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
Journal
Annals of Neurology
ISSN
0364-5134
Date Issued
2026-04-01
Author(s)
Xinwen Ren
Qiang Li
Menglu Ouyang
Xiaoying Chen
Chen Chen
Candice Delcourt
Jiguang Wang
Thompson Robinson
Hisatomi Arima
Lu Ma
Chao You
Gang Li
Jie Yang
Yapeng Lin
Leibo Liu
Sheila Martins
Octavio Marques Pontes‐Neto
Adnan I. Qureshi
Xin Hu
Lili Song
Craig S. Anderson
Xia Wang
Type
journal-article
Abstract
<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>
<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>