ATTRACTION
Efficacy and safety of tirofiban after successful endovascular reperfusion in acute ischaemic stroke (ATTRACTION) in China: a multicentre, double-blind, randomised controlled trial
Clinical Question
Does adjunctive intra-arterial bolus plus 24-hour IV infusion of tirofiban after successful endovascular reperfusion improve 90-day functional independence in patients with acute ischaemic stroke from anterior-circulation large-vessel occlusion?
Bottom Line
In patients with acute ischaemic stroke due to anterior-circulation large-vessel occlusion who achieved successful reperfusion (mTICI 2b/3) after endovascular thrombectomy, adjunctive tirofiban (5 μg/kg IA bolus + 0.1 μg/kg/min IV for 24h) increased 90-day functional independence (49% vs 43%, adjusted RR 1.15) without a statistically significant increase in symptomatic intracranial haemorrhage, though sICH was numerically higher and bleeding risk warrants caution—especially in cardioembolic stroke.
Major Points
- Adjunctive tirofiban significantly increased 90-day functional independence (mRS 0-2): 49% vs 43% (adjusted RR 1.15, 95% CI 1.03-1.27, p=0.0092).
- Absolute risk difference favored tirofiban by 6.1 percentage points (95% CI 0.8-11.3, p=0.023).
- Excellent recovery (mRS 0-1) was more common with tirofiban (35% vs 30%; adjusted RR 1.20, 95% CI 1.04-1.37, p=0.012) and the ordinal mRS shift favored tirofiban (common OR 1.22, 95% CI 1.01-1.48, p=0.040).
- Symptomatic intracranial haemorrhage at 48h was numerically higher with tirofiban (12% vs 9%; adjusted RR 1.24, 95% CI 0.91-1.68, p=0.17) but not statistically significant.
- No significant difference in any ICH at 48h (34% vs 32%; RR 1.07, 95% CI 0.92-1.25, p=0.35) or 90-day mortality (18% vs 19%; HR 0.96, 95% CI 0.75-1.22, p=0.72).
- Exploratory subgroup analysis raised a possible safety concern in cardioembolic stroke patients.
- Conducted in a near-exclusively Han Chinese population (99%), limiting generalizability.
- Supports consideration of tirofiban as a post-reperfusion adjunctive strategy, with bleeding risk-benefit weighing.
Design
Study Type: Multicentre, double-blind, randomised, placebo-controlled trial
Randomization: 1
Blinding: Double-blind (patients, treating clinicians, investigators, and outcome assessors masked; identical-appearing study kits)
Allocation: 1:1 centralised web-based randomisation with permuted blocks of four, stratified by study site
Enrollment Period: April 9, 2024 to September 29, 2025
Follow-up Duration: 90 days
Centers: 82
Countries: China
Sample Size: 1380
Analyzed: 1380
Analysis: Intention-to-treat for efficacy; safety analyses in patients receiving study treatment with at least one safety evaluation
Power Calculation: 1360 patients (680 per group) required for 80% power at two-sided alpha 0.05, assuming an 8 percentage-point treatment effect and 10% loss to follow-up; no interim efficacy analyses
Registration: ClinicalTrials.gov NCT06265051
Inclusion Criteria
- Age ≥18 years
- Acute ischaemic stroke due to anterior-circulation large-vessel occlusion within 24 h from last known well
- NIHSS 6-30 immediately before enrolment
- Pre-stroke mRS 0 or 1
- Imaging-confirmed occlusion of intracranial ICA or M1/M2 segment of MCA
- ASPECTS ≥6 on baseline non-contrast CT or diffusion-weighted MRI
- Successful reperfusion (mTICI 2b or 3) documented after EVT, or spontaneous improvement to mTICI 2b-3 with no mechanical thrombectomy planned
- Written informed consent from patient or legally authorised representative
Exclusion Criteria
- Intra-arterial thrombolysis after the index stroke
- Receipt of tirofiban within 24 h before EVT
- Bleeding within 30 days before stroke onset
- Surgery within 14 days before stroke onset
- Planned use of antiplatelet therapy (including tirofiban) outside trial regimen during first 20 h after study therapy
- Intracranial haemorrhage on CT or MRI
- Midline shift, cerebral herniation, or mass effect with ventricular effacement
- Acute bilateral infarctions or multiple intracranial-vessel occlusions
- Isolated external carotid artery occlusion
Arms
| Field | Tirofiban | Control |
|---|---|---|
| N | 689 | 691 |
| Intervention | Tirofiban intra-arterial bolus 5 μg/kg (max 0.5 mg) delivered via catheter proximal to occlusion at 1 mL/min, followed by IV infusion 0.1 μg/kg/min for up to 24 h | Normal saline administered with identical volume and the same bolus and infusion procedures as tirofiban |
| Duration | 24 hours of infusion | 24 hours of infusion |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Functional independence (modified Rankin Scale score 0-2) | Primary | 299/691 (43%) | 340/689 (49%) | 1.15 | 0.023 (unadjusted); 0.0092 (adjusted) |
| Excellent functional outcome (mRS 0-1) at 90 days | Secondary | 205/691 (30%) | 242/689 (35%) | 0.012 | |
| Independent ambulation (mRS 0-3) at 90 days | Secondary | 424/691 (61%) | 436/689 (63%) | 0.37 | |
| Ordinal distribution of mRS at 90 days | Secondary | Median 3 (IQR 1-5) | Median 3 (IQR 1-5) | 0.040 | |
| Early neurological improvement at 36 h (NIHSS 0-1 or ≥4-point reduction) | Secondary | 427/691 (62%) | 426/689 (62%) | 0.89 | |
| Health-related quality of life (EQ-5D-5L) at 90 days | Secondary | Median 0.65 (IQR 0.06-0.96); 212 222/476 099 wins (44.6%) | Median 0.59 (IQR 0.06-0.96); 217 299/476 099 wins (45.6%) | 0.61 | |
| Symptomatic intracranial haemorrhage within 48 h | Safety | 65/691 (9%) | 82/687 (12%) | 0.17 | |
| Any intracranial haemorrhage on imaging within 48 h | Safety | 219/691 (32%) | 235/687 (34%) | 0.35 | |
| All-cause mortality within 90 days | Safety | 131/691 (19%) | 126/689 (18%) | 0.72 | |
| Adverse | 280/691 (41%) | 275/689 (40%) | |||
| Adverse | 176/691 (25%) | 152/689 (22%) | |||
| Adverse | 105/691 (15%) | 121/689 (18%) | |||
| Adverse | 60/691 (9%) | 43/689 (6%) |
Subgroup Analysis
Exploratory subgroup analyses raised a possible safety concern in patients with cardioembolic stroke, requiring cautious interpretation and further evaluation.
Criticisms
- Conducted exclusively in China with 99% Han Chinese population, limiting generalizability to other ethnic groups and healthcare systems.
- Symptomatic ICH was numerically higher in tirofiban group (12% vs 9%); although not statistically significant, the clinical relevance of this trend warrants caution.
- Possible safety concern in cardioembolic stroke subgroup may limit applicability in this important subpopulation.
- Tirofiban dosing regimen (IA bolus + 24h IV infusion) is more complex than simple oral antiplatelet strategies and may be harder to implement in some settings.
- Trial used a combined IA + IV route; results may not generalize to IV-only or other dosing regimens.
Funding
Tongji Hospital Clinical Research Fund (2024TJCR013)
Based on: ATTRACTION (The Lancet, 2026)
Authors: Huang H, Xu S, Qin T, ..., on behalf of the ATTRACTION Investigators
Citation: Huang H, et al. Lancet. Published online June 24, 2026. https://doi.org/10.1016/S0140-6736(26)00983-9
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