PDF: ASSET-IT
(2025)Objective
To assess the efficacy and safety of early tirofiban administration after intravenous thrombolysis in patients with acute ischemic noncardioembolic stroke not eligible for thrombectomy
Study Summary
• Increased symptomatic ICH with tirofiban (1.7% vs 0%) but similar mortality (4.1% vs 3.8%)
• NNT of approximately 9 for mRS 0-1
Intervention
Tirofiban IV infusion (0.4 µg/kg bolus for 30 min, then 0.1 µg/kg/min maintenance for 23.5 hours) started within 60 minutes after IVT completion vs placebo
Inclusion Criteria
Adults ≥18 years with acute ischemic noncardioembolic stroke, NIHSS 4-25, received IVT within 4.5 hours of onset, randomized within 55 minutes after IVT completion, not eligible for thrombectomy, pre-stroke mRS ≤1
Study Design
Arms: Tirofiban 24-hour IV infusion vs Placebo
Patients per Arm: Tirofiban: 414, Placebo: 418
Outcome
• mRS 0-2 at 90 days: 80.4% vs 72.7%
• Symptomatic ICH: 1.7% vs 0%
Bottom Line
In patients with mild-to-moderate noncardioembolic ischemic stroke treated with IVT within 4.5 hours, early tirofiban administration within 1 hour of thrombolysis completion significantly increased excellent functional outcomes at 90 days (65.9% vs 54.9%, NNT ~9), with a small increase in symptomatic ICH (1.7% vs 0%) but no difference in mortality.
Major Points
- Phase 3 double-blind RCT of 832 patients at 38 centers in China
- Tirofiban significantly increased mRS 0-1 at 90 days: 65.9% vs 54.9% (RR 1.20, 95% CI 1.07-1.34, p=0.001)
- Functional independence (mRS 0-2) also improved: 80.4% vs 72.7%
- Symptomatic ICH occurred in 1.7% with tirofiban vs 0% with placebo
- Mortality similar between groups: 4.1% vs 3.8%
- Benefit observed across subgroups including age, stroke severity, and thrombolytic agent type
- Greater benefit seen in patients with NIHSS ≥8 (RR 1.54) and ASPECTS ≤8 (RR 1.41)
- Predominantly large-artery atherosclerosis etiology (58%) - excluded cardioembolic strokes
- Tirofiban administered within median 44 minutes after IVT completion
Study Design
- Study Type
- Phase 3, multicenter, double-blind, randomized, placebo-controlled trial
- Randomization
- Yes
- Blinding
- Double-blind (all trial personnel and patients unaware of group assignments); outcome adjudication by independent blinded committee
- Sample Size
- 832
- Follow-up
- 90 days
- Centers
- 38
- Countries
- China
Primary Outcome
Definition: Excellent functional outcome defined as mRS score 0-1 at 90 days, adjudicated by trained central evaluators blinded to treatment allocation
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 229/417 (54.9%) | 273/414 (65.9%) | - (1.07-1.34) | 0.001 |
Limitations & Criticisms
- Conducted exclusively in China with predominantly large-artery atherosclerosis etiology (58%), limiting generalizability to Western populations where cardioembolic stroke is more common
- Excluded patients with atrial fibrillation/cardioembolic stroke - limits applicability to a significant stroke population
- Relatively mild stroke severity (median NIHSS 6) - may not generalize to more severe strokes
- Symptomatic ICH occurred only in tirofiban group (1.7% vs 0%) - safety signal despite low absolute rate
- SITS-MOST criteria for sICH assessed only within 36 hours - may have missed late hemorrhages
- Lack of systematic vascular imaging before and after treatment limits assessment of recanalization/reocclusion
- Reasons for not performing thrombectomy in patients with LVO not systematically recorded
- High proportion with prior stroke (27.6%) may affect generalizability
- Substantial proportion of eligible patients declined participation - potential selection bias
- Secondary outcomes not adjusted for multiplicity - no conclusions can be drawn from these
- Brant test indicated violation of proportional odds assumption for mRS shift analysis
Citation
N Engl J Med 2025;393:1191-201