Tirofiban Superior to Aspirin in Stroke Without Large Occlusion

New research suggests some patients do better with tirofiban (Aggrastat) than with low-dose aspirin following disabling stroke without a visible large or medium intracranial vessel occlusion.

The study showed a greater percentage of such patients who received intravenous tirofiban had a modified Rankin Scale (mRS) score of 0-1 at 90 days compared with those who got low-dose oral aspirin.

The findings were presented by Wenjie Zi, Department of Neurology, Xinqiao Hospital and Second Affiliated Hospital, Amy Medical University, Chonqing, China, at the International Stroke Congress (ISC) 2023.

IV thrombolysis (IVT) is a proven treatment for patients with acute ischemic stroke within a narrow 4½ hour time window. Yet more than 50% of those who receive this treatment suffer neurologic deterioration or no neurologic improvement, and less than 10% of stroke patients can benefit from IVT, said Zi.

Endovascular treatment (EVT) is another proven therapy for stroke patients, but only for those with large or medium vessel occlusion, leaving up to 40% of stroke patients ineligible for EVT, said Zi.

No Proven Treatment

Many patients with small vessel stroke suffer disability, but there's currently no proven treatment for them "except early antithrombotic therapy for prevention purposes," he said.

Tirofiban is a highly selective fast-acting, non-peptide glycoprotein (GP) IIb/IIIa platelet receptor inhibitor that has a rapid onset of action and a short half-life (about 2 hours), said Zi. Research shows GP IIb/IIIa antagonists are effective for the treatment of acute coronary syndromes.

In stroke, the efficacy and safety of tirofiban has been investigated in two previous studies, but the SETIS trial was stopped early for lack of efficacy, and the SaTIS trial showed no beneficial effect on stroke outcomes. Zi and colleagues investigated the possibility that tirofiban would be effective for a more select group of patients.

The double-blind RESCUE-BT2 trial included 1177 adult patients across China with acute ischemic stroke without large or medium size occlusion determined by imaging, and a National Institutes of Health Stroke Scale (NIHSS) score of 5 or greater.

Eligible patients had to meet any of the following criteria: presenting within 24 hours of symptom onset and being ineligible for IVT or EVT; presenting more than 24 hours and less than 96 hours of symptom onset but within 24 hours of stroke progression; having been treated with IVT followed by early neurological deterioration or treated with IVT followed by no neurological improvement.

The study population had a median age of 68 years and 64% were male. The median baseline NIHSS score was 9.

Researchers randomly assigned patients to one of two groups: the tirofiban group or the aspirin group. The tirofiban group received an initial infusion of 0.4 μg/kg/minute for 30 minutes followed by a continuous infusion of 0.1 μg/kg/minute for up to 48 hours, plus oral placebo; the aspirin group received IV placebo and oral low-dose aspirin.

The primary endpoint was good outcome, defined as an mRS score of 0-1 at 90 days. About 29.1% of the tirofiban group and 22.2% of the aspirin group achieved this outcome (absolute difference of 6.9%; adjusted risk ratio [RR] 1.26; 95% CI, 1.04 - 1.53; P = .02).

A secondary outcome was mortality at 90 days; 3.81% of the tirofiban group and 2.65% of the aspirin group died during the study period (P = .12).

Only 0.99% of the tirofiban group and none in the aspirin group had a symptomatic intracranial hemorrhage (SICH) within 48 hours (P = .03), which was another secondary outcome. The result was similar for any imaging ICH.

"The rates of intracranial hemorrhage were low but slightly higher with tirofiban," noted Zi.

A limitation of the study was that it included only Asian patients. "Caution is warranted in generalizing the results to other populations," said Zi.

Very Important Study

Asked to comment, Tudor G. Jovin, MD, professor and chair, Department of Neurology, Cooper Medical School of Rowan University, Camden, New Jersey, said these new results are "very important" as tirofiban "is not routinely used" in patients with small vessel stroke who have severe deficits.

"We usually do pretty much nothing with these patients early on," said Jovin. He added this study raises the question of whether this is an appropriate strategy.

In the United States, tirofiban, but more frequently the "pretty much equivalent" GP IIb/IIIa inhibitor eptifibatide, is used more often in cardiology than neurology, noted Jovin.

The finding that tirofiban is effective in small vessel stroke patients is in some respects not surprising, he said. "This is a potent antiplatelet drug so it sort of makes sense to me."

The drug's short half-life is a plus for treating these patients, he said.

Also commenting on the study, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, noted the study was carried out in China where the rate of intracranial artery narrowing is higher than in other populations.

He stressed the findings need to be replicated, especially since "another trial, the SETIS trial with tirofiban in patients with acute ischemic stroke, was stopped early because of a lack of benefit."

The study received funding from Lunan Pharmaceutical Group Co., funded by National Natural Science Foundation of China. Zi, Jovin, and Goldstein report no relevant financial relationships.

International Stroke Conference 2023: Late breaking (LB) abstract #24. Presented February 10, 2023.

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