PDF: ENCHANTED (BP after IVT)
(2023)Objective
To determine whether intensive blood pressure lowering altered the size of cerebral infarction in thrombolysed patients with acute ischemic stroke
Study Summary
• Primary analysis on CT at 24-36h showed no difference in median infarct size (0.3 vs 0.9 ml, p=0.58)
• Results were consistent across sensitivity analyses and subgroups
Intervention
Intensive blood pressure lowering (systolic target 130-140 mmHg within 1h, maintained 72h) vs guideline-recommended management (systolic target <180 mmHg)
Inclusion Criteria
Patients from ENCHANTED trial with hypertension (systolic BP >150 mmHg) after thrombolysis treatment for acute ischemic stroke, with available follow-up brain imaging
Study Design
Arms: Intensive group (n=300) vs Guideline group (n=335) for primary CT analysis
Patients per Arm: 1477 total patients with follow-up imaging; 635 with CT at 24-36h (300 intensive, 335 guideline)
Outcome
• Consistent results across MRI and combined imaging analyses
• Positive association found between attained systolic BP and infarct size
Bottom Line
Intensive blood pressure lowering to a systolic target <140 mmHg within several hours after stroke onset may not increase the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke of mild to moderate neurological severity.
Major Points
- This was a prespecified secondary analysis of the ENCHANTED trial brain imaging data
- 1477 patients (67.3%) had available follow-up brain imaging for analysis, including 635 patients with CT at 24-36 hours
- Mean achieved systolic blood pressures over 1-24 hours were 141 mmHg (intensive) vs 149 mmHg (guideline)
- No significant effect of intensive BP lowering on median infarct size on CT at 24-36h (0.3 vs 0.9 ml, log Δmean -0.17, 95% CI -0.78 to 0.43, p=0.58)
- Results were consistent across sensitivity analyses with MRI and combined imaging approaches
- Significant positive association found between attained systolic BP and infarct size (22% increase per 10 mmHg increase)
- J-shaped association with smallest infarcts at systolic BP 110-120 mmHg
Study Design
- Study Type
- Prespecified secondary analysis of randomized controlled trial
- Randomization
- Yes
- Blinding
- Expert readers blinded to treatment assignment
- Sample Size
- 1477
- Follow-up
- Brain imaging at median 26.7 hours from symptom onset
- Centers
- 110
- Countries
- Multiple international sites (15 countries)
Primary Outcome
Definition: Size of cerebral infarction on CT scans at 24-36 hours post-randomization
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 0.9 ml (IQR 0.0-12.5) | 0.3 ml (IQR 0.0-16.6) | - (-0.78 to 0.43) | 0.58 |
Limitations & Criticisms
- Selection bias due to incomplete brain imaging collection (only 67.3% of trial participants)
- Most patients had mild to moderate neurological impairment with correspondingly low infarct volumes
- Brain imaging conducted according to routine local practice rather than standardized protocol
- Modest difference in achieved systolic BP between groups may limit power to detect differences
- Challenging assessment primarily on CT images rather than more sensitive MRI
- Missing brain imaging data in 719 patients, mainly due to investigators failing to upload images
Citation
eClinicalMedicine 2023;57: 101849