强化降压对脑出血后血肿周围水肿的影响：一项系统评价和荟萃分析。
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摘要 背景：血肿周围水肿（PHE）是脑出血（ICH）所致继发性脑损伤的放射学标志。强化降压是否减轻PHE扩张仍不确定。我们进行了一项系统评价和Meta分析，以评估强化降压对自发性脑出血患者约24小时PHE扩张的影响。 方法：检索MEDLINE、Embase和Cochrane图书馆，时间从数据库建库至2026年1月。纳入研究比较了自发性脑出血患者强化降压与标准降压，并报告了PHE相关结局。使用Cochrane偏倚风险工具评估偏倚风险。使用固定效应模型的逆方差法计算合并估计值。 结果：定性综合纳入6项研究，定量Meta分析纳入4项研究，包括强化降压组1061例患者和标准血压管理组966例患者。与标准血压管理相比，强化降压与较小的约24小时PHE扩张相关（均数差，-0.50 mL；95% CI，-0.89至-0.12；p = 0.010）。未观察到统计学异质性（I2 = 0%）。 结论：强化降压与自发性脑出血患者较小的约24小时PHE扩张相关。需要进一步标准化研究来确认该效应的临床相关性。 引言 由于全球人口老龄化，卒中和脑血管疾病已成为全球第二大死亡原因以及导致永久性残疾的主要原因；然而，卒中和脑血管疾病的治疗策略仍不尽如人意（Campbell and Khatri ）。 出血性卒中 is the second most common type of stroke and occurs due to cerebral blood vessel rupture; this type of stroke accounts for approximately 20% of all strokes and is associated with disproportionately high risks of early mortality and long‐term disability (Montano et al. ). Therefore, it is necessary to develop treatments that are both practical and effective to alleviate the devastating outcomes and heavy global burden of stroke and cerebrovascular diseases (Zhang et al. ). Perihematomal edema (PHE), which can be detected in the low‐density zone surrounding hemorrhagic foci on computed tomography (CT), is regarded as a radiological marker of intracerebral hemorrhage (ICH)‐induced secondary brain injury (Greenberg et al. ). In recent years, an increasing number of studies have examined PHE as a potential therapeutic target and a surrogate measure for assessing the efficacy of emerging therapies (Wan et al. ). 高收缩压（SBP）可能促进血肿扩大，并加重脑出血（ICH）后血肿周围水肿（PHE）（Jiang et al. ），入院时血压（BP）升高与更差的神经系统预后及较高的早期和晚期死亡率相关（Green and Hemphill ）。因此，强化降压可能是急性ICH中的一种实用治疗策略。既往许多研究探讨了强化降压对PHE的影响，但结果并不一致，早期强化降压的真实效果仍不明确（Greenberg et al. ；Jiang et al. ）。为了总结现有证据并进一步探讨早期强化降压对PHE的治疗价值，我们对评估自发性ICH患者早期强化降压与PHE相关结局（尤其是约24小时PHE扩大）之间关系的研究进行了系统评价和荟萃分析。 方法 检索策略 我们在国际系统评价前瞻性注册库（PROSPERO；注册号：CRD42023405336）注册了本系统评价和Meta分析的方案。本系统评价的实施和报告遵循系统评价和Meta分析优先报告条目（PRISMA）2020声明。我们系统检索了Ovid平台的MEDLINE、Ovid平台的Embase以及Cochrane图书馆，检索时间从建库至2026年1月，以识别比较自发性脑出血（ICH）患者强化降压与标准降压并报告血肿周围水肿（PHE）相关结局的随机对照研究。检索策略结合了与ICH、血压降低、抗高血压治疗以及随机或对照试验相关的术语。各数据库的完整检索策略见补充附录。检索日期和最终分析方法根据现有证据和可提取的结局数据，在注册方案基础上进行了更新。 检索记录导入EndNote X9（Clarivate Analytics，费城，宾夕法尼亚州，美国），并移除重复记录。两位评审员独立筛选标题和摘要，随后对可能符合纳入条件的报告进行全文评估。分歧通过讨论解决，直至达成共识。研究若满足以下所有标准则被纳入：（1）入组患者年龄18岁及以上；（2）纳入自发性脑出血（ICH）患者；（3）采用随机对照试验设计，比较强化降压与标准或基于指南的血压管理；（4）报告脑水肿或血肿周围水肿（PHE）结局。研究若满足以下任一标准则被排除：（1）非人类研究；（2）不涉及自发性ICH的研究；（3）非随机研究；（4）没有随机强化降压组和标准降压组的研究；（5）未报告脑水肿或PHE结局的研究。所有符合条件的研究均纳入定性综合。仅当研究报告了PHE变化、扩大或适用时的扩大率（数据来源于基线CT和约24小时随访CT，随访时间按各原始试验方案定义），这些研究才被纳入定量荟萃分析。必须有足够的数据来提取或计算均数差及其相应方差。 两位评审员使用标准化的数据提取表独立地从符合条件的研究中提取数据。提取的数据包括作者、出版年份、试验名称、研究设计、样本量、患者特征、血压治疗目标、降压药物、影像学时间点、PHE测量方法以及水肿相关结局。对于定量荟萃分析，我们提取了PHE变化、扩张或扩张率（如适用），以及相应的样本量、均值、标准差、标准误、95%置信区间或其他计算相应方差所需的数据。 采用Cochrane偏倚风险工具（Higgins等）评估纳入的随机对照试验的偏倚风险。评估的领域包括随机序列生成、分配隐藏、参与者和人员设盲、结局评估设盲、不完整结局数据、选择性报告以及其他潜在偏倚来源。每个领域被判定为具有低、高或不清楚的偏倚风险。两位评审员独立进行评估，分歧通过讨论解决，直至达成共识。 统计分析 统计分析采用R 4.5.2版本及meta包进行。主要效应指标为强化降压组与标准降压组之间约24小时血肿周围水肿（PHE）扩大的均数差（MD）。选择MD是因为纳入研究提供了连续的水肿相关结局，可表示为PHE增长、变化或扩大的组间差异。当报告标准误或95%置信区间时，使用Cochrane手册推荐的标准公式将其转换为标准差或标准误 (Higgins et al. )。 合并估计值采用逆方差法计算，该方法根据每项研究效应估计的精确度对其赋权。采用固定效应模型作为主要模型，因为只有少数研究符合定量合并条件，导致研究间方差估计不稳定。作为敏感性分析，使用随机效应模型重新计算合并估计值，研究间方差采用限制性最大似然法估计。统计学异质性采用Cochran's Q检验和I²统计量评估 (Higgins and Thompson )。由于荟萃分析纳入的研究少于10项，未正式评估发表偏倚 (Higgins et al. )。 结果 检索结果与研究特征 数据库检索识别出 2278 条记录。去除 862 条重复记录后，1416 条记录通过标题和摘要进行筛选，其中 1341 条被排除。对 75 篇报告的全文进行了资格评估。共有 6 项研究符合资格标准，被纳入定性综合。其中，4 项研究提供了约 24‐h 血肿周围水肿（PHE）扩张的充分数据，并被纳入定量荟萃分析。未纳入定量综合的那 2 项研究报告了 PHE 相关结局，但缺乏可用于荟萃分析的方差数据。研究筛选过程如图 . 所示。 研究筛选过程流程图。 纳入的 6 项研究为随机试验或随机试验的二次分析，比较了成人自发性脑出血（ICH）患者中强化降压与标准或基于指南的血压管理。这些研究的特征，包括研究设计和血肿位置、样本量、血压目标、降压药物、用于 PHE 评估的 CT 时机、PHE 测量方法以及荟萃分析状态，总结于表 . 中。纳入定量荟萃分析的研究的人口统计学和影像学特征分别总结于表 和 中。 研究特征。 注：主要分析仅考虑 24‐h PHE 数据。当 PHE 变化或水肿增长的方差数据不可提取时，研究被排除在荟萃分析之外。 缩写：ABC/2，椭球体积估算法；ACEI，血管紧张素转换酶抑制剂；ATACH‐2，急性脑出血降压治疗2试验；BP，血压；CCBs，钙通道阻滞剂；CT，计算机断层扫描；GTN，硝酸甘油；HU，亨斯菲尔德单位；ICH ADAPT，脑出血急性期降动脉压试验；INTERACT，急性脑出血强化降压试验；IV，静脉注射；MAP，平均动脉压；NCCT，非增强计算机断层扫描；PHE，血肿周围水肿；RCT，随机对照试验；ROI，感兴趣区；SBP，收缩压。 纳入研究的人口学特征。 McCourt 2014 ICH ADAPT Yang 2015 INTERACT pooled Leasure 2019 ATACH‐2 注：数值以均值（SD）、中位数（IQR）、中位数（范围）或n（%）表示，如所示。 a通过合并各试验组特异性均值和SD值计算。 b数值显示为强化/对照组，因为总体值未直接报告。 cKoch等人报告GCS为中位数（范围），而非中位数（IQR）。Koch等人报告了入院MAP，但未报告入院SBP或DBP；未直接报告从ICH发病到CT的时间。 缩略语：ATACH-2，急性脑出血降压治疗-2；CT，计算机断层扫描；DBP，舒张压；GCS，格拉斯哥昏迷量表；ICH ADAPT，脑出血急性期降压试验；INTERACT，急性脑出血强化降压试验；IQR，四分位距；NR，未报告；SBP，收缩压；SD，标准差。 纳入研究的影像学特征。 注：数值以均值 ± 标准差、中位数（IQR）、仅中位数或校正估计值（95% CI）表示，视具体情况而定。 a 对于Yang等人的研究，血肿体积数据通过汇总原始INTERACT和INTERACT2试验报告中各治疗组的CT亚组数据计算所得；这些样本量对应于血肿影像队列（Anderson et al.；Anderson et al.）。 b 对于Yang等人的研究，PHE数据取自Yang等人2015/INTERACT的PHE汇总分析；这些样本量对应于用于PHE增长比较和定量荟萃分析的PHE分析队列。PHE分析队列与血肿影像队列不同。对于Yang等人的研究，基线PHE值报告为中位数，而PHE增长/扩张值为校正估计值，而非原始均值 ± 标准差。 缩写：ATACH-2，急性脑出血降压治疗-2；CI，置信区间；CT，计算机断层扫描；ICH ADAPT，脑出血急性期降压试验；INTERACT，急性脑出血强化降压试验；IQR，四分位数间距；NR，未报道；PHE，血肿周围水肿；SD，标准差。 质量评估。 所有 6 项纳入研究均采用随机对照设计，或是源自随机试验的二次分析。Koch 等人使用编号信封进行治疗分配，神经系统和影像学结局在治疗分配设盲的情况下进行评估（Koch 等）。ATACH‐2 试验采用基于网络的随机化；由于血压管理的性质，治疗医师未设盲，但临床结局和基于 CT 的脑出血/脑水肿（ICH/PHE）测量由设盲人员评估（Qureshi 和 Palesch）。INTERACT 和 INTERACT2 试验使用安全的基于网络的随机化系统，并采用开放标签的血压管理；然而，通过记录随机化后治疗并以标准化和设盲方式评估影像学测量和临床结局，偏倚风险得以最小化（Anderson 等；Anderson 等）。ICH ADAPT 方案规定在试验开始前使用随机数字生成器进行分配，各中心将治疗分配方案存放于按顺序拆封的密封、不透明信封中，以保证分配隐藏（Butcher 等）。Gong 等人 () 报道了强化与标准抗高血压治疗的随机分配，但分配隐藏和设盲的细节有限。Zang 等人 () 使用 SAS 生成的随机序列和密封信封，并报道了设盲结局评估。主要的潜在偏倚来源是治疗临床医师未设盲，因为血压目标干预通常为开放标签，而设盲或独立的影像学评估减少了检测偏倚。 用于 PHE 结局。使用 Cochrane 偏倚风险工具进行的偏倚风险评估的详细结果显示在图 。 质量评估。 定性综合 共有6项研究涉及血压管理和血肿周围水肿（PHE）。结果不完全一致，反映了血压目标、影像检查时机、水肿定义和分析方法的差异。Koch等人发现标准降压与强化降压之间的血肿或水肿增长无显著差异，尽管水肿估计的方向有利于强化降压（Koch等）。McCourt等人（），使用ICH ADAPT数据，通过手动感兴趣区（ROIs）和5–23亨氏单位（HU）阈值方法测量水肿，发现在最初24小时内较低与较高收缩压目标之间的绝对或相对水肿增长无显著差异；血肿周围脑血流量和收缩压降低均不能预测水肿增长。Yang等人汇总了INTERACT和INTERACT2 CT亚研究数据，报告强化降压组的校正后24‐h PHE增长小于指南组；PHE增长也与90天死亡或残疾独立相关。然而，在多变量预测模型中，随机化强化降压治疗未被保留为PHE增长的独立预测因子（Yang等）。Leasure等人（）专门评估了深部ICH中的血肿周围水肿扩张率（PHER），发现强化降压与24‐h PHER降低相关，且在基底节出血中比丘脑出血中具有更强的临床相关信号。 Gong 等 () 和 Zang 等 () 报道了支持加强的或早期强化的降压治疗的研究结果，特别是在较晚的影像学时间点，但这 2 项研究未提供可提取的 24 小时血肿周围水肿（PHE）变化或水肿增长的方差数据，并且仅保留在定性合成中。总体而言，定性证据表明，在某些特定情况下，强化降压可能减轻 PHE 扩张，尤其是在水肿以血肿周围水肿比率（PHER）评估或在较晚随访时间点评估时。不一致的研究结果可能反映了 PHE 测量方法、随访 CT 时间、血肿位置、达到的血压差异、样本量以及可提取方差数据的可用性方面的差异。 定量荟萃分析 定量荟萃分析纳入 4 项研究。与标准血压管理相比，强化降压与约 24 小时 PHE 变化或扩张更小相关（MD = −0.50 mL；95% CI，−0.89 至 −0.12；p = 0.010）。Yang 等达到了统计学显著性，而其他 3 项研究显示出支持强化降压的一致但非显著性效应。未观察到统计学异质性（χ2 = 1.00，df = 3，p = 0.802；I 2 = 0%）。使用随机效应模型的敏感性分析中，合并估计值未改变（MD = −0.50 mL；95% CI，−0.89 至 −0.12；p = 0.010）。图展示了主要的固定效应分析。 森林图。 本系统评价和荟萃分析提示，强化降压可能减轻自发性脑出血（ICH）后早期血肿周围水肿（PHE）的扩大。合并结果支持强化降压，且效应方向在定量合成的各研究中一致。这些发现支持血压控制在调节ICH后早期水肿形成中的潜在作用。PHE是ICH后继发性脑损伤的重要组成部分，可能加重占位效应、增加颅内压（ICP），并恶化神经功能预后(Marchina et al. )。早期PHE形成与血肿驱动的过程相关，包括血块回缩、凝血酶激活、炎症反应、红细胞裂解、血脑屏障（BBB）破坏以及静水压或渗透压梯度(Bautista et al. ; Chen et al. )。由于血压可能影响血肿扩大和血肿周围的静水压，因此早期降压可减轻早期PHE形成在生物学上是合理的(Chen et al. ; Minhas et al. )。本荟萃分析表明，强化降压与约24‐h时较小的PHE扩大相关。ICH后BBB破坏允许水和血浆蛋白进入血肿周围区域，且包括ICP和血压在内的静水压梯度促使后续血管源性PHE形成(Jiang et al. ; Stokum et al. )。因此，未控制的血压可能通过增加静水压而加重早期PHE形成。然而，血压降低后
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【Abstract】 BACKGROUND: Perihematomal edema (PHE) is a radiological marker of intracerebral hemorrhage (ICH)-induced secondary brain injury. Whether intensive blood pressure (BP) reduction attenuates PHE expansion remains uncertain. We conducted a systematic review and meta-analysis to assess the effect of intensive BP reduction on approximately 24-h PHE expansion in patients with spontaneous ICH. METHODS: MEDLINE, Embase, and the Cochrane Library were searched from database inception to January 2026. Eligible studies compared intensive versus standard BP reduction in patients with spontaneous ICH and reported PHE-related outcomes. Risk of bias was assessed using the Cochrane risk-of-bias tool. Pooled estimates were calculated using the inverse-variance method with a fixed-effect model. RESULTS: Six studies were included in the qualitative synthesis, and 4 studies were included in the quantitative meta-analysis, comprising 1061 patients in the intensive BP reduction group and 966 patients in the standard BP management group. Intensive BP reduction was associated with smaller approximately 24-h PHE expansion than standard BP management (mean difference, -0.50 mL; 95% CI, -0.89 to -0.12; p = 0.010). No statistical heterogeneity was observed (I2 = 0%). CONCLUSIONS: Intensive BP reduction was associated with smaller approximately 24-h PHE expansion in patients with spontaneous ICH. Further standardized studies are needed to confirm the clinical relevance of this effect. 【Introduction】 Due to the aging of the global population, stroke and cerebrovascular diseases have become the second leading cause of death worldwide and leading causes of permanent disability; however, the treatment strategies for stroke and cerebrovascular diseases remain suboptimal (Campbell and Khatri ). Hemorrhagic stroke is the second most common type of stroke and occurs due to cerebral blood vessel rupture; this type of stroke accounts for approximately 20% of all strokes and is associated with disproportionately high risks of early mortality and long‐term disability (Montano et al. ). Therefore, it is necessary to develop treatments that are both practical and effective to alleviate the devastating outcomes and heavy global burden of stroke and cerebrovascular diseases (Zhang et al. ). Perihematomal edema (PHE), which can be detected in the low‐density zone surrounding hemorrhagic foci on computed tomography (CT), is regarded as a radiological marker of intracerebral hemorrhage (ICH)‐induced secondary brain injury (Greenberg et al. ). In recent years, an increasing number of studies have examined PHE as a potential therapeutic target and a surrogate measure for assessing the efficacy of emerging therapies (Wan et al. ). High systolic blood pressure (SBP) may promote hematoma enlargement and exacerbate PHE after ICH (Jiang et al. ), and elevated blood pressure (BP) at admission is correlated with worse neurological outcomes and high rates of early and late mortality (Green and Hemphill ). Therefore, intensive BP reduction may be a practical therapeutic strategy in acute ICH. Many previous studies have explored the effect of intensive BP reduction on PHE, but the results have been inconsistent, and the true effect of early intensive BP reduction remains uncertain (Greenberg et al. ; Jiang et al. ). To summarize the existing evidence and further explore the therapeutic value of early intensive BP reduction for PHE, we conducted a systematic review and meta‐analysis of studies that assessed the association between early intensive BP reduction and PHE‐related outcomes in patients with spontaneous ICH, particularly approximately 24‐h PHE expansion. 【Methods】 【Search Strategy】 We registered the protocol for this systematic review and meta‐analysis in the International Prospective Register of Systematic Reviews (PROSPERO; registration ID: CRD42023405336). The review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement. We systematically searched MEDLINE via Ovid, Embase via Ovid, and the Cochrane Library from database inception to January 2026 to identify randomized controlled studies comparing intensive versus standard blood pressure reduction in patients with spontaneous ICH and reporting PHE‐related outcomes. The search strategy combined terms related to ICH, blood pressure lowering, antihypertensive treatment, and randomized or controlled trials. The full search strategies for each database are provided in Supplementary Appendix . The search date and final analytic approach were updated from the registered protocol according to the available evidence and extractable outcome data. 【Study Selection】 Search records were imported into EndNote X9 (Clarivate Analytics, Philadelphia, PA, USA), and duplicate records were removed. Two reviewers independently screened titles and abstracts, followed by full‐text assessment of potentially eligible reports. Discrepancies were resolved through discussion until consensus was reached. Studies were included if they met all of the following criteria: (1) enrolled patients aged 18 years or older; (2) included patients with spontaneous ICH; (3) used a randomized controlled trial design comparing intensive blood pressure reduction with standard or guideline‐based blood pressure management; and (4) reported brain edema or PHE outcomes. Studies were excluded if they met any of the following criteria: (1) non‐human studies; (2) studies not involving spontaneous ICH; (3) non‐randomized studies; (4) studies without randomized intensive and standard blood pressure reduction groups; or (5) studies without brain edema or PHE outcomes. All eligible studies were included in the qualitative synthesis. Studies were included in the quantitative meta‐analysis only if they reported PHE change, expansion, or expansion rate where applicable, derived from baseline CT and an approximately 24‐h follow‐up CT, with follow‐up timing defined according to each original trial protocol. Sufficient data had to be available to extract or calculate the mean difference and its corresponding variance. 【Data Extraction and Quality Assessment】 Two reviewers independently extracted data from eligible studies using a standardized data extraction form. Extracted data included author, publication year, trial name, study design, sample size, patient characteristics, blood pressure treatment targets, antihypertensive agents, imaging time points, PHE measurement methods, and edema‐related outcomes. For the quantitative meta‐analysis, we extracted PHE change, expansion, or expansion rate where applicable, together with the corresponding sample size, mean, standard deviation, standard error, 95% confidence interval, or other data required to calculate the corresponding variance. The risk of bias of included randomized controlled trials was assessed using the Cochrane risk‐of‐bias tool (Higgins et al. ). The assessed domains included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other potential sources of bias. Each domain was judged as having low, high, or unclear risk of bias. Two reviewers performed the assessment independently, and disagreements were resolved through discussion until consensus was reached. 【Statistical Analysis】 Statistical analyses were performed using R version 4.5.2 with the meta package. The primary effect measure was the mean difference (MD) in approximately 24‐h PHE expansion between the intensive and standard blood pressure reduction groups. The MD was selected because the included studies provided continuous edema‐related outcomes that could be expressed as between‐group differences in PHE growth, change, or expansion. When standard errors or 95% confidence intervals were reported, they were converted to standard deviations or standard errors using standard formulae recommended in the Cochrane Handbook (Higgins et al. ). Pooled estimates were calculated using the inverse‐variance method, which weights each study according to the precision of its effect estimate. A fixed‐effect model was used as the primary model because only a small number of studies were eligible for quantitative synthesis, making between‐study variance estimation unstable. As a sensitivity analysis, the pooled estimate was recalculated using a random‐effects model, with between‐study variance estimated using the restricted maximum‐likelihood method. Statistical heterogeneity was assessed using Cochran's Q test and the I 2 statistic (Higgins and Thompson ). Publication bias was not formally assessed because fewer than 10 studies were included in the meta‐analysis (Higgins et al. ). 【Results】 【Search Results and Study Characteristics】 Database searches identified 2278 records. After removal of 862 duplicates, 1416 records were screened by title and abstract, of which 1341 were excluded. The full texts of 75 reports were assessed for eligibility. A total of 6 studies met the eligibility criteria and were included in the qualitative synthesis. Among these, 4 studies provided sufficient data on approximately 24‐h PHE expansion and were included in the quantitative meta‐analysis. The 2 studies not included in the quantitative synthesis reported PHE‐related outcomes but lacked extractable variance data for the meta‐analysis. The study selection process is shown in Figure . Flowchart of the study selection process. The 6 included studies were randomized trials or secondary analyses of randomized trials comparing intensive blood pressure reduction with standard or guideline‐based blood pressure management in adults with spontaneous ICH. The characteristics of these studies, including study design and hematoma location, sample size, blood pressure targets, antihypertensive agents, CT timing for PHE assessment, PHE measurement methods, and meta‐analysis status, are summarized in Table . The demographic and imaging characteristics of the studies included in the quantitative meta‐analysis are summarized in Tables and , respectively. Study characteristics. Note: Only 24‐h PHE data were considered for the primary analysis. Studies were excluded from the meta‐analysis when variance data for change in PHE or edema growth were not extractable. Abbreviations: ABC/2, ellipsoid volume estimation method; ACEI, angiotensin‐converting enzyme inhibitor; ATACH‐2, Antihypertensive Treatment of Acute Cerebral Hemorrhage‐2; BP, blood pressure; CCBs, calcium channel blockers; CT, computed tomography; GTN, glyceryl trinitrate; HU, Hounsfield units; ICH ADAPT, Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial; INTERACT, Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial; IV, intravenous; MAP, mean arterial pressure; NCCT, noncontrast computed tomography; PHE, perihematomal edema; RCT, randomized controlled trial; ROI, region of interest; SBP, systolic blood pressure. Demographics of included studies. McCourt 2014 ICH ADAPT Yang 2015 INTERACT pooled Leasure 2019 ATACH‐2 Note: Values are presented as mean (SD), median (IQR), median (range), or n (%), as indicated. aCalculated by pooling arm‐specific mean and SD values. bValues are shown as intensive/control because the overall value was not directly reported. cKoch et al. reported GCS as median (range), not median (IQR). Koch et al. reported admission MAP, but not admission SBP or DBP; time from ICH onset to CT was not directly reported. Abbreviations: ATACH‐2, Antihypertensive Treatment of Acute Cerebral Hemorrhage‐2; CT, computed tomography; DBP, diastolic blood pressure; GCS, Glasgow Coma Scale; ICH ADAPT, Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial; INTERACT, Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial; IQR, interquartile range; NR, not reported; SBP, systolic blood pressure; SD, standard deviation. Imaging characteristics of included studies. Note: Values are presented as mean ± SD, median (IQR), median only, or adjusted estimate (95% CI), as indicated. a For Yang et al., hematoma volume data were calculated by pooling arm‐specific CT subgroup data from the original INTERACT and INTERACT2 trial reports; these sample sizes correspond to the hematoma imaging cohort (Anderson et al. ; Anderson et al. ). b For Yang et al., PHE data were extracted from the Yang et al. 2015/INTERACT pooled PHE analysis; these sample sizes correspond to the PHE analysis cohort used for the PHE growth comparison and quantitative meta‐analysis. The PHE analysis cohort differed from the hematoma imaging cohort. For Yang et al., baseline PHE values are reported medians, whereas PHE growth/expansion values are adjusted estimates, not raw mean ± SD. Abbreviations: ATACH‐2, Antihypertensive Treatment of Acute Cerebral Hemorrhage‐2; CI, confidence interval; CT, computed tomography; ICH ADAPT, Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial; INTERACT, Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial; IQR, interquartile range; NR, not reported; PHE, perihematomal edema; SD, standard deviation. 【Quality Assessment】 All 6 included studies employed randomized controlled designs or were secondary analyses derived from randomized trials. Koch et al. used numbered envelopes for treatment allocation, and neurological and radiological outcomes were assessed blinded to treatment allocation (Koch et al. ). The ATACH‐2 trial used web‐based randomization; treating physicians were not blinded because of the nature of BP management, but clinical outcomes and CT‐based ICH/PHE measurements were assessed by blinded personnel (Qureshi and Palesch ). The INTERACT and INTERACT2 trials used secure web‐based randomization systems with open‐label BP management; however, the risk of bias was minimized by documenting post‐randomization treatments and by assessing imaging measurements and clinical outcomes in a standardized and blinded manner (Anderson et al. ; Anderson et al. ). The ICH ADAPT protocol specified allocation using a random number generator before trial commencement, with treatment assignments stored in sequentially opened sealed, opaque envelopes at each site to assure allocation concealment (Butcher et al. ). Gong et al. () reported random allocation to strengthened versus standard antihypertensive treatment, but details of allocation concealment and blinding were limited. Zang et al. () used SAS‐generated random sequences and sealed envelopes, and reported blinded outcome assessment. The main potential source of bias was the lack of blinding of treating clinicians because BP‐target interventions were generally open‐label, whereas blinded or independent imaging assessment reduced detection bias for PHE outcomes. The detailed results of the risk‐of‐bias assessment using the Cochrane risk‐of‐bias tool are shown in Figure . Quality assessment. 【Qualitative Synthesis】 There were 6 studies involving BP management and PHE. The findings were not fully consistent, reflecting differences in BP targets, imaging timing, edema definitions, and analytic approaches. Koch et al. found no significant difference in hematoma or edema growth between standard and aggressive BP reduction, although the direction of the edema estimate favored aggressive BP lowering (Koch et al. ). McCourt et al. (), using ICH ADAPT data, measured edema with manual regions of interest (ROIs) and a 5–23 Hounsfield unit (HU) threshold method and found no significant difference in absolute or relative edema growth between lower and higher SBP targets during the first 24 h; neither perihematoma cerebral blood flow nor SBP reduction predicted edema growth. Yang et al. analyzed pooled INTERACT and INTERACT2 CT substudy data and reported smaller adjusted 24‐h PHE growth in the intensive BP reduction group than in the guideline group; PHE growth was also independently associated with 90‐day death or dependency. However, randomized intensive BP treatment was not retained as an independent predictor of PHE growth in the multivariable predictor model (Yang et al. ). Leasure et al. () specifically evaluated perihematomal edema expansion rate (PHER) in deep ICH and found that intensive BP reduction was associated with decreased 24‐h PHER, with a stronger clinically relevant signal in basal ganglia hemorrhage than in thalamic hemorrhage. Gong et al. () and Zang et al. () reported findings favoring strengthened or early intensive antihypertensive treatment, particularly at later imaging time points, but these 2 studies did not provide extractable variance data for 24‐h PHE change or edema growth and were retained in the qualitative synthesis only. Taken together, the qualitative evidence suggests that intensive BP reduction may attenuate PHE expansion in selected settings, especially when edema is assessed as PHER or at later follow‐up time points. The inconsistent findings likely reflect differences in PHE measurement methods, follow‐up CT timing, hematoma location, achieved BP separation, sample size, and availability of extractable variance data. 【Quantitative Meta‐Analysis】 The quantitative meta‐analysis included 4 studies. Intensive BP reduction was associated with smaller approximately 24‐h PHE change or expansion than standard BP management (MD = −0.50 mL; 95% CI, −0.89 to −0.12; p = 0.010). Yang et al. reached statistical significance, while the other 3 studies showed consistent but nonsignificant effects favoring intensive BP reduction. No statistical heterogeneity was observed (χ2 = 1.00, df = 3, p = 0.802; I 2 = 0%). The pooled estimate was unchanged in a sensitivity analysis using a random‐effects model (MD = −0.50 mL; 95% CI, −0.89 to −0.12; p = 0.010). Figure presents the primary fixed‐effect analysis. Forest plot. 【Discussion】 This systematic review and meta‐analysis suggests that intensive BP reduction may attenuate early PHE expansion after spontaneous ICH. The pooled result favored intensive BP reduction, and the direction of effect was consistent across the quantitatively synthesized studies. These findings support a potential role of BP control in modulating early edema formation after ICH. PHE is an important component of secondary brain injury after ICH and may aggravate mass effect, increase intracranial pressure (ICP), and worsen neurological outcomes (Marchina et al. ). Early PHE formation is related to hematoma‐driven processes, including clot retraction, thrombin activation, inflammatory responses, erythrocyte lysis, blood–brain barrier disruption, and hydrostatic or osmotic pressure gradients (Bautista et al. ; Chen et al. ). Because BP may influence hematoma expansion and hydrostatic pressure around the hematoma, it is biologically plausible that early BP reduction could attenuate early PHE formation (Chen et al. ; Minhas et al. ). This meta‐analysis indicated that intensive BP reduction was associated with smaller approximately 24‐h PHE expansion. BBB disruption after ICH permits the movement of water and plasma proteins into the perihematomal region, and the hydrostatic pressure gradient, which includes ICP and BP, contributes to subsequent vasogenic PHE formation (Jiang et al. ; Stokum et al. ). Therefore, uncontrolled BP may exacerbate early PHE formation by increasing hydrostatic pressure. However, BP reduction afte