The Lancet July 18, 2026

Efficacy and safety of tirofiban after successful endovascular reperfusion in acute ischaemic stroke (ATTRACTION) in China: a multicentre, double-blind, randomised controlled trial

Hao Huang, Shabei Xu, Tingting Qin, Minghuan Wang, Guo Li, Chenchen Liu, Gang Deng, et al. (ATTRACTION Investigators)

Bottom Line

In patients with acute ischemic stroke who achieved successful macroscopic endovascular reperfusion, adjunctive tirofiban significantly improved the likelihood of functional independence at 90 days without a statistically significant increase in symptomatic intracranial hemorrhage.

Key Findings

1. Tirofiban significantly increased the proportion of patients achieving functional independence (mRS 0-2) at 90 days compared to placebo (49.3% vs. 43.3%; adjusted RR 1.15, 95% CI 1.03-1.27; p=0.01).

2. The rate of symptomatic intracranial hemorrhage (sICH) within 48 hours was numerically higher in the tirofiban group but the difference was not statistically significant (11.9% vs. 9.4%; adjusted RR 1.24, 95% CI 0.91-1.68; p=0.17).

3. Mortality at 90 days was comparable between the tirofiban and placebo groups (18.3% vs. 19.0%; adjusted HR 0.96, 95% CI 0.75-1.22; p=0.72).

Study Design

Design

RCT

Double-Blind

Sample

1,380

Patients

Duration

90 days

Median

Setting

Multicenter, China

Population Patients with acute anterior-circulation large vessel occlusion (LVO) ischemic stroke who achieved successful endovascular recanalization (modified Thrombolysis In Cerebral Infarction [mTICI] score 2b-3).

Intervention Adjunctive tirofiban (an intra-arterial bolus followed immediately by a continuous 24-hour intravenous infusion).

Comparator Matching placebo (intra-arterial bolus followed by a 24-hour intravenous infusion).

Outcome Proportion of participants achieving functional independence at 90 days, defined as a modified Rankin Scale (mRS) score of 0 to 2.

Study Limitations

• The trial was conducted exclusively in a Chinese population across 82 centers, potentially limiting the generalizability of the findings to other ethnic groups and global stroke care systems with different periprocedural protocols.

• Although not statistically significant, the numerically higher rate of symptomatic intracranial hemorrhage in the tirofiban arm highlights the need for careful risk stratification and individualized safety-benefit weighing.

• The specific dosing protocol (intra-arterial bolus followed by a 24-hour intravenous infusion) means the results may not apply to other administration routes, dosing strategies, or different glycoprotein IIb/IIIa inhibitors.

Clinical Significance

The ATTRACTION trial provides pivotal, high-quality evidence that targeting microvascular impairment with a glycoprotein IIb/IIIa inhibitor (tirofiban) post-recanalization can yield meaningful clinical benefits. For patients with large vessel occlusion who achieve successful recanalization (mTICI 2b-3) following endovascular thrombectomy, the addition of tirofiban improves the odds of a good functional recovery. Clinically, it arms stroke neurologists and neurointerventionalists with an adjunctive pharmacological tool to combat the 'no-reflow' phenomenon, provided patients are carefully screened to minimize bleeding risks.

Historical Context

Over the past decade, endovascular thrombectomy (EVT) has become the gold standard for acute anterior-circulation large vessel occlusion (LVO) stroke, dramatically improving outcomes. However, a persistent clinical challenge remained: up to half of patients who achieve excellent macroscopic angiographic recanalization still fail to attain functional independence. This discrepancy is widely hypothesized to result from microvascular incomplete reperfusion, or 'no-reflow', driven by distal microthrombi, endothelial injury, and platelet aggregation. Prior trials (such as RESCUE BT in 2022) investigated intravenous tirofiban administered before or during EVT, which yielded mixed efficacy results. ATTRACTION specifically targeted the post-recanalization window—hypothesizing that once the macrovascular clot is cleared, antiplatelet therapy could optimize microvascular flow. By demonstrating improved functional outcomes with post-EVT tirofiban, ATTRACTION shifts the paradigm toward combined mechanical and microvascular pharmacological rescue strategies in modern stroke care.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

What is the mechanism of action of tirofiban, and why might administering this antiplatelet agent be beneficial after mechanical thrombectomy has already successfully restored blood flow in an acute ischemic stroke?

Key Response

Tirofiban is a reversible glycoprotein IIb/IIIa receptor antagonist that inhibits platelet aggregation. Even after macroscopic recanalization (eTICI 2b/3), microvascular thrombosis, endothelial injury from the stent retriever/aspiration catheter, and downstream micro-emboli can impair distal tissue perfusion (the 'no-reflow' phenomenon). Tirofiban helps prevent secondary micro-thrombosis and reocclusion, preserving the penumbra.

Resident

If a patient achieves successful reperfusion following mechanical thrombectomy for a large vessel occlusion, how does the addition of tirofiban affect their post-procedural risk profile, particularly regarding the feared complication of symptomatic intracranial hemorrhage (sICH)?

Key Response

Historically, antiplatelets post-stroke intervention carried high bleeding risks. However, the ATTRACTION trial demonstrated that adjunctive tirofiban significantly improved the odds of 90-day functional independence without a statistically significant increase in sICH. Residents must learn to balance this efficacy with individual patient risk factors, such as blood pressure control and infarct core size, when managing post-EVT patients.

Fellow

The ATTRACTION trial focuses on patients with successful macroscopic reperfusion. How might the underlying stroke etiology (intracranial atherosclerotic disease vs. cardioembolism) influence the efficacy and safety profile of post-EVT tirofiban, and why is this distinction critical for neurointerventionalists?

Key Response

Cardioembolic strokes typically lack underlying vessel stenosis, whereas intracranial atherosclerotic disease (ICAD) involves in-situ plaque rupture and severe local endothelial injury. ICAD has a high tendency for immediate reocclusion post-thrombectomy. Tirofiban is mechanistically ideal for stabilizing this irritable endothelium in ICAD, which is highly prevalent in Asian populations. Fellows must consider how etiology drives the need for adjuvant antiplatelets.

Attending

Historically, standard practice dictated avoiding systemic antithrombotics for 24 hours following acute stroke interventions to minimize hemorrhagic transformation. How should the results of the ATTRACTION trial prompt us to reevaluate our institutional post-EVT protocols?

Key Response

This trial challenges the '24-hour no antithrombotic' dogma by showing that a targeted, short-acting IV antiplatelet (tirofiban) improves outcomes without severe sICH penalties in selected patients. Attendings must decide whether to adopt this into standard stroke pathways now or await confirmatory Western trials, carefully weighing the potential paradigm shift in post-reperfusion medical management.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

The ATTRACTION trial was conducted entirely in China, a population with a disproportionately high prevalence of intracranial atherosclerotic disease (ICAD). How does this epidemiological factor threaten the external validity of the trial, and what trial design modifications would be necessary to replicate this study in a predominantly Caucasian population?

Key Response

The benefit of tirofiban may be heavily driven by the ICAD subgroup, where antiplatelets effectively prevent in-situ reocclusion. In Western populations, large vessel occlusions are more frequently cardioembolic. A rigorous replication trial must formally stratify randomization by TOAST criteria (stroke etiology) and quantify the interaction effect between stroke subtype and tirofiban efficacy to ensure the results are generalizable.

Journal Editor

When critically appraising the ATTRACTION trial, how robust is the blinding and standardization of concurrent medical management, and what specific methodological threats to validity would you scrutinize regarding the primary outcome assessment?

Key Response

Given that post-EVT care (e.g., blood pressure parameters, ICU management) can vary, a rigorous reviewer would scrutinize whether concurrent therapies were strictly standardized. Furthermore, the modified Rankin Scale (mRS) at 90 days has subjective elements; if assessors were unblinded by minor bleeding events or different clinical courses, detection bias could inflate the treatment effect size. The precise definition of sICH used must also be carefully validated.

Guideline Committee

Current AHA/ASA stroke guidelines do not routinely recommend adjuvant glycoprotein IIb/IIIa inhibitors post-EVT due to historically conflicting data. Based on the ATTRACTION trial, what specific Class of Recommendation and Level of Evidence should be proposed for post-EVT tirofiban, and what caveats must be included?

Key Response

Current guidelines caution against antiplatelet use within 24 hours of IV thrombolysis. ATTRACTION provides Level B-R (Randomized) evidence suggesting benefit. The committee might consider introducing a Class IIb (weak) recommendation for adjunctive tirofiban in patients with successful reperfusion (particularly those with suspected ICAD), emphasizing caveats such as strict blood pressure control, exclusion of large infarct cores, and careful monitoring for hemorrhagic transformation.

Clinical Landscape

Noteworthy Related Trials

2015

MR CLEAN

n = 500 · NEJM

Tested

Endovascular therapy (intraarterial treatment) plus usual care

Population

Patients with acute ischemic stroke caused by proximal anterior circulation occlusion within 6 hours

Comparator

Usual care alone

Endpoint

Modified Rankin Scale (mRS) score at 90 days

Key result: Endovascular therapy significantly improved the rate of functional independence at 90 days compared to usual care.

2022

RESCUE BT

n = 948 · JAMA

Tested

Intravenous tirofiban before and during EVT

Population

Acute ischemic stroke patients with large vessel occlusion undergoing EVT

Comparator

Placebo

Endpoint

Modified Rankin Scale (mRS) score at 90 days

Key result: Tirofiban did not significantly improve functional outcomes compared to placebo and increased the risk of symptomatic intracranial hemorrhage.

2022

CHOICE

n = 121 · JAMA

Tested

Adjunctive intra-arterial alteplase

Population

Patients with acute ischemic stroke and successful reperfusion after thrombectomy

Comparator

Placebo

Endpoint

Excellent functional outcome (mRS 0-1) at 90 days

Key result: Adjunctive intra-arterial alteplase after successful thrombectomy increased the likelihood of an excellent functional outcome at 90 days.

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