Tirofiban may improve outcomes in LAA strokes

While additional tirofiban prior to endovascular treatment (EVT) did not appear to benefit stroke patients with large vessel occlusion (LVO), it did seem to have an advantage for those with large artery atherosclerosis (LAA), findings from the RESCUE BT trial have shown.

“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr Raul Nogueira from the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, US, during his presentation at ISC 2022’s Opening Main Event.

At 90 days, modified Rankin Scale (mRS) scores were similar in both tirofiban and placebo arms (mRS, 3 for both; adjusted common odds ratio (OR), 1.09; p=0.46). A modest treatment effect was also observed in the key secondary endpoint of mRS score of 0 to 1 or return to premorbid mRS (adjusted common OR, 1.22). [ISC 2022, abstract LB2]

However, treatment effect modification by stroke aetiology was detected for LAA, Nogueira noted, as seen on subgroup analysis wherein tirofiban seemed favourable for those with LAA as opposed to non-LAA patients (adjusted common OR, 1.43). “[This is] an important signal. The subgroup with atherosclerotic disease seems to benefit from tirofiban,” he pointed out.

Potential safety concerns

Excess bleeding rates were higher with tirofiban vs placebo (34.9 percent vs 28.0 percent; p=0.02 [any ICH*] and 9.7 percent vs 6.4 percent; p=0.06 [symptomatic ICH]). Nonetheless, there was no difference between tirofiban and placebo in terms of 90-day mortality (18.1 percent vs 16.9 percent), clot migration (14.5 percent vs 14.9 percent), and distal occlusion present at the end of procedure (11.5 percent vs 10.3 percent).

Worth considering

About a third of stroke patients with LVO fail to achieve optimal reperfusion with EVT despite its reported benefit. [Stroke 2018;49:e46-e110] “Mechanical thrombectomy devices may cause endothelial denudation and vessel wall damage, potentially leading to thrombotic complications, which can consequently lead to vascular re-occlusion. [This] would obviously impact outcomes at 90 days,” said Nogueira.

“A potential strategy to improve outcomes would be to inhibit platelets. Tirofiban comes as a great candidate, being a nonpeptide glycoprotein IIb/IIIa receptor inhibitor that is highly selective, has a reversible action, very rapid onset of action, and a short half-life,” Nogueira continued.

The team evaluated patients (n=948; mean age 68 years, 59 percent male) with proximal intracranial LVOs within 24 hours of last known well across 55 centres in China. Participants were randomized 1:1 to receive IV tirofiban** or placebo prior to undergoing rapid EVT. Median NIHSS*** score was 16 while median baseline ASPECTS^# score was 8. LAA was the most frequent stroke aetiology (46 percent) followed by cardio-embolism (43 percent). About 65 percent had occlusion at the MCA^## M1 segment while 20 percent had intracranial ICA^## occlusion.

“[Our] results indicate that not all patients with LVO stroke should be treated with tirofiban. But in patients with LAA, tirofiban in combination with EVT may help further reduce the severity of disability,” said Nogueira.

“In conclusion, [our findings suggest that] tirofiban may improve EVT outcomes in LAA strokes. Clinicians who encounter LAA patients with LVO may consider treatment with tirofiban,” he concluded, calling for future trials to validate the findings.