RESCUE BT2
Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion
Year of Publication: 2023
Authors: W. Zi, J. Song, W. Kong, ..., and Q. Yang
Journal: The New England Journal of Medicine
Citation: N Engl J Med 2023;388:2025-36.
PDF: Clinical Question
In patients with acute ischemic stroke who have no occlusion of large or medium-sized vessels, is intravenous tirofiban more effective than oral aspirin for improving functional outcomes?
Bottom Line
In patients with acute ischemic stroke without large or medium-sized vessel occlusion, intravenous tirofiban was associated with a greater likelihood of excellent functional outcome at 90 days compared to oral aspirin. However, this was accompanied by a slightly higher incidence of symptomatic intracranial hemorrhage.
Major Points
- RESCUE BT2 was a multicenter, randomized, double-blind, double-dummy trial conducted in China comparing intravenous tirofiban to oral aspirin in patients with acute ischemic stroke without large or medium-sized vessel occlusion.
- The primary endpoint was an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 or 1.
- Tirofiban significantly improved the rate of excellent outcome versus aspirin (29.1% vs. 22.2%; adjusted risk ratio 1.26; P=0.02).
- The global outcome at 90 days was also improved with tirofiban (adjusted common odds ratio 1.38; P=0.01), but other secondary outcomes were not statistically significant after hierarchical testing.
- Symptomatic intracranial hemorrhage was more frequent in the tirofiban group (1.0% vs. 0%, P=0.03).
Design
Study Type: Multicenter, double-blind, double-dummy, randomized clinical trial.
Randomization: 1
Blinding: Double-blind, double-dummy.
Enrollment Period: October 20, 2020, through June 30, 2022.
Follow-up Duration: 90 days.
Centers: 117
Countries: China
Sample Size: 1177
Analysis: Modified intention-to-treat; risk ratios estimated using modified Poisson regression with adjustment for age, baseline NIHSS, thrombolysis status, and time to randomization.
Inclusion Criteria
- Age ≥18 years
- Acute ischemic stroke with NIHSS score ≥5 and at least one limb with motor item score 2–4
- No visible large or medium-sized intracranial vessel occlusion on CTA, MRA, or DSA
- One of four clinical scenarios: (1) ineligible for reperfusion <24h; (2) progression 24–96h; (3) early deterioration after IVT; (4) no improvement after IVT
Exclusion Criteria
- Imaging-confirmed intracranial hemorrhage
- Any definite source of cardiac embolism
- Prestroke modified Rankin Scale score ≥2
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| Median age (IQR) - yr | 68.0 (59.0–76.0) | 68.0 (58.0–75.0) |
| Male sex no. (%) | 373 (65.3) | 379 (62.5) |
| Hypertension - no. (%) | 381 (66.7) | 375 (61.9) |
| Diabetes mellitus - no. (%) | 167 (29.2) | 162 (26.7) |
| Cerebral infarction (history) - no. (%) | 83 (14.5) | 96 (15.8) |
| Median NIHSS score (IQR) | 9.0 (7.0–10.0) | 9.0 (7.0–10.0) |
| Median ASPECTS (IQR) | 9.0 (9.0–10.0) | 9.0 (9.0–10.0) |
| Presentation type (Ineligible for reperfusion <24hr) - no. (%) | 318 (55.7) | 332 (54.8) |
| Localization (Anterior circulation) - no. (%) | 456 (79.9) | 489 (80.7) |
| Presumed mechanism (Penetrating artery disease) - no./total no. (%) | 417/566 (73.7) | 438/601 (72.9) |
Arms
| Field | Control | Tirofiban |
|---|---|---|
| Intervention | Oral aspirin (100 mg per day) + intravenous placebo for 2 days, followed by open-label aspirin 100 mg daily to day 90. | Intravenous tirofiban (0.4 µg/kg/min for 30 min, then 0.1 µg/kg/min for up to 48h) + oral placebo for 2 days, followed by open-label aspirin 100 mg daily to day 90. |
| Duration | 90 days | 90 days |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Excellent outcome (mRS 0–1) at 90 days. | Primary | 22.2% (126/567) | 29.1% (176/604) | 1.26 | 0.02 |
| Global outcome at 90 days (composite of mRS 0–1, NIHSS 0–1, Barthel Index 95–100, Glasgow Outcome Scale 5) | Secondary | 1.38 (95% CI, 1.07–1.78) | 0.01 | ||
| Shift in mRS distribution at 90 days | Secondary | Median mRS 2 (IQR 2–3) | Median mRS 2 (IQR 1–3) | 1.23 (95% CI, 1.00–1.51) | 0.06 |
| Functional independence (mRS 0–2) at 90 days | Secondary | 56.4% (320/567) | 62.1% (375/604) | 1.07 (95% CI, 0.98–1.16) | Not significant |
| Death at 90 days | Adverse | 2.6% (15/567) | 3.8% (23/604) | 1.62 (95% CI, 0.88–2.95) | 0.12 |
| Symptomatic intracranial hemorrhage within 48 hours | Adverse | 0% | 1.0% (6/606) | 0.03 | |
| Serious adverse event | Adverse | 13.0% (74/571) | 16.0% (97/606) | 0.14 |
Subgroup Analysis
Subgroup analyses did not reveal any significant treatment effect heterogeneity. See Supplementary Appendix for details.
Criticisms
- Heterogeneous population with four different clinical presentations.
- Only a small subset of patients received IV thrombolysis before enrollment.
- Lower than expected rate of excellent outcomes in both arms may reflect care quality or population differences.
- Follow-up imaging was not mandated unless neurologic deterioration occurred, limiting detection of asymptomatic hemorrhages.
Funding
National Natural Science Foundation of China (Major Program, project number 82090040)
Based on: RESCUE BT2 (The New England Journal of Medicine, 2023)
Authors: W. Zi, J. Song, W. Kong, ..., and Q. Yang
Citation: N Engl J Med 2023;388:2025-36.
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