Association of Intensive Blood Pressure Reduction with Risk of Hematoma Expansion in Patients with Deep Intracerebral Hemorrhage

Importance: Hypertension is the strongest risk factor for spontaneous intracerebral hemorrhage (ICH) involving deep brain regions, but it appears to be unknown if intensive blood pressure reduction in the acute care setting decreases hematoma expansion or improves outcomes in patients with deep ICH. Objective: To determine whether intensive blood pressure reduction is associated with decreased risk of hematoma expansion and changes in 90-day modified Rankin Scale scores and if these associations are modified by the specific deep-brain nuclei involved. Design, Setting, and Participants: This study is an exploratory analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 international, multicenter randomized clinical trial, which was conducted from May 2011 to September 2015, enrolled eligible patients with primary ICH, and followed up with them for 90 days. Patients who had ICH and complete neuroimaging data were included in the analysis. Data analysis was completed from July 2018 to December 2018. Exposures: Participants were randomized to either intensive treatment (with a systolic blood pressure target of 110-139 mm Hg) or standard treatment (with a systolic blood pressure target of 140-179 mm Hg). Main Outcomes and Measures: The main outcome was hematoma expansion, defined as an increase greater than 33% in hematoma volume between baseline and 24 hours. Functional outcome was evaluated 90 days after the ICH via the modified Rankin Scale. Results: Of 1000 trial participants, 870 (87.0%) had deep ICH, of whom 780 (89.7%) had complete neuroimaging data (of 336 thalamic and 444 basal ganglia hemorrhages). The baseline characteristics of the intensive and standard treatment groups remained balanced in this subgroup of the original study. Intensive treatment was associated with a decreased risk of hematoma expansion in univariable analysis (odds ratio [OR], 0.62 [95% CI, 0.43-0.87]; P =.006) and multivariable analysis (OR, 0.61 [95% CI, 0.42-0.88]; P =.009). This association was modified by the specific deep location of the ICH (OR, 0.44 [95% CI, 0.22-0.96]; interaction P =.02), with stratified analyses showing a reduction in risk of hematoma expansion with intensive vs standard treatment among basal ganglia ICH (OR, 0.44 [95% CI, 0.27-0.72]; P =.001) but not thalamic ICH (OR, 0.91 [95% CI, 0.51-0.64]; P =.76). Intensive treatment was not associated with an improvement in the modified Rankin Scale score distribution. Conclusions and Relevance: Compared with standard treatment, intensive blood pressure treatment was associated with reduced hematoma expansion in deep ICH, specifically among basal ganglia hemorrhages.