Tirofiban bests aspirin for disabling stroke without large, medium vessel occlusion

Findings from the RESCUE BT2 study support the potential of tirofiban to improve neurologic outcomes than aspirin in patients with acute ischaemic stroke without visible large or medium vessel occlusion (LVO or MVO) within 24 hours of last known well or of onset of stroke symptom progression. However, its efficacy was countered by the higher rate of symptomatic intracranial haemorrhage (sICH).

“Patients without LVO or MVO may suffer from major disability owing to local branch occlusion, artery-to-artery embolism, haemodynamic impairment, and in situ thrombo-occlusion,” said Dr Wenjie Zi from the Xinqiao Hospital of Army Medical University, Chongqing, China, at the Closing Main Event of ISC 2023.

Apart from early antithrombotic therapy, there are no current instituted treatments for these patients, Zi stressed. “Unfortunately, the benefits of conventional therapies such as oral aspirin is far less than reperfusion therapies [such as IVT* or EVT*].”

The team enrolled 1,177 patients with disabling ischaemic stroke without LVO or MVO (median age 68 years, 64 percent male, median NIHSS** score 9) within 24 hours of stroke onset or symptom progression. They were randomized to IV tirofiban plus oral placebo (n=606) or oral aspirin plus IV placebo (n=571). Tirofiban was administered as an initial infusion of 0.4 μg/kg/min for 30 minutes followed by continuous infusion of 0.1 μg/kg/min for up to 48 hours. [ISC 2023, abstract LB24]

Although participants were enrolled within 24 hours of stroke onset (median time from stroke onset or progression to initial treatment 11 hours), more than half were ineligible for reperfusion therapies.

“Tirofiban resulted in a higher overall proportion of excellent outcomes compared with low-dose aspirin at the cost of a higher risk of sICH,” said Zi.

These were reflected by the greater fraction of tirofiban vs placebo recipients who achieved mRS*** 0–1 at day 90 (29.1 percent vs 22.2 percent; adjusted risk ratio, 1.26; p=0.02). Safety-wise, there were six tirofiban recipients who had sICH as opposed to none in the placebo arm (p=0.03).

Rapid onset of action

Tirofiban is a fast-acting, highly selective, low-molecular weight nonpeptide glycoprotein IIb/IIIa receptor inhibitor, with a short half-life that allows bleeding time to revert to normal within 3 hours of administration. Not only does it block platelet aggregation, but it also promotes disaggregation of newly formed platelet aggregates, Zi explained.

Data on tirofiban did not demonstrate benefit for early stroke management. [Stroke 2011;42:2388-2392] But Zi pointed out that previous evaluations included patients with LVO or MVO or cardiogenic embolic stroke who were unlikely to respond to tirofiban and excluded those who failed to respond to IVT but might respond well to tirofiban.

“What if we instead excluded those unlikely to respond and included patients who might respond to therapy? Would tirofiban be effective for these selected patients?,” Zi stressed.

“[As such,] we focused on a broad population of acute ischaemic stroke patients for whom there is no recommended treatment,” said Zi in a press release. “[These were patients who] had an ischaemic stroke within 24 hours but are ineligible for reperfusion therapy, progressive stroke symptoms between 24 and 96 hours after onset, neurologic deterioration after receiving IVT, or had IVT but showed no improvement.”

Promising results but more trials needed

However, the results may not be generalizable to other cohorts as the study was only conducted in China, Zi pointed out. “[T]he epidemiology and aetiology of stroke is different in Chinese patients compared with other populations … [Asians have a] higher rate of intracranial artery stenosis.”

“[While] the results are promising … we have an urgent need to explore tirofiban further for stroke treatment,” Zi said.