ENCHANTED (Swelling Analysis)
(2025)Objective
To determine whether intensive early blood pressure lowering (<140) reduces the severity of cerebral swelling in patients with acute ischemic stroke (AIS) treated with thrombolysis.
Study Summary
• No difference in midline shift, worsening edema, or swelling severity scores.
• Supports safety of early intensive BP control in thrombolyzed AIS.
Intervention
Secondary analysis of the ENCHANTED trial (randomized, open-label, blinded-endpoint, partial factorial design) comparing intensive BP lowering (SBP target 130–140 mmHg within 1 hour, maintained 72h) vs. guideline BP control (SBP <180 mmHg) in 2196 AIS patients treated with IV alteplase. Brain swelling assessed on follow-up CT/MRI scans using standardized 7-point scoring.
Inclusion Criteria
AIS patients eligible for thrombolysis, enrolled across 110 hospitals in 15 countries. Final analysis included 1477 patients with available serial imaging (mean age: 67.7; NIHSS median: 8).
Study Design
Arms: Intensive BP Control vs. Guideline BP Control
Patients per Arm: Intensive: 725; Guideline: 752
Outcome
• Moderate-to-severe swelling (score 3–6): 3.26% (intensive) vs. 2.55% (guideline); adjusted OR 1.62 (95% CI 0.85–3.08), P=0.15
• Worsening swelling: 27.98% (intensive) vs. 28.61% (guideline); adjusted OR 1.12 (95% CI 0.78–1.59), P=0.55
• Midline shift (mm): 8.85 (guideline) vs. 6.47 (intensive); adjusted difference -1.78 mm (95% CI -5.73 to 2.17), P=0.17
• No significant subgroup interactions (age, sex, NIHSS, time to randomization, infarct size, etc.)
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 any follow-up brain imaging (intensive n=725, guideline n=752); swelling score was assessed in 1465 (intensive n=719, guideline n=746).
- No significant difference in cerebral swelling: 22.12% (guideline) vs 22.39% (intensive) (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.
Study Design
- Study Type
- Randomized, open-label, blinded endpoint (PROBE) trial
- Randomization
- Yes
- Blinding
- Blinded imaging endpoint assessment
- Sample Size
- 2196
- Follow-up
- Primary follow-up imaging within 24 hours post-randomization; sensitivity analysis restricted to scans at 24–96 hours; median time from symptom onset to selected follow-up imaging 27.4h (IQR 24.6–31.9)
- Centers
- 110
Primary Outcome
Definition: Any brain swelling (score 1–6) on follow-up imaging
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 22.12% | 22.39% | 1.05 (adjusted) (0.81–1.36) | 0.71 |
Limitations & 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
Citation
Stroke. 2025;56:1388–1395. DOI: 10.1161/STROKEAHA.124.049938