PDF: OPTIMAL-BP
(2023)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
• 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 ≥140 mm Hg were randomized to either intensive BP target (<140 mm Hg) or conventional target (140–180 mm Hg) for 24 hours. BP was managed using IV antihypertensives, primarily nicardipine.
Study Design
Arms: Intensive BP Management vs Conventional BP Management
Outcome
• Symptomatic ICH: 9.0% (intensive) vs. 8.1% (conventional), p=0.82
• Death within 3 months: 7.7% (intensive) vs. 5.4% (conventional), p=0.31
• Malignant cerebral edema: 7.7% (intensive) vs. 1.3% (conventional), adjusted OR 7.88 (95% CI 1.57–39.39), p=0.01
• Shift analysis: worse mRS in intensive group, adjusted OR 0.65 (95% CI 0.43–0.97), p=0.04
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 — no significant interactions.
- Consistent with ENCHANTED2/MT: both trials showed intensive BP lowering after EVT worsens outcomes. SBP 140-180 mmHg appears adequate.
Study Design
- Study Type
- Multicenter, randomized, open-label, blinded endpoint (PROBE) clinical trial
- Randomization
- Yes
- 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 ≥15).
- Sample Size
- 302
- Follow-up
- 3 months
- Centers
- 19
- Countries
- South Korea
Primary Outcome
Definition: Functional independence at 3 months (mRS 0-2)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 80/147 (54.4%) | 61/155 (39.4%) | - (0.33-0.96) | 0.03 |
Limitations & Criticisms
- Early termination: 306 vs planned 668 patients — reduced power and risk of overestimated treatment effects.
- Only 19.1% of screened patients enrolled; ~half excluded because SBP <140 — selection bias.
- Conventional group spent only 42.1% in target range (SBP often spontaneously <140) — may have underpowered the comparison.
- Wide CI for malignant edema (OR 7.88, CI 1.57-39.39) — small events, model instability.
- South Korean population only — may not generalize to other ethnicities.
- Open-label intervention (though blinded endpoint).
- Cannot determine optimal drug class — nicardipine most common but not mandated.
Citation
JAMA. 2023;330(9):832-842.