OPTIMAL-BP
Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial
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?
Study Overview
Objective
To determine whether intensive blood pressure (BP) lowering during the first 24 hours after successful reperfusion improves functional outcomes in patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke.
Study Summary
- Intensive systolic BP control (<140 mm Hg) after EVT resulted in worse 3-month functional outcomes compared to conventional BP targets (140β180 mm Hg).
- The trial was terminated early due to safety concerns and low conditional power.
- No significant difference in symptomatic ICH or mortality between groups.
- Malignant cerebral edema was significantly more frequent in the intensive BP group.
Intervention
Patients with successful EVT and SBP β₯140 mm Hg were randomized to either intensive BP target (<140 mm Hg) or conventional target (140β180 mm Hg) for 24 hours. BP was managed using IV antihypertensives, primarily nicardipine.
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; 95% CI 1.57-39.39; 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 related to the index stroke 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: 306
Analysis: 306 randomized; primary analysis was modified ITT β all randomized participants who provided consent, excluding withdrawal of consent prior to BP control, non-receipt of allocated treatment, and loss to follow-up before 3 months (n=302 analyzed: 155 intensive, 147 conventional). Full ITT is reported in the supplement (eTable 2). Per-protocol sensitivity analysis included 288 patients. Binary logistic regression for primary outcome, adjusted for age, sex, onset-to-randomization time, and NIHSS immediately before EVT. 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.
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 |
| NIHSS score at 24 h (meanΒ±SD) | Secondary | 9.59 (7.45) | 11.56 (7.48) | Adjusted difference 1.05 | 0.10 |
| Excellent recovery at 24h (NIHSS 0-1 or improvement of >8 points) | 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%) | Unadjusted OR 0.64; Adjusted OR 0.66 | 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 related to the index stroke 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% | 0.02 |
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.
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