Effects of Blood Pressure Lowering by Hematoma Location in Acute Intracerebral Hemorrhage.

Abstract

Background and objectives: Early intensive blood pressure (BP) lowering is now recognized as an effective approach to improve outcome after acute intracerebral hemorrhage (ICH). However, whether the effect varies by hematoma location is uncertain. We aimed to determine the heterogeneity of the treatment effect of intensive BP lowering on functional outcome by hematoma location.

Methods: We conducted a pooled analysis of individual patient-level data (IPD) from all 4 Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT) and the second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trial, which were international, randomized, open, blinded end point assessed, controlled trials that investigated the effectiveness of early intensive BP control in acute ICH. ICH location was classified as lobar or deep hemisphere or infratentorial. The primary outcome was death or disability (modified Rankin Scale scores 3-6) at 90 days or 6 months (for INTERACT3). The heterogeneity of the treatment effect of intensive BP lowering on the primary outcome by ICH location was estimated using generalized linear mixed models with trial as a random effect and adjustment for prespecified clinical covariates and an interaction term of "treatment-by-location."

Results: Among 11,288 patients (mean age 62.5 years [SD 12.7]; 4,056 [35.9%] women), 1,141 (10.1%) had lobar ICH, 9,202 (81.5%) had deep ICH and 945 (8.4%) had infratentorial ICH. Compared with deep or infratentorial ICH, lobar ICH occurred in older patients, was less often associated with intraventricular hemorrhage, and had larger hematoma volumes (all p < 0.001). The effect of intensive BP lowering on the primary outcome of death or disability differed by ICH location (p for interaction = 0.033). A clear benefit was only seen in deep ICH (adjusted odds ratio 0.81, 95% CI 0.74-0.89; p < 0.001).

Discussion: Hematoma location modifies the treatment effect of intensive BP lowering on functional outcome after ICH, with the benefit observed only in deep ICH.

Trial registration information: These trials are registered at ClinicalTrials.gov (INTERACT1 NCT00226096; INTERACT2 NCT00716079; INTERACT3 NCT03209258; INTERACT4 NCT03790800; and ATACH-II NCT01176565).