Tirofiban a Better Option for Ischemic Stroke When Lytics and Thrombectomy Aren’t?

PHOENIX — For acute ischemic stroke patients without thrombolytic or thrombectomy options, tirofiban was better than aspirin alone, the TREND trial showed.

In non-cardioembolic stroke, starting tirofiban within 24 hours of symptom onset reduced the incidence of neurological deterioration within 72 hours to 4.2%, compared with 13.2% with aspirin (RR 0.32, 95% CI 0.16-0.65).

Functional outcomes at 90 days were similar between groups as a secondary endpoint, Wenbo Zhao, MD, of Xuanwu Hospital at Capital Medical University in Beijing, reported at the American Stroke Association’s International Stroke Conference.

However, Larry B. Goldstein, MD, chair of neurology at the University of Kentucky in Lexington, questioned whether the data really drive the field forward.

“We know that the addition of a second antiplatelet drug to aspirin at least reduces the risk of recurrent stroke,” he told MedPage Today. “So I don’t quite understand why, given all of the other data — a lot of it coming from China, actually, where they’ve shown that dual antiplatelet therapy was more efficacious than monotherapy with aspirin — why it was a monotherapy with aspirin comparator.”

Given how many patients fit in this category with contraindications to IV thrombolytics and without the anatomical occlusion location that benefits from mechanical thrombectomy, Goldstein suggested that a trial should compare the usual dual antiplatelet combination of clopidogrel and aspirin against tirofiban with aspirin.

The trial follows the RESCUE BT2 trial in which tirofiban also proved superior to aspirin for what those researchers called “heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels.”

An editorial accompanying that paper in the New England Journal of Medicine noted that the efficacy and safety of the dual antiplatelet approach “has been shown mainly in patients with mild strokes or high-risk transient ischemic attacks. The benefits and safety of more aggressive antiplatelet therapy in patients with moderate-to-severe stroke have not been established.”

The editorial suggested that the RESCUE BT2 results “open the door to reconsidering glycoprotein IIb/IIIa receptor inhibitors in acute ischemic stroke” but called for confirmation of the findings.

TREND aimed to fill that role, enrolling 426 patients in China who were age 18-80 with presumed non-cardioembolic ischemic stroke (NIH Stroke Scale [NIHSS] score 4-20) within 24 hours of last known well or symptom onset who were not treated with IV thrombolysis or endovascular thrombectomy.

Participants were randomly assigned to open-label IV tirofiban or aspirin at 150-300 mg/day for 72 hours followed by aspirin alone or with clopidogrel. Randomization was stratified by age, infarct location, and pre-existing antiplatelet medication use. Blinded assessment included neurological deterioration of at least 4 points on the NIHSS at 72 hours as the primary endpoint.

All subgroup analyses supported tirofiban as better for that endpoint.

A lower bar for neurological deterioration — an NIHSS increase of ≥2 — yielded similar results as well, with a rate of 11.7% versus 23.6% (RR 0.49, 95% CI 0.32-0.75).

Although the modified Rankin Scale score averaged 1 in both groups, the researchers called for further studies powered for clinical outcomes to determine efficacy of tirofiban for functional endpoints.

In terms of safety, no cases of symptomatic intracerebral hemorrhage or severe bleeding occurred, and mortality was similar between groups.

The editorial for RESCUE BT2 noted the high prevalence of intracranial arterial narrowing (48%), “presumably atherosclerotic, which may limit the generalizability of the trial results to non-Chinese populations.” In TREND, large artery atherosclerosis was the etiology for 23.4% of the tirofiban group and 30.7% of the aspirin group.

Goldstein noted that future studies with a broader population outside of China would be helpful, “although the other studies that have been done in China have translated to a more general population.”

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