DALLAS — Adding tirofiban (Aggrastat) to aspirin for dual antiplatelet therapy (DAPT) within 24 hours of acute ischemic stroke improved outcomes for patients who weren’t candidates for thrombolytic or endovascular treatment, according to a phase III trial from China.
The combination of the glycoprotein IIb/IIIa inhibitor with aspirin shifted modified Rankin Scale (mRS) scores in a favorable direction compared with aspirin plus placebo, reported Wenjie Zi, MD, of Xinqiao Hospital and the Second Affiliated Hospital, Army Medical University (Third Military Medial University) in Chongqing, China.
The proportion with an excellent functional outcome, marked by an mRS of 0-1, was 29.1% with tirofiban plus aspirin versus 22.2% with aspirin and placebo (adjusted RR 1.26, 95% 1.04-1.53, P=0.02).
Early DAPT did increase symptomatic intracranial hemorrhage but the rate was low at less than 1%, with six cases versus none out of the trial’s 1,177 randomized patients (P=0.03), Zi said in a presentation at the American Stroke Association International Stroke Conference (ISC).
“The benefits outweigh the risks,” summarized ISC chair and session moderator Tudor Jovin, MD, of Cooper Neurological Institute in Camden, New Jersey.
“But to be honest, I’m not that surprised,” he told MedPage Today, noting that DAPT has already proven to benefit patients with minor stroke or transient ischemic attack — a group not typically treated with thrombectomy or thrombolytics — in studies in which most patients did not have large vessel occlusion, when used as preventive therapy.
“So this trial brings this more potent antiplatelet therapy regimen a bit earlier, around the time of the stroke,” he added. “It is very promising. We’re making some progress also in treatment of patients who don’t have large vessel occlusion or medium vessel occlusion.”
Two prior trials had failed to show a benefit of tirofiban in the early management of stroke (SETIS and SaTIS), Zi noted. However, those had included large-to-medium vessel occlusion strokes and cardiogenic embolic stroke, while excluding patients with contraindications to IV thrombolysis.
The current RESCUE BT2 trial included 1,177 adults with acute ischemic stroke without large- or medium-size vessel occlusion who were enrolled within 24 hours of stroke onset or stroke symptom progression at 117 centers in China from Oct. 20, 2020 to June 30, 2022.
They were randomly assigned to double-blind treatment with oral low-dose aspirin plus a placebo IV or placebo pills plus tirofiban, given as an initial infusion of 0.4 μg/kg/min for 30 minutes then continuous infusion of 0.1 μg/kg/min for up to 48 hours.
Patients ineligible for IV thrombolytics or endovascular therapy, although within 24 hours of time last known well, represented about 55% of those enrolled. Another one-third of the group was enrolled between 24 and 96 hours after time last known well but within 24 hours of progression by ≥2 points on the NIH Stroke Scale (NIHSS).
Neurological deterioration by ≥4 points on the NIHSS within the first 24 hours after IV thrombolysis was the enrollment criterion for about 7%, while about 5% were enrolled based on no neurological improvement after IV thrombolysis.
The median age of participants was 68. Men comprised about two-thirds of the study population. NIHSS score came in at a median of 9, while median time from stroke onset or progression was 11 hours. Participants with intracranial hemorrhage at baseline were excluded. The six tirofiban-group patients with symptomatic intracranial hemorrhage after treatment were the only ones in the trial with any intracranial hemorrhage on imaging.
Study limitations included the heterogeneity of the patient presentations along with the Asian population studied, with a higher rate of intracranial artery stenosis than might be seen in Western populations. Zi suggested that was a reason for caution in generalizing the results to other populations.
“I do think that there are some particularities in the Chinese population — a lot of their population has intracranial atherosclerotic disease as opposed to embolic strokes or lacunar strokes or small vessel strokes in the Caucasian population — so that should be confirmed in a Caucasian population as well,” Jovin agreed.
He also suggested that a comparator arm of early DAPT with clopidogrel plus aspirin would have been useful, although not all patients can tolerate oral medication within 24 hours after stroke.
The study was funded by Lunan Pharmaceutical Group and the National Natural Science Foundation of China Major Program.
Zi and Jovin disclosed no relationships with industry.
International Stroke Conference
Source Reference: Zi W, et al “Tirofiban for disabling stroke without large or medium size vessel occlusion” ISC 2023; LB24.