TRUTH
(2024)Objective
To compare 90-day functional outcomes between an active IV antihypertensive blood-pressure-lowering strategy and a conservative non-lowering strategy in acute ischemic stroke patients with BP >185/110 mmHg as the sole contraindication to IVT.
Study Summary
• Despite higher IVT rates (94% vs 52%, p<0.0001) and shorter door-to-needle time (35 vs 47 min, p<0.0001), the functional advantage of more thrombolysis was offset by potential harms of rapid BP reduction
• Symptomatic ICH was similar between groups (5% vs 3%, aOR 1.28, 95% CI 0.62–2.62, p=0.24)
Intervention
IV labetalol (10 mg boluses ± continuous infusion) or IV nicardipine to lower BP <185/110 mmHg before IVT, versus conservative non-lowering strategy (IVT only if BP drops spontaneously below threshold)
Inclusion Criteria
Adults ≥18 years with acute ischemic stroke and BP >185/110 mmHg as the sole contraindication to IVT, otherwise fully eligible for thrombolysis
Study Design
Arms: Active BP lowering (n=853) vs No BP lowering (n=199)
Patients per Arm: 853 active BP lowering, 199 no BP lowering (1052 total from 37 Dutch stroke centres)
Outcome
• Unfavourable outcome (mRS 2–6): 66% vs 59% (aOR 1.34, 95% CI 0.91–1.97)
• Death or dependency (mRS 3–6): 39% vs 33% (aOR 1.38, 95% CI 0.84–2.25)
Bottom Line
Active IV antihypertensive BP lowering to enable IVT did not improve 90-day functional outcomes versus a conservative non-lowering strategy, despite dramatically higher IVT rates and shorter door-to-needle times — suggesting current guideline recommendations for this practice need reconsideration pending RCT evidence.
Major Points
- Active BP lowering did not improve 90-day functional outcomes vs no BP lowering (aOR 1.27, 95% CI 0.96-1.68), with the trend favouring the non-lowering strategy
- Active BP lowering dramatically increased IVT rates (94% vs 52%) and shortened door-to-needle time (35 vs 47 min), yet this did not translate to better outcomes
- Symptomatic ICH rates were similar between groups (5% vs 3%, aOR 1.28, 95% CI 0.62-2.62, p=0.24)
- Results were consistent across all sensitivity analyses and prespecified subgroups (age, sex, NIHSS severity)
- Study was underpowered (1052 vs 1235 planned) due to COVID-19 and funding cessation, increasing risk of type II error
- Findings align with prior trials showing no benefit or potential harm from BP lowering in acute stroke (RIGHT-2, MR ASAP, ENCHANTED, OPTIMAL-BP)
- An RCT is urgently needed — this observational design cannot fully exclude residual confounding despite cluster-based design and extensive covariate adjustment
Study Design
- Study Type
- Prospective, observational, cluster-based, parallel-group study
- Randomization
- No
- Blinding
- Outcome assessors (trained research nurses conducting 90-day telephone interviews) were masked to treatment centre and strategy
- Sample Size
- 1052
- Follow-up
- 90 days (completed April 5, 2022; data finalised Aug 15, 2022)
- Centers
- 37
- Countries
- Netherlands
Primary Outcome
Definition: 90-day functional status measured by modified Rankin Scale (mRS) ordinal shift (shift towards worse outcome)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| No BP lowering (n=198 analyzable; 1 missing) | Active BP lowering (n=839 analyzable; 14 missing) | 1.27 (0.96-1.68) | 0.098 |
Limitations & Criticisms
- Non-randomized observational design — residual confounding cannot be fully excluded despite cluster-based design and extensive covariate adjustment
- Underpowered — only 1052 of 1235 planned patients enrolled due to COVID-19 pandemic and funding cessation; increased risk of type II error
- Baseline imbalances despite adjustment: active group had more hypercholesterolaemia (35% vs 25%, p=0.0049), prior stroke/TIA (39% vs 31%, p=0.039), and antiplatelet use (38% vs 30%, p=0.029)
- Non-consecutive patient inclusion during COVID-19 pandemic raises potential selection bias, though comparison with non-included patients showed no significant baseline differences
- 22% of 90-day mRS scores derived from DASA registry rather than central telephone interview, though sensitivity analysis excluding these showed similar results
- No standardised follow-up brain imaging mandated — sICH rate may be underestimated
- Only 10 non-lowering centres (vs 27 active) — imbalanced clusters limit precision of the no-lowering estimate
- Cannot determine optimal BP target, timing, or agent for pre-IVT BP management from this observational design
Citation
Lancet Neurol 2024; 23: 807-15