Effects of Intensive Blood Pressure Lowering on Brain Swelling in Thrombolyzed Acute Ischemic Stroke: The ENCHANTED Results

Abstract

Background: Cerebral swelling in relation to cytotoxic edema is a predictor of poor outcome in acute ischemic stroke (AIS) and elevated blood pressure (BP) promotes its development. Whether intensive BP-lowering treatment reduces cerebral swelling is uncertain. We aimed to determine whether intensive BP lowering reduces the severity of cerebral swelling after thrombolysis for AIS.

Methods: A secondary analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial factorial, international, multicenter, open-label, blinded end point, randomized controlled trial of alteplase dose and levels of BP control in thrombolyzed patients with AIS. Participants were randomly assigned to intensive (systolic target 130-140 mm Hg within 1 hour; maintained for 72 hours) or guideline-recommended (systolic target <180 mm Hg) BP management. Available serial brain images (baseline and follow-up, computed tomography, or magnetic resonance imaging) were centrally analyzed with standardized techniques (Apollo MIStar software) by expert readers blind to clinical details to rate swelling severity (from 0 no to 6 most severe swelling [midline shift and effacement of basal cisterns]) and other abnormalities. Primary outcome was any cerebral swelling (score, 1-6) in logistic regression models.

Results: Of 1477/2196 (67.3%) patients (mean age, 67.7 years; female, 39.6%) with sequential scans, the between-group mean systolic BP difference was 6.6 mm Hg over 24 hours. No significant difference was found in the treatment effect on any cerebral swelling between intensive and guideline-recommended BP management (22.12% versus 22.39%, adjusted odds ratio, 1.05 [95% CI, 0.81-1.36]; P=0.71). Results were consistent across different groups of swelling severity (swelling score 2-6, 3-6, and 4-6; and ordinal shift on swelling score).

Conclusions: Modest early intensive BP lowering does not seem to alter cerebral swelling in thrombolyzed patients with AIS. Further research is needed to quantify brain edema to allow a better understanding of the complex relations of BP and outcomes from AIS.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616.

Keywords: blood pressure; brain edema; clinical trial; ischemic stroke; thrombolytic therapy.