Optimal Magnitude of Blood Pressure Reduction and Hematoma Growth and Functional Outcomes in Intracerebral Hemorrhage

Early intensive systolic blood pressure (SBP) reduction is a promising strategy for intracerebral hemorrhage (ICH), but the optimal magnitude of reduction in the first 2 hours remains uncertain. This study aimed to determine the optimal SBP reduction magnitude to maximize benefit in patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial. We performed a post hoc analysis of the ATACH-2 trial. Participants with baseline SBP ≥180 mm Hg were randomized within 4.5 hours from onset and assigned to the intensive or standard group. The magnitude of SBP reduction was calculated as admission SBP minus minimum SBP at 2 hours. Eligible participants were divided into 5 groups by 15 mm Hg stratum: <40, 40-55, 55-70, 70-85, and ≥85 mm Hg. Poor functional outcome was defined as the modified Rankin Scale score at 3-6 and hematoma expansion (HE) as a relative increase of >33% from baseline to 24 hours. Multivariable logistic regression assessed associations between SBP reduction and outcomes. Our study included 925 patients, of whom 360 (38.9%) were female. The median age was 62 years (IQR: 53-71). The median hematoma volume was 10.2 mL (IQR: 5.1-18.4), and the median magnitude of SBP reduction was 68 mm Hg (IQR: 48-88). Of those, 209 (22.6%) experienced HE, 122 (13.2%) experienced acute kidney injury (AKI), and 516 (55.8%) had poor outcome. Hematoma expansion decreased linearly as the magnitude of blood pressure reduction increased in 5 SBP reduction groups (p < 0.001). After multivariable adjustment, patients with a greater degree of SBP reduction (≥70 mm Hg) were less likely to experience HE and a SBP reduction ≥55 mm Hg was associated with a lower risk of poor outcomes (odds ratio [OR] 0.49, 95% CI 0.28-0.85). However, a SBP reduction ≥85 mm Hg increased AKI risk compared with <40 mm Hg (OR, 2.00; 95% CI 1.01-3.94). Targeting a SBP reduction within the range of 55-85 mm Hg during the first 2 hours seems to be associated with optimal outcomes in patients with mild-to-moderate ICH, balancing the need to limit hematoma growth while avoiding adverse effect. Further study focusing on severe ICH is warranted. Clinical trial registration number: NCT01176565. This post hoc analysis of the ATACH-2 trial provides Class III evidence that SBP reduction of 55-85 mm Hg during the initial 2 hours is associated with lower frequency of HE and better functional outcomes in patients with acute cerebral hemorrhage.