatic, stepped-wedge, cluster-randomised, controlled non-inferiority trial
(Elsevier BV, 2025-05)
Craig S Anderson
;
Debbie Summers
;
Menglu Ouyang
;
Yi Sui
;
Brenda Johnson
2Scopus© Citations 15

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