Tirofiban Plus Aspirin Fails to Reduce Early Neurological Deterioration in BAD-Related Stroke

A multicenter randomized clinical trial (NCT05310968) found that adding intravenous tirofiban to aspirin did not significantly reduce the risk of early neurological deterioration (END) or new stroke among patients with branch atheromatous disease (BAD)–related acute ischemic stroke. The combination was also not associated with an increased risk of moderate or severe bleeding, according to findings recently published online in JAMA Neurology.¹

The STRATEGY trial included 970 patients with BAD-related stroke treated within 48 hours of symptom onset across 38 hospitals in China. Participants were randomly assigned to receive either intravenous tirofiban plus aspirin or placebo plus aspirin, with the primary efficacy outcome defined as END within 7 days or new stroke within 90 days.

Overall, the primary end point occurred in 79 patients (17.1%) in the tirofiban-aspirin group compared with 89 patients (19.6%) in the placebo-aspirin group (HR, 0.88; 95% CI, 0.65-1.19; P = .39). Although the trial did not demonstrate a significant reduction in the primary outcome, an exploratory subgroup analysis suggested that patients with parent artery stenosis of at least 30% may derive greater benefit from tirofiban treatment. The investigators noted that this finding was not prespecified for interaction and requires external confirmation.

STRATEGY Evaluates Intensive Antiplatelet Therapy

BAD is an ischemic stroke subtype associated with a high risk of early neurological deterioration and recurrent events. It results from atherosclerotic or microatheromatous lesions involving the parent artery, with MRI typically showing a penetrating artery territory infarction. Despite its clinical relevance, BAD lacks standardized diagnostic criteria and has not been incorporated as a distinct category within the TOAST classification, complicating the development of targeted treatment strategies.¹

Tirofiban is a glycoprotein IIb/IIIa receptor antagonist with rapid onset of platelet inhibition and a relatively short half-life. Previous studies have suggested potential benefits of tirofiban in selected ischemic stroke populations, prompting investigators to examine whether short-term intensive antiplatelet therapy could prevent the early deterioration characteristic of BAD-related stroke.

The STRATEGY trial enrolled adults aged 18 to 80 years with acute ischemic stroke involving a single penetrating artery territory, less than 70% ipsilateral parent artery stenosis, and an NIHSS score of 10 or less. MRI confirmation was required, while patients with prior endovascular treatment or intravenous thrombolysis, intracranial hemorrhage, preexisting disability, or other specified exclusion factors were ineligible.

Patients were randomized to intravenous tirofiban or placebo, with all participants receiving aspirin through day 90. The double-blind, placebo-controlled trial included blinded outcome assessment and 90 days of follow-up.¹

Between November 2022 and November 2024, 970 of 1378 screened patients with suspected BAD-related stroke were randomized to tirofiban plus aspirin (n = 486) or placebo plus aspirin (n = 484). Participants had a median age of 63 years and baseline NIHSS score of 3; 62.6% were male and 97.3% were Han Chinese.¹

Primary Outcome Data

END or new stroke within 90 days occurred in 17.1% of patients receiving tirofiban plus aspirin and 19.6% of those receiving placebo plus aspirin, corresponding to an HR of 0.88 (95% CI, 0.65-1.19; P = .39). END within 7 days occurred in 14.6% and 16.1% of patients, respectively (RR, 0.91; 95% CI, 0.55-1.48; P = .70), while new stroke within 90 days occurred in 7.0% and 8.5%, respectively (HR, 0.85; 95% CI, 0.52-1.39; P = .52).¹

Other efficacy outcomes also generally showed no significant differences between groups. END or new stroke within 24 hours occurred in 12.6% of the tirofiban group and 14.5% of the placebo group (RR, 0.87; 95% CI, 0.57-1.31; P = .50). At 7 days, the corresponding rates were 14.6% and 16.3% (RR, 0.90; 95% CI, 0.54-1.47; P = .66). Composite vascular events through 90 days occurred in 8.2% and 9.1% of patients, respectively (HR, 0.94; 95% CI, 0.60-1.49; P = .80).

One secondary outcome did favor the tirofiban-aspirin group. Disability or death, defined as an mRS score of 2 to 6 at 90 days, occurred in 29.7% of patients receiving tirofiban compared with 35.3% receiving placebo (RR, 0.84; 95% CI, 0.73-0.97; P = .02). However, a post hoc ordinal analysis of the full mRS distribution did not reach statistical significance, with a common odds ratio of 0.82 (95% CI, 0.66-1.04).

The investigators also observed a trend toward a lower incidence of END in the tirofiban group during the first 24 hours after treatment, although the incidence became nearly identical between groups thereafter. Given tirofiban's rapid platelet inhibition, the authors suggested that the timing and duration of intensive antiplatelet treatment could warrant further investigation.

Subgroup Analysis Points to Parent Artery Stenosis

An exploratory subgroup analysis identified a potential treatment effect among patients with at least 30% parent artery stenosis. The authors noted that greater stenosis may reflect a heavier atherosclerotic burden, unstable plaques, and involvement of perforator artery origins, potentially creating a setting in which more intensive platelet inhibition could be beneficial.¹

However, the trial was not powered to draw definitive conclusions from subgroup analyses. The investigators also emphasized that no formal interactions between treatment assignment and the other prespecified subgroups—including age, sex, hypertension, diabetes, dyslipidemia, infarct diameter, infarct location, and baseline NIHSS score—were identified.

No Significant Increase in Bleeding

The safety findings did not identify a significant increase in moderate or severe bleeding with tirofiban. One patient (0.2%) in the tirofiban-aspirin group experienced a moderate or severe bleeding event compared with no patients in the placebo-aspirin group (P > .99). Symptomatic or asymptomatic intracranial hemorrhage occurred in 2 patients (0.4%) receiving tirofiban and none receiving placebo (P = .50).1

There were also no significant differences in vascular death or all-cause mortality. Overall adverse events occurred in 24.3% of the tirofiban group and 19.8% of the placebo group, while serious adverse events occurred in 3.5% and 2.9%, respectively.

The investigators concluded that intravenous tirofiban combined with aspirin did not significantly reduce END or new stroke compared with aspirin alone in patients with BAD-related stroke without severe parent artery stenosis. Although the treatment was associated with a lower rate of disability or death in a secondary analysis and appeared potentially beneficial in patients with greater parent artery stenosis, these findings require confirmation in future studies.

REFERENCES
1. Wang Y, Liao X, Feng S, et al. Tirofiban for branch atheromatous disease–related stroke: the STRATEGY randomized clinical trial. JAMA Neurol. Published online August 31, 2026. doi:10.1001/jamaneurol.2026.2855.