OPTIMAL-BP
Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke
Year of Publication: 2023
Authors: Hyo Suk Nam, Young Dae Kim, JoonNyung Heo, ..., for the OPTIMAL-BP Trial Investigators
Journal: JAMA
Citation: JAMA. 2023;330(9):832-842.
Link: https://jamanetwork.com/journals/jama/fullarticle/2808869
PDF: Clinical Question
Does intensive blood pressure management (SBP <140 mmHg) during the first 24 hours after successful EVT lead to better functional outcomes than conventional BP management (SBP 140-180 mmHg) in acute ischemic stroke from large vessel occlusion?
Bottom Line
Intensive BP lowering (SBP <140 mmHg) after successful EVT was harmful: functional independence at 3 months was significantly lower (39.4% vs 54.4%; adjusted OR 0.56; 95% CI 0.33-0.96; P=0.03). Malignant cerebral edema was significantly more frequent (7.7% vs 1.3%; adjusted OR 7.88; P=0.01). sICH rates were similar (9.0% vs 8.1%). Trial terminated early for safety/futility (conditional power 1.22%).
Major Points
- Intensive BP lowering was harmful: SBP <140 mmHg for 24h after EVT reduced functional independence from 54.4% to 39.4% (adjusted OR 0.56; 95% CI 0.33-0.96; P=0.03).
- Malignant cerebral edema significantly increased: 7.7% intensive vs 1.3% conventional (adjusted OR 7.88; 95% CI 1.57-39.39; P=0.01).
- No benefit for sICH: 9.0% intensive vs 8.1% conventional (P=0.82).
- Death within 3 months: 7.7% vs 5.4% (P=0.31), not significant but numerically higher with intensive management.
- Trial stopped early: DSMB recommended termination for futility (conditional power 1.22%) and safety concerns from concurrent ENCHANTED2/MT results.
- BP separation achieved: 24h mean SBP 129.2 vs 138.0 mmHg (difference -9.6 mmHg; P<0.001).
- mRS shift analysis also favored conventional: adjusted OR 0.65 (95% CI 0.43-0.97; P=0.04).
- Reverse J-shaped curve: post hoc analysis showed very low SBP in intensive group associated with worst outcomes.
- All subgroup analyses favored conventional management β no significant interactions.
- Consistent with ENCHANTED2/MT: both trials showed intensive BP lowering after EVT worsens outcomes. SBP 140-180 mmHg appears adequate.
Design
Study Type: Multicenter, randomized, open-label, blinded endpoint (PROBE) clinical trial
Randomization: 1
Blinding: Open-label; blinded endpoint evaluation (PROBE). mRS by certified staff blinded to allocation. Neuroimaging adjudicated centrally by blinded reviewers. Permuted block (size 4), stratified by hospital and NIHSS (<15 vs β₯15).
Enrollment Period: June 18, 2020 to November 29, 2022
Follow-up Duration: 3 months
Centers: 19
Countries: South Korea
Sample Size: 302
Analysis: Intention-to-treat (primary); per-protocol (sensitivity). Binary logistic regression for primary outcome. Planned sample 668; stopped early at 306.
Inclusion Criteria
- Adults aged β₯20 years.
- Underwent EVT for acute ischemic stroke due to large vessel occlusion.
- Successful reperfusion (mTICI β₯2b).
- Elevated SBP β₯140 mmHg on β₯2 measurements within 2-minute interval.
- Measurements taken within 2 hours of successful reperfusion.
Exclusion Criteria
- SBP <140 mmHg after successful reperfusion (n=705 excluded).
- Contraindication to antihypertensive medications.
- sICH evident during or immediately after EVT.
- Serious medical or surgical illness.
- Prestroke disability (mRS 3-5).
- Reperfusion failure (mTICI β€2a).
- Participation in a study not allowing dual enrollment.
- Age <20 years.
Baseline Characteristics
| Characteristic | Intensive (N=155) | Conventional (N=147) |
|---|---|---|
| Age (meanΒ±SD) | 73.2Β±12.1 | 72.9Β±10.8 |
| Female sex | 63 (40.6%) | 59 (40.1%) |
| Hypertension | 121 (78.1%) | 110 (74.8%) |
| Atrial fibrillation | 77 (49.7%) | 69 (46.9%) |
| Diabetes | 65 (41.9%) | 62 (42.2%) |
| Hyperlipidemia | 61 (39.4%) | 54 (36.7%) |
| Smoking | 39 (25.2%) | 29 (19.7%) |
| Previous stroke | 36 (23.2%) | 30 (20.4%) |
| NIHSS median (IQR) | 13 (6) | 12 (7) |
| IV tPA use | 44 (28.4%) | 54 (36.7%) |
| TOAST Cardioembolic | 76 (49.0%) | 76 (51.7%) |
| TOAST Large artery | 41 (26.5%) | 43 (29.3%) |
| Onset to puncture median (IQR) | 388 (223.5-692.5) min | 357 (209-725) min |
| Puncture to reperfusion median (IQR) | 30 (22-47) min | 31 (20-48) min |
| Mean SBP at enrollment (Β±SD) | 155.2Β±13.4 mmHg | 154.8Β±14.4 mmHg |
| Intracranial stent/angioplasty | 25.2% | 21.1% |
Arms
| Field | Intensive BP Management | Control |
|---|---|---|
| Intervention | SBP target <140 mmHg for 24 hours after enrollment. Goal to reach target within 1 hour. Continuous noninvasive BP monitoring. IV BP-lowering drugs (nicardipine preferred) used in 74.2%. Time in target: 83.0%. 24h mean SBP achieved: 129.2Β±7.7 mmHg. | SBP target 140-180 mmHg for 24 hours after enrollment. Vasopressors NOT used if SBP dropped below 140. IV BP-lowering drugs used in 18.7%. Time in target: 42.1% (SBP often spontaneously <140). 24h mean SBP: 138.0Β±13.6 mmHg. |
| Duration | 24 hours post-enrollment | 24 hours post-enrollment |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Functional independence at 3 months (mRS 0-2) | Primary | 80/147 (54.4%) | 61/155 (39.4%) | 0.03 | |
| mRS shift analysis (ordinal) | Secondary | β | β | Adjusted OR 0.65 | 0.04 |
| Excellent recovery at 24h (NIHSS 0-1 or β₯8pt improvement) | Secondary | 37/148 (25.0%) | 25/153 (16.3%) | Adjusted OR 0.62 | 0.11 |
| Successful reperfusion at 24h | Secondary | 132/141 (93.6%) | 132/146 (90.4%) | OR 0.64 | 0.37 |
| Functional independence at 1 month (mRS 0-2) | Secondary | 72/144 (50.0%) | 56/150 (37.3%) | Adjusted OR 0.65 | 0.12 |
| EQ-5D-3L at 3 months (meanΒ±SD) | Secondary | 0.61Β±0.40 | 0.50Β±0.43 | Adjusted Ξ² -0.08 | 0.05 |
| sICH within 36h | Adverse | 12/149 (8.1%) | 14/155 (9.0%) | Adjusted OR 1.10 | 0.82 |
| Death within 3 months | Adverse | 8/147 (5.4%) | 12/155 (7.7%) | Adjusted OR 1.73 | 0.31 |
| Malignant cerebral edema within 36h | Adverse | 2/149 (1.3%) | 12/155 (7.7%) | Adjusted OR 7.88 | 0.01 |
| SBP drop <100 mmHg | Adverse | 17.3% | 29.7% |
Subgroup Analysis
No significant interactions across prespecified subgroups (age, sex, time from onset, NIHSS). All point estimates favored conventional management.
Criticisms
- Early termination: 306 vs planned 668 patients β reduced power and risk of overestimated treatment effects.
- Only 19.1% of screened patients enrolled; ~half excluded because SBP <140 β selection bias.
- Conventional group spent only 42.1% in target range (SBP often spontaneously <140) β may have underpowered the comparison.
- Wide CI for malignant edema (OR 7.88, CI 1.57-39.39) β small events, model instability.
- South Korean population only β may not generalize to other ethnicities.
- Open-label intervention (though blinded endpoint).
- Cannot determine optimal drug class β nicardipine most common but not mandated.
Funding
Patient-Centered Clinical Research Coordinating Center (PACEN), Ministry of Health and Welfare, Republic of Korea (Grant HC19C0028).
Based on: OPTIMAL-BP (JAMA, 2023)
Authors: Hyo Suk Nam, Young Dae Kim, JoonNyung Heo, ..., for the OPTIMAL-BP Trial Investigators
Citation: JAMA. 2023;330(9):832-842.
Content summarized and formatted by NeuroTrials.ai.