Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies

Stroke. 2015 Apr;46(4):1009-13. doi: 10.1161/STROKEAHA.114.007154. Epub 2015 Feb 24.


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 (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: Unique identifier: NCT00226096 and NCT00716079.

Keywords: cerebral hemorrhage; clinical trial; hypertension.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects
  • Brain Edema / diagnostic imaging*
  • Brain Edema / mortality
  • Cerebral Hemorrhage / diagnostic imaging*
  • Cerebral Hemorrhage / mortality
  • Disease Progression*
  • Female
  • Hematoma, Subdural, Intracranial / diagnostic imaging
  • Hematoma, Subdural, Intracranial / mortality
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Radiography
  • Severity of Illness Index
  • Single-Blind Method
  • Time Factors


  • Antihypertensive Agents

Associated data