Functional Outcomes After Intensive Blood Pressure Reduction in Deep and Lobar Intracerebral Hemorrhage

Intensive blood pressure (BP) reduction may reduce the risk of poor functional outcomes in patients with acute intracerebral hemorrhage (ICH). Whether these potential benefits apply similarly to lobar and deep ICH, 2 biologically and clinically distinct subtypes, remains uncertain. We tested the hypothesis that intensive BP reduction has differential effects on functional outcomes based on ICH location.

We performed a stepwise meta-analysis, stratified by ICH location, of 3 landmark randomized clinical trials of intensive BP reduction: Acute Cerebral Hemorrhage (ATACH-2), Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), and INTERACT3. Step 1 pooled ATACH-2 and INTERACT2 (3-month outcomes; intensive BP lowering only). Step 2 added INTERACT3 (6-month outcomes; care bundle protocol with intensive BP lowering plus glucose management, antipyresis, and anticoagulant reversal). For ATACH-2, we used pooled results from individual patient data (adjusted for age, Glasgow Coma Scale score, and presence of intraventricular hemorrhage), whereas for INTERACT2 and INTERACT3, we used their pooled, publicly available results. Our exposure of interest contrasted intensive systolic BP targets <140 mm Hg vs standard care 140-180 mm Hg. Our outcome of interest was poor functional outcome, defined as a modified Rankin Scale score of 4-6 in ATACH-2 and INTERACT3 and of 3-6 in INTERACT2.

Step 1 included a total of 2,983 patients with deep and 537 patients with lobar ICH (mean age 63 y/o, 37% female). Intensive BP reduction was not associated with a significant difference in poor functional outcome for either deep (odds ratio [OR] 0.89; 95% CI 0.40-1.98; I² = 0%) or lobar (OR 0.92; 95% CI 0.73-1.17; I² = 0%) ICH. Step 2 included a total of 7,917 patients with deep and 1,105 patients with lobar ICH (mean age 63 y/o, 37% female). Similarly, intensive BP reduction was not associated with a significant difference in poor outcome in both deep (OR 0.82; 95% CI 0.57-1.18; I² = 60%) and lobar (OR 0.97; 95% CI 0.76-1.24; I² = 0%) ICH.

In this stepwise meta-analysis of 3 landmark ICH trials, intensive BP reduction did not demonstrate a significant benefit in either deep or lobar ICH. Although our estimates did not reach statistical significance, the direction of effect in deep ICH and the substantial heterogeneity across trials, particularly with the inclusion of INTERACT3, limit firm conclusions. Given these uncertainties and the biological distinctions between deep and lobar ICH, future well-powered studies specifically designed to test whether intensive BP reduction has differential effects by hematoma location are warranted.