ENCHANTED (Swelling Analysis)
Effects of Intensive Blood Pressure Lowering on Brain Swelling in Thrombolyzed Acute Ischemic Stroke: The ENCHANTED Results
Clinical Question
Does early intensive blood pressure lowering reduce cerebral swelling in patients with acute ischemic stroke treated with thrombolysis?
Bottom Line
Early intensive BP lowering to 130–140 mm Hg did not significantly reduce cerebral swelling compared to guideline-recommended BP control (<180 mm Hg) in thrombolyzed patients with AIS.
Major Points
- Secondary analysis of the ENCHANTED trial focused on cerebral swelling after IV alteplase in AIS.
- 1477/2196 patients had analyzable brain imaging; randomized to intensive (n=719) vs. guideline (n=746) BP control.
- No significant difference in cerebral swelling: 22.12% vs 22.39% (aOR 1.05, 95% CI 0.81–1.36; p=0.71).
- Ordinal shift in swelling scores and midline shift measurements showed no significant differences.
- BP difference between groups was modest (mean Δ 6.6 mm Hg).
- Reassuring safety data support intensive BP lowering in thrombolyzed AIS but no benefit on brain swelling.
Design
Study Type: Randomized, open-label, blinded endpoint (PROBE) trial
Randomization: 1
Blinding: Blinded imaging endpoint assessment
Enrollment Period: March 2012 – April 2018
Follow-up Duration: Imaging at 24–96 hours (median 27.4h)
Centers: 110
Countries: Australia, China, Korea, Brazil, Chile, UK
Sample Size: 2196
Analysis: Logistic and ordinal regression, intention-to-treat, adjusted for clinical covariates
Inclusion Criteria
- Acute ischemic stroke eligible for IV thrombolysis
- Systolic BP ≥150 mm Hg at baseline
- Treatment within 6 hours of symptom onset
Exclusion Criteria
- Contraindication to thrombolysis
- Severe comorbid illness or anticipated poor prognosis
- Unavailable follow-up brain imaging
Arms
| Field | Intensive BP lowering | Control |
|---|---|---|
| Intervention | IV BP-lowering agents to target systolic 130–140 mm Hg within 1 hour, maintained for 72h | Standard BP management to systolic <180 mm Hg |
| Duration | 72 hours | 72 hours |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Any brain swelling (score 1–6) on follow-up imaging | Primary | 22.12% | 22.39% | 0.71 | |
| Swelling score 2–6 | Secondary | 10.46% | 10.01% | 1.00 | |
| Change in swelling score (worsened) | Secondary | 28.61% | 27.98% | 0.55 | |
| Midline shift (mm) | Secondary | 8.85 mm | 6.47 mm | 0.17 | |
| Parenchymal hemorrhage (PH1/2) | Adverse | 8% | 6% | 0.12 |
Subgroup Analysis
No heterogeneity across prespecified subgroups (age, sex, SBP, time to randomization, scan type, infarct size, alteplase dose, premorbid status, etc.)
Criticisms
- Modest BP difference between groups (6.6 mm Hg) may have limited detectable effect
- Swelling scale may not capture true edema volume
- Only 67% of trial population included due to imaging availability
- Follow-up imaging often closer to 24h than 72h—may miss peak swelling
- Secondary analysis not powered for edema outcome
Funding
National Health and Medical Research Council of Australia, Stroke Association (UK), CNPq (Brazil), Ministry of Health (Korea)
Based on: ENCHANTED (Swelling Analysis) (Stroke, 2025)
Authors: Guobin Zhang, Chen Chen, Xinwen Ren, ..., for the ENCHANTED Investigators
Citation: Stroke. 2025;56:1388–1395. DOI: 10.1161/STROKEAHA.124.049938
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