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ENCHANTED (Swelling Analysis)

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

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Year of Publication: 2025

Authors: Guobin Zhang, Chen Chen, Xinwen Ren, ..., for the ENCHANTED Investigators

Journal: Stroke

Citation: Stroke. 2025;56:1388–1395. DOI: 10.1161/STROKEAHA.124.049938

Link: https://www.ahajournals.org/doi/10.1161/STROKEAHA.124.049938

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	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

Content summarized and formatted by NeuroTrials.ai.

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

• Intensive BP lowering did not significantly reduce cerebral swelling compared to guideline BP management.
• 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 sites 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

• Any brain swelling (score 1–6): 22.1% (intensive) vs. 22.4% (guideline); adjusted OR 1.05 (95% CI 0.81–1.36), P=0.71
• Moderate-to-severe swelling (score 3–6): 3.26% vs. 2.55%; adjusted OR 1.62 (95% CI 0.85–3.08), P=0.15
• Worsening swelling: 28.0% vs. 28.6%; adjusted OR 1.12 (95% CI 0.78–1.59), P=0.55
• Midline shift (mm): 6.47 (guideline) vs. 8.85 (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 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.

Study Design

Study Type: Randomized, open-label, blinded endpoint (PROBE) trial
Randomization: Yes
Blinding: Blinded imaging endpoint assessment
Sample Size: 2196
Follow-up: Imaging at 24–96 hours (median 27.4h)
Centers: 110
Countries: Australia, China, Korea, Brazil, Chile, UK

Primary Outcome

Definition: Any brain swelling (score 1–6) on follow-up imaging

Control	Intervention	HR/OR	P-value
22.12%	22.39%	- (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

View Original Publication →

ENCHANTED (Swelling Analysis)

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

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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