ENCHANTED (BP after IVT)
Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial
Year of Publication: 2023
Authors: Chen Chen, Menglu Ouyang, Sheila Ong, ..., Craig S. Anderson
Journal: eClinicalMedicine
Citation: eClinicalMedicine 2023;57: 101849
Link: https://doi.org/10.1016/j.eclinm.2023.101849
PDF: https://www.ahajournals.org/doi/epub/10....EAHA.116.015594
PDF: Clinical Question
Does intensive blood pressure lowering alter the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke?
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
Design
Study Type: Prespecified secondary analysis of randomized controlled trial
Randomization: 1
Blinding: Expert readers blinded to treatment assignment
Enrollment Period: March 3, 2012 to April 30, 2018
Follow-up Duration: Brain imaging at median 26.7 hours from symptom onset
Centers: 110
Countries: Multiple international sites (15 countries)
Sample Size: 1477
Analysis: Log-linear regression models with adjustment for potential confounders. Intention-to-treat approach for patients with available brain imaging
Inclusion Criteria
- Participants from ENCHANTED trial
- Acute ischemic stroke patients eligible for thrombolysis
- Elevated systolic blood pressure >150 mmHg
- Available follow-up brain imaging
Exclusion Criteria
- Patients without available follow-up brain imaging
- Poor quality brain imaging
- Missing or uncertain timing of scans
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| Mean age | 69.0 (11.5) years | 68.7 (12.3) years |
| Female | 137/335 (41%) | 125/300 (42%) |
| Asian ethnicity | 176/335 (53%) | 165/300 (55%) |
| Median NIHSS score | 7 (4-12) | 7 (4-12) |
| Systolic BP | 166.4 (9.0) mmHg | 165.7 (9.3) mmHg |
| Hypertension | 245/335 (73%) | 213/299 (71%) |
| Mean systolic BP over 1-24h | 149 (12.7) mmHg | 141 (10.6) mmHg |
| Time from onset to randomization | 3.3 (2.6-4.0) hours | 3.3 (2.5-4.0) hours |
Arms
| Field | Intensive Blood Pressure Group | Control |
|---|---|---|
| Intervention | Systolic target 130-140 mmHg within 1 hour, maintained for 72 hours | Guideline-recommended systolic target <180 mmHg |
| Duration | 72 hours of intensive management | Standard care blood pressure management |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Size of cerebral infarction on CT scans at 24-36 hours post-randomization | Primary | 0.9 ml (IQR 0.0-12.5) | 0.3 ml (IQR 0.0-16.6) | 0.58 | |
| Infarct size on MRI at 24-36h | Secondary | 2.9 ml (0.6-17.3) | 2.3 ml (0.6-25.7) | 0.36 | |
| Infarct size on CT/MRI combined at 24-36h | Secondary | 1.3 ml (0.0-12.8) | 0.7 ml (0.0-17.5) | 0.56 | |
| Infarct size on any follow-up scan | Secondary | 1.8 ml (0.0-16.1) | 1.0 ml (0.0-18.2) | 0.36 | |
| Intracranial hemorrhage | Secondary | 16% | 13% | 0.74 | 0.21 |
| No significant safety differences | Adverse | Similar rates between groups | No increased harm from intensive BP lowering |
Subgroup Analysis
Consistent results across 10 prespecified subgroups including age, sex, ethnicity, stroke severity, and timing. Significant positive association between attained systolic BP and infarct size (log mean difference 0.20 per 10 mmHg increase, 95% CI 0.03-0.38, p=0.02).
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
Funding
National Health and Medical Research Council of Australia; UK Stroke Association; UK Dementia Research Institute; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda
Based on: ENCHANTED (BP after IVT) (eClinicalMedicine, 2023)
Authors: Chen Chen, Menglu Ouyang, Sheila Ong, ..., Craig S. Anderson
Citation: eClinicalMedicine 2023;57: 101849
Content summarized and formatted by NeuroTrials.ai.