Pooled Analysis From the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies

Acute spontaneous intracerebral hemorrhage (ICH) affects several million people worldwide each year, resulting in a heavy burden of premature death and disability. The cerebral injury from ICH involves several overlapping mechanisms beginning with physical disruption and mass effect from the hematoma and associated cerebral edema and later from the consequences of the toxic effects of hemoglobin breakdown products, free radicals, and inflammation. Initial volume and subsequent growth of the hematoma are pivotal to determining outcome in ICH, but perihematomal edema (PHE) also contributes to the risk of death and disability from raised intracranial pressure or hydrocephalus. Several potential time-dependent mechanisms underlie the formation of PHE: an early phase (the first hours) of hydrostatic pressure and clot retraction from serum moving out of the hematoma and into surrounding cerebral tissue; and a later phase that Background and Purpose—Controversy exists over the prognostic significance of perihematomal edema (PHE) in intracerebral hemorrhage. We aimed to determine the association of early PHE and clinical outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies. Methods—Pooled analyses of computed tomographic substudies in the pilot phase (INTERACT1) and main phase (INTERACT2), both international, prospective, open, blinded end point, randomized controlled trials, of patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure, randomly assigned to intensive (target systolic blood pressure, <140 mm Hg) or guideline-based (systolic blood pressure, <180 mm Hg) blood-pressure management. Substudy participants (n=1310; 346 INTERACT1, 964 INTERACT2) had blinded central analyses of digital images from standardized baseline and 24-hour computed tomography. Predictors of death or dependency (modified Rankin scale scores, ≥3) at 90 days were assessed in logistic regression models and reported with odds ratios and 95% confidence intervals. INTERACT studies are registered at ClinicalTrials.gov (NCT00226096 and NCT00716079). Results—Of 1138 (87%) patients with 2 CTs available for edema analysis and outcome information, time from intracerebral hemorrhage onset to baseline computed tomography, baseline hematoma volume, 24-hour hematoma growth, and intraventricular extension were independent predictors of 24-hour PHE growth. Absolute growth in PHE volume was significantly associated with death or dependency (adjusted odds ratio, 1.17; 95% confidence interval, 1.02–1.33 per 5 mL increase from baseline; P=0.025) at 90 days after adjustment for demographic, clinical, and hematoma parameter prognostic factors. Associations were consistent across various sensitivity analyses. Conclusion—PHE growth is an independent prognostic factor in intracerebral hemorrhage. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079. (Stroke. 2015;46:1009-1013. DOI: 10.1161/STROKEAHA.114.007154.)