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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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Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke
(Ovid Technologies (Wolters Kluwer Health), 2024-12-10)
Yanan Wang
;
Toshiki Maeda
;
Shoujiang You
;
Chen Chen
;
Leibo Liu
2
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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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Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage
(2013)
Craig S. Anderson
;
Emma Heeley
;
Yining Huang
;
Jiguang Wang
;
Christian Stapf
Scopus© Citations 1333 1
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Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial
(2014)
Lisa Manning
;
Yoichiro Hirakawa
;
Hisatomi Arima
;
Xia Wang
;
John Chalmers
2Scopus© Citations 261
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Clinical Prediction Algorithm (BRAIN) to Determine Risk of Hematoma Growth in Acute Intracerebral Hemorrhage
(2015)
Xia Wang
;
Hisatomi Arima
;
Rustam Al-Shahi Salman
;
Mark Woodward
;
Emma Heeley
<jats:sec> <jats:title>Background and Purpose—</jats:title> <jats:p>We developed and validated a simple algorithm to predict the risk of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) to better inform clinicians and researchers in their efforts to improve outcomes for patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods—</jats:title> <jats:p>We analyzed data from the computed tomography substudies of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and 2, respectively). The study group was divided into a derivation cohort (INTERACT2, n=964) and a validation cohort (INTERACT1, n=346). Multivariable logistic regression was used to identify factors associated with clinically significant (≥6 mL) increase in hematoma volume at 24 hours after symptom onset. A parsimonious risk score was developed on the basis of regression coefficients derived from the logistic model.</jats:p> </jats:sec> <jats:sec> <jats:title>Results—</jats:title> <jats:p> A 24-point BRAIN score was derived from INTERACT2 (C-statistic, 0.73) based on baseline ICH volume (mL per score, ≤10=0, 10–20=5, >20=7), recurrent ICH (yes=4), anticoagulation with warfarin at symptom onset (yes=6), intraventricular extension (yes=2), and number of hours to baseline computed tomography from symptom onset (≤1=5, 1–2=4, 2–3=3, 3–4=2, 4–5=1, >5=0) predicted the probability of ICH growth (ranging from 3.4% for 0 point to 85.8% for 24 points) with good discrimination (C-statistic, 0.73) and calibration (Hosmer–Lemeshow <jats:italic>P</jats:italic> =0.82) in INTERACT1. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>The simple BRAIN score predicts the probability of hematoma growth in ICH. This could be used to improve risk stratification for research and clinical practice.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration—</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifier: NCT00226096 and NCT00716079. </jats:p> </jats:sec>
3Scopus© Citations 117
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Low Ambient Temperature and Intracerebral Hemorrhage: The INTERACT2 Study
(2016)
Danni Zheng
;
Hisatomi Arima
;
Shoichiro Sato
;
Antonio Gasparrini
;
Emma Heeley
1 1Scopus© Citations 24
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Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke
(2016)
Craig S. Anderson
;
Thompson Robinson
;
Richard I. Lindley
;
Hisatomi Arima
;
LAVADOS GERMAIN, PABLO MANUEL
Scopus© Citations 381 3
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Poor utility of grading scales in acute intracerebral hemorrhage: results from the INTERACT2 trial
(2015)
Emma Heeley
;
Craig S. Anderson
;
Mark Woodward
;
Hisatomi Arima
;
Thompson Robinson
<jats:sec><jats:title>Background</jats:title><jats:p> Several simple clinical grading scores have been developed for intracerebral hemorrhage, primarily to predict 30-day mortality. </jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p> We aimed to determine the accuracy of three popular scores (original intracerebral hemorrhage, modified intracerebral hemorrhage, and intracerebral hemorrhage grading scale) on 30-day mortality and 90-day death or major disability, and whether the magnitude of benefit varies according to prognosis graded by the three predictive scores. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Data from the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial which included 2839 intracerebral hemorrhage patients (<6 hours) and elevated systolic blood pressure (150–220 mmHg), randomized to intensive (target systolic blood pressure <140 mmHg) or guideline-based (<180 mmHg) blood pressure management. Discrimination of scales for predicting death and poor outcome (modified Rankin scale 3–6) was evaluated in area under receiver operator characteristic curves. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Among 2556 (90%) participants with available data, the modified intracerebral hemorrhage had the highest discrimination (receiver operator characteristic 0·75) for 90-day poor outcome compared with the original intracerebral hemorrhage (receiver operator characteristic 0·68) and intracerebral hemorrhage grading scale (receiver operator characteristic 0·69). All scores had good positive predictive value (approximately 80–90%) for poor outcome but poor sensitivity and positive predictive value for death. The scores do not clearly discriminate a patient group most likely to benefit from blood pressure lowering. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> Intracerebral hemorrhage prognostic scores are not useful in defining patients at high probability of early death, but they are reliable for predicting poor outcome, defined by death or major disability. Potential benefits of early intensive blood pressure lowering are broadly applicable across grades of severity defined by such scores. </jats:p></jats:sec>
7Scopus© Citations 23

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