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

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.