Sue Hughes
Intravenous (IV) administration of the antiplatelet agent tirofiban for 72 hours was associated with a reduction in early neurologic deterioration compared with oral aspirin therapy in patients with acute ischemic stroke, in the randomized TREND trial.
The results were presented at the International Stroke Conference 2024, held on February 7-9 in Phoenix, Arizona.
Lead author Zhao Wenbo, MD, Xuanwu Hospital, Beijing, China, noted that neurologic deterioration, characterized by a sudden onset and quick peak of neurologic deficits, is a common phenomenon in acute ischemic stroke and is strongly associated with poor clinical outcomes.
Ischemic stroke progression is the main cause of neurologic deterioration, especially during the first few days after onset, Wenbo said. Several clinical studies have found that intensive antiplatelet therapy may prevent early neurologic deterioration and improve functional outcomes, but administering oral antiplatelet agents can be difficult because of dysphagia, he reported.
The TREND trial was conducted to investigate whether IV tirofiban could prevent early neurologic deterioration without increasing the risk for symptomatic intracerebral hemorrhage in acute ischemic stroke.
The study included 426 patients with acute ischemic stroke within 24 hours of symptom onset who had a neurologic deficit attributed to focal cerebral ischemia and a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20 points and who were not treated with thrombolysis or endovascular thrombectomy. Patients with cardioembolic stroke were also excluded.
Patients were a median of 10-12 hours from symptom onset and had a baseline NIHSS score of 5.
They were randomized to IV tirofiban or oral aspirin for 72 hours. All patients were then continued on oral antiplatelet therapy.
The primary efficacy outcome was neurologic deterioration within 72 hours after randomization, defined as an increase in NIHSS score of 4 points or more.
This occurred in nine patients (4.2%) in the tirofiban group vs 28 (13.2%) in the control group (relative risk, 0.32; 95% CI, 0.15-0.66; P = .002).
A consistent benefit of IV tirofiban was seen across all subgroups.
The secondary endpoint of neurologic deterioration within 72 hours after randomization, defined as an increase of NIHSS score of 2 points or more, was also significantly reduced. This occurred in 11.7% of the tirofiban group vs 23.6% of the aspirin group (RR, 0.49; 95% CI, 0.32-0.75; P = .001).
An excellent outcome on the modified Rankin Scale (mRS) disability score (mRS, 0-1) at 90 days was seen in 75% of tirofiban vs 68% of aspirin patients, a nonsignificant difference.
A good outcome (mRS, 0-2) occurred in 89% of tirofiban vs 86% of aspirin patients, again a nonsignificant difference.
There were no symptomatic intracerebral hemorrhages within 72 hours after randomization (the primary safety endpoint) in either group, and the incidence of systemic bleeding also did not differ significantly between the groups.
Wenbo concluded that further randomized clinical trials are needed to determine the efficacy of tirofiban on functional outcomes.
‘Promising Results’
Commenting on the study for theheart.org | Medscape Cardiology, conference chair, Tudor Jovin, MD, Cooper Medical School of Rowan University, Camden, New Jersey, and vice-chair, Lauren Sansing, MD, Yale School of Medicine, New Haven, Connecticut, both said they thought the results were promising.
“This study didn’t show any long-term outcome benefit, but this was a smaller study, and the results need to be replicated in a larger study with sufficient power to look at longer-term outcomes,” Sansing noted. “But we don’t have anything better than aspirin at present for these patients, so it’s exciting that there may be something in the pipeline for this group.”
Jovin pointed out that the TREND trial selected patients on the cause of their stroke, in line with the practice of precision medicine.
“By excluding patients who received thrombolysis or thrombectomy and those who had cardioembolic strokes, we are left with a population who we don’t have many treatment options for,” he said. “These are patients with smaller or moderate strokes who may arrive too late for thrombolysis. It would be great to be able to do something more than just aspirin for these patients.”
Jovin noted that the study was underpowered to show long-term benefits, but there were some promising trends.
“It stands to reason that if neurologic function does not get worse in the early hours and days after stroke, then the long-term outcomes are likely to be better,” he noted. “But this needs to be confirmed in larger trials.”
Interestingly, another study, the MOST trial, also presented at the ISC-24 meeting, showed no benefit with the IV antithrombotic agents argatroban or eptifibatide on 90-day functional outcomes when added to thrombolysis in acute ischemic stroke.
Jovin pointed out that the MOST and TREND trials included different populations of patients — the MOST patients received thrombolysis, while the TREND patients did not. And in the MOST trial, about half the patients had a large vessel occlusion and underwent thrombectomy, whereas these patients were excluded in TREND.
Sansing added that patients in the TREND trial may have had small vessel disease or other atherosclerotic disease, or strokes due to the narrowing of vessels or due to an unknown cause. They were also given 3 days of IV tirofiban, whereas the duration of antithrombotic treatment in MOST was shorter.
The TREND study was funded by the National Key Research and Development Program of China, the National Science Foundation of Beijing Municipality, and the Beijing Municipal Science and Technology Commission
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