Early blood pressure lowering and cerebral oedema in thrombolysis-treated stroke: secondary analysis of the ENCHANTED trial

BACKGROUND AND PURPOSE: Controversy persists over the balance of benefits and harms of early intensive blood pressure (BP) lowering in thrombolysis-treated acute ischaemic stroke (AIS) patients. The BP-control arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) (n=2196) showed that compared with guideline-recommended management (systolic BP (SBP)<180 mm Hg), intensive BP lowering did not improve functional outcome despite reducing intracranial haemorrhage. We aimed to evaluate the relationship between the BP parameters and cerebral oedema in ENCHANTED BP-control arm participants. METHODS: ENCHANTED was an international, multicentre, open-label, blinded outcome assessed, randomised controlled trial in thrombolysed AIS patients. All baseline and follow-up brain images were centrally analysed using standardised techniques and planimetric software by expert readers blind to clinical details. The severity of cerebral oedema was measured on a 7-point scale that ranged from 0 (no oedema) to 6 (most severe oedema); the primary outcome of 'severe cerebral oedema' defined by scores 4-6. RESULTS: 1477 (67.3%) participants (mean age 67.7 years, 39.6% female) with available cerebral oedema data were included. Patients with a larger magnitude of SBP reduction in 1 hour had a lower odds of severe cerebral oedema (adjusted OR 0.72 per 10 mm Hg, 95% CI 0.53 to 0.98; p=0.04), whereas those with greater SBP variability between 1 hour and 24 hours had a shift towards worse cerebral oedema (adjusted OR 1.27 per 10 mm Hg, 95% CI 1.01 to 1.60; p=0.04). CONCLUSION: Although the effect size is modest, achieving rapid lowering of SBP within 1 hour and then maintaining stable SBP over 24 hours appears to be associated with less cerebral oedema in thrombolysis-treated AIS patients. CLINICAL TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT01422616).