BP-TARGET
Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial
Clinical Question
Does intensive systolic blood pressure lowering (100-129 mm Hg) after successful endovascular therapy for acute ischaemic stroke reduce intraparenchymal haemorrhage rates compared with a standard target (130-185 mm Hg)?
Study Overview
Objective
To assess whether an intensive systolic blood pressure target (100-129 mm Hg) reduces intraparenchymal haemorrhage rates compared with a standard target (130-185 mm Hg) after successful endovascular therapy for acute ischaemic stroke.
Study Summary
- Intensive SBP lowering (100-129 mm Hg) did NOT reduce radiographic intraparenchymal haemorrhage vs standard care (130-185 mm Hg)
- Primary outcome occurred in 42% (65/154) intensive vs 43% (68/157) standard (adjusted OR 0.96, 95% CI 0.60-1.51; p=0.84)
- Mean SBP achieved: 128 mm Hg (SD 11) intensive vs 138 mm Hg (SD 17) standard
- Hypotensive events numerically higher with intensive: 8% (12/158) vs 3% (5/160)
- 1-week mortality: 7% (11/158) intensive vs 4% (7/160) standard
Intervention
Intravenous antihypertensive treatment (first-line nicardipine infusion) to achieve target SBP within 1 hour of randomisation and maintained for 24 hours after successful endovascular therapy.
Patients per Arm
162 per arm (324 total randomised)
Bottom Line
An intensive systolic BP target of 100-129 mm Hg after successful endovascular thrombectomy did NOT reduce radiographic intraparenchymal haemorrhage rates at 24-36 h compared with a standard target of 130-185 mm Hg. Routine intensive BP lowering after successful reperfusion is not supported by this trial.
Major Points
- First RCT to test intensive BP lowering after successful endovascular thrombectomy
- Neutral primary outcome: no reduction in radiographic intraparenchymal haemorrhage (42% vs 43%; adjusted OR 0.96, 95% CI 0.60-1.51; p=0.84)
- Achieved a meaningful ~10 mm Hg separation in mean SBP (128 vs 138 mm Hg over 24 h)
- Numerically higher hypotensive events (8% vs 3%) and 1-week mortality (7% vs 4%) with intensive lowering
- Challenges the assumed causal link between post-reperfusion BP and haemorrhage
- Results applicable to patients with SBP >130 mm Hg at end of successful EVT procedure
Design
Study Type: Multicentre, open-label, randomised controlled trial
Randomization: 1
Blinding: Open-label (participants and treating physicians unmasked); outcome assessments done by qualified investigators not involved in randomisation or treatment
Allocation: 1:1 via central web-based procedure, block size of 4, stratified by centre and IV alteplase use before EVT
Enrollment Period: June 21, 2017 to September 27, 2019
Follow-up Duration: 3 months (mRS and serious adverse events)
Centers: 4
Countries: France
Sample Size: 324
Analyzed: 318
Analysis: Intention-to-treat
Power Calculation: Planned to randomly assign 320 individuals (160 per group) to have 80% power at 0.05 significance (two-sided Z-test with pooled variance) to detect an absolute 15% decrease in intraparenchymal haemorrhage rate with intensive SBP lowering (from an assumed 40% rate in the standard group to an expected 25% rate in the intensive group), accounting for an anticipated 5% rate of missing follow-up CT scans.
Registration: ClinicalTrials.gov NCT03160677
Inclusion Criteria
- Age ≥18 years
- Acute ischaemic stroke due to large-vessel occlusion of the anterior circulation (intracranial ICA or proximal M1 MCA, or both)
- Successful reperfusion by endovascular therapy (mTICI 2b or 3)
Exclusion Criteria
- Haemorrhagic complications during endovascular therapy
- Spontaneous SBP decrease to <130 mm Hg after reperfusion
- Severe or fatal comorbidities making the procedure unlikely to benefit the patient (e.g., malignant cancer with reduced life expectancy)
- Pre-existing stroke disability with mRS >2
- Known pregnancy
- Absence of written consent from patient or family
- Absence of social insurance scheme
Arms
| Field | Intensive SBP Target | Control |
|---|---|---|
| N | 162 | 162 |
| Intervention | Target SBP 100-129 mm Hg achieved within 1 h of randomisation and maintained for 24 h; IV antihypertensives (first-line nicardipine infusion) | Target SBP 130-185 mm Hg maintained within 1 h and for 24 h after randomisation; spontaneous drops <130 mm Hg accepted (no vasopressors) |
| Duration | 24 hours | 24 hours |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Rate of radiographic intraparenchymal haemorrhage on brain CT | Primary | 68/157 (43%) | 65/154 (42%) | 0.96 | 0.84 |
| Favourable functional outcome (mRS 0-2) at 3 months | Secondary | Adjusted OR 0.93 (95% CI 0.58-1.48) | |||
| Excellent functional outcome (mRS 0-1) at 3 months | Secondary | Adjusted OR 1.20 (95% CI 0.72-1.97) | |||
| mRS shift analysis at 3 months (scores 5 and 6 combined) | Secondary | Adjusted OR 0.86 (95% CI 0.57-1.28) per 1-point improvement | |||
| Change in NIHSS score from admission to 24 h | Secondary | Mean difference 0.3 (95% CI -1.7 to 2.3) | |||
| Hypotensive events (primary safety outcome; SBP <80 mm Hg within 24 h) | Safety | Adjusted OR 2.53 (95% CI 0.86-7.41) | |||
| Symptomatic intraparenchymal haemorrhage at 24-36 h | Safety | Adjusted OR 1.68 (95% CI 0.75-3.77) | |||
| Parenchymal haematoma type 2 at 24-36 h | Safety | Adjusted OR 1.30 (95% CI 0.58-2.89) | |||
| All-cause mortality at 3-month follow-up (secondary safety) | Safety | Adjusted OR 1.46 (95% CI 0.80-2.63) | |||
| Adverse | Event: Recurrent ischaemic stroke (within 1 week) · Intensive: 0 · Standard: 1/160 (<1%) | ||||
| Adverse | Event: Stroke worsening (NIHSS increase >4 without parenchymal haemorrhage, within 1 week) · Intensive: 1/158 (<1%) · Standard: 0 | ||||
| Adverse | Event: Hemicraniectomy · Intensive: 1/158 (<1%) · Standard: 0 | ||||
| Adverse | Event: Hypotensive events requiring intervention (fluids or vasopressors) · Intensive: 0 · Standard: 0 | ||||
| Adverse | Event: Neurological-related mortality within first week · Intensive: 8/158 (5%) · Standard: 7/160 (4%) | ||||
| Adverse | Event: Non-neurological-related mortality within first week · Intensive: 3/158 (2%) · Standard: 0 | ||||
| Adverse | Event: Mortality within 3 months · Intensive: 29/152 (19%) · Standard: 21/153 (14%) | ||||
Subgroup Analysis
Prespecified subgroup analyses (adjusted OR for primary outcome, intensive vs standard) were consistent with the neutral overall result: age ≤80 years aOR 0.73 (95% CI 0.41-1.29) vs >80 years aOR 1.53 (0.71-3.26); isolated MCA occlusion aOR 1.03 (0.60-1.74) vs tandem MCA/ICA aOR 0.87 (0.35-2.15); no prior IV alteplase aOR 0.88 (0.45-1.71) vs alteplase aOR 1.03 (0.55-1.91). An unplanned centre-level analysis showed heterogeneity, driven by a lower-than-expected primary outcome rate in the standard group at the two smaller centres (centre 3 aOR 3.75, 95% CI 0.87-16.10).
Criticisms
- Open-label design (though outcome assessors were independent)
- Radiographic (not clinical/symptomatic) intraparenchymal haemorrhage as primary endpoint — clinical significance of asymptomatic haemorrhage debated
- Only patients with SBP >130 mm Hg at end of EVT procedure were effectively studied (those spontaneously <130 mm Hg were excluded)
- Restricted to anterior circulation large-vessel occlusion
- Conducted in France only — generalisability to other healthcare systems uncertain
- 3-month functional outcomes (mRS) not reported as primary endpoint
- Numerical excess of hypotension and early mortality with intensive lowering warrants caution
Funding
French Health Ministry
Based on: BP-TARGET (Lancet Neurology, 2021)
Authors: Mazighi M, Richard S, Lapergue B, ..., Piotin M; BP-TARGET investigators
Citation: Lancet Neurol 2021; 20: 265-74
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