PDF: BEST-II
(2023)Objective
To evaluate whether lower systolic blood pressure (SBP) targets (<140 or <160 mmHg) after successful endovascular therapy improve outcomes compared to standard guideline target (≤180 mmHg).
Study Summary
• No significant functional or imaging benefit with lower BP targets.
• Findings suggest low probability of benefit with intensive BP lowering after EVT.
Intervention
Phase 2, randomized, open-label, blinded-endpoint, futility-design trial across 3 U.S. stroke centers. Patients with acute ischemic stroke and successful EVT were randomized within 60 minutes of recanalization to one of three SBP targets (<140, <160, or ≤180 mmHg), maintained for 24 hours primarily using IV nicardipine.
Inclusion Criteria
Adults (≥18 years) with anterior circulation LVO ischemic stroke who underwent successful EVT (mTICI ≥2b). Excluded if severe cardiac dysfunction or enrolled in other trials.
Study Design
Arms: SBP <140 mmHg vs. SBP <160 mmHg vs. SBP ≤180 mmHg
Patients per Arm: <140: 40; <160: 40; ≤180: 40
Outcome
• Mean utility-weighted mRS: 0.51 (<140), 0.47 (<160), 0.58 (≤180)
• Adjusted slope of infarct volume: -0.29 mL/mmHg SBP decrease (95% CI -0.81 to ∞; futility p=0.99)
• Adjusted slope of utility-weighted mRS: -0.0019 per mmHg SBP decrease (95% CI -∞ to 0.0017; futility p=0.93)
• Symptomatic ICH: 5% (<140), 3% (<160), 5% (≤180)
• In-hospital mortality: 7.5% (<140), 15% (<160), 7.5% (≤180)
• Trial did not meet futility criteria but showed low predicted probability of benefit for lower SBP targets.
Bottom Line
Lower SBP targets after EVT did not meet prespecified futility criteria, but suggested low probability of benefit: the slope of utility-weighted mRS per mmHg decrease was -0.0019 (futility P=0.93). Functional outcomes numerically favored the ≤180 mmHg group (mean utility-weighted mRS 0.58 vs 0.51 [<140] vs 0.47 [<160]). Predicted probability of success for a future superiority trial was only 25% for <140 mmHg and 14% for <160 mmHg at maximum sample size of 1,500.
Major Points
- Futility result (functional outcome): slope of utility-weighted mRS per mmHg decrease was -0.0019 (95% CI -∞ to 0.0017; futility P=0.93).
- Futility result (infarct volume): slope of FIV per mmHg decrease was -0.29 mL (futility P=0.99).
- Functional outcomes favored control (≤180 mmHg): mean utility-weighted mRS 0.58 vs 0.51 (<140) vs 0.47 (<160); median 90-day mRS 2 vs 3 vs 3.
- 24h NIHSS worse in lower-target groups: mean 7 (≤180) vs 11 (<140) vs 12 (<160); difference for <160 vs ≤180: +4.6 (95% CI 0.6-8.6).
- In-hospital mortality numerically higher in <160 group: 15% vs 7.5% in both other groups.
- Hemorrhage rates similar across all groups: any ICH 36%/32%/30%; sICH 5%/3%/5%.
- Predicted success for future trial: only 25% for <140 (at n=1,500) and 14% for <160 — dampening enthusiasm for large pivotal trial.
- BP separation achieved: 90th percentile SBP 139 (<140), 153 (<160), 157 (≤180) mmHg.
- Antihypertensive use markedly asymmetric: 72.5% (<140) vs 55% (<160) vs 25% (≤180).
- Consistent with ENCHANTED2/MT and OPTIMAL-BP: intensive BP lowering after EVT appears harmful or futile.
Study Design
- Study Type
- Pragmatic, multisite, randomized, open-label, futility design with blinded endpoint assessment (Phase 2)
- Randomization
- Yes
- Blinding
- Open-label treatment; blinded endpoint (neuroradiologist for imaging, certified rater for 90-day mRS). Permuted block randomization stratified by site.
- Sample Size
- 120
- Follow-up
- 90 days
- Centers
- 3
- Countries
- United States
Primary Outcome
Definition: Co-primary: (1) Follow-up infarct volume at 36h; (2) Utility-weighted mRS at 90 days. Futility design.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| ≤180: FIV 46.4 mL; UW-mRS 0.58 | <140: FIV 32.4 mL, UW-mRS 0.51. <160: FIV 50.7 mL, UW-mRS 0.47. | - (FIV slope: -0.29 (-0.81 to ∞). UW-mRS slope: -0.0019 (-∞ to 0.0017).) | FIV futility P=0.99. UW-mRS futility P=0.93. |
Limitations & Criticisms
- Small sample (n=120) at only 3 US centers — limited generalizability.
- Baseline imbalances: ≤180 group had lower NIHSS (14 vs 16-18), higher anticoagulant use, more M2 occlusions.
- Mean SBP similar between ≤180 and <160 groups (129 vs 130 mmHg) — reduced separation.
- Futility design — not powered to detect harm definitively.
- Nicardipine first-line not available globally.
- No BP targets >180 mmHg tested.
- Infarct volume mediates only ~12% of EVT effect on outcomes.
Citation
JAMA. 2023;330(9):821-831.