Abstract Background and aims The treatment effect of intensive blood pressure (BP) lowering on functional outcomes across hematoma locations remains unclear in acute intracerebral hemorrhage (ICH). We aimed to examine whether ICH location modifies this treatment effect. Methods We conducted an individual patient data meta-analysis of five international randomized controlled trials (INTERACT1-4 and ATACH-2) investigating intensive BP-lowering. ICH location was classified as lobar, deep, or infratentorial. Functional outcome was death or major disability (mRS 3-6 at 90 days). Treatment effects in each ICH-location subgroup were examined using generalized linear mixed models with a logit link, including trial as a random effect, relevant clinical variables as fixed effects, and a treatment-by-location interaction term to assess effect modification by ICH location. Results Of 11,288 patients (mean age 63 years; 36% female), 1,141 (10.1%), 9,202 (81.5%), and 945 (8.4%) cases presented with lobar, deep, and infratentorial ICH, respectively. Compared with ICHs located at deep or infratentorial, those at lobar were older, less likely to have intraventricular hemorrhage, presented with larger hematoma volumes (all P 0.001). There was heterogeneity across ICH-location subgroups regarding the treatment effect of intensive BP-lowering to improve functional outcomes (p for interaction = 0.033), with a significant benefit evident only in deep ICH (odds ratio OR 0.81, 95%CI 0.74-0.89, P 0.001). Conclusions ICH location modifies the treatment effect of intensive BP-lowering on improving functional outcomes, with the benefit observed only in deep ICH. These findings highlight the potential for a targeted therapeutic strategy and inform the design of future trials focusing on patients most likely to benefit. Conflict of interest Xinwen Ren: nothing to disclose.
Ren et al. (2026) studied this question.