RESCUE BT: IV Tirofiban No Help During Stroke Thrombectomy
Any hint of benefit in patients with large-artery atherosclerosis is hypothesis-generating only, Joseph Broderick says.
Administering IV tirofiban before endovascular thrombectomy does not improve functional outcomes in patients with acute ischemic strokes caused by a large-vessel occlusions (LVOs), the randomized RESCUE BT trial shows.
At 90 days, the median modified Rankin Scale score (mRS) was 3 in both the tirofiban and placebo groups, with significant difference in the overall distribution of disability scores (adjusted common OR 1.08; 95% CI 0.86-1.36), researchers led by Zhongming Qiu, MD (Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University, Chongqing, China), report. As-treated and per-protocol analyses yielded similar results.
The findings, published in the August 9, 2022, issue of JAMA, “do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke.”
Joseph Broderick, MD (UC Gardner Neuroscience Institute, Cincinnati, OH), who was not involved in the study, agreed. He added, however, that the potential use of adjunctive antithrombotic therapies during thrombectomy remains a ripe area for research.
“The best use and which populations benefit the most is still an open question,” he said. “I think it’s still a fruitful ground for additional treatments, but it also points that maybe we should talk about standardizing or minimizing some of the things like heparin based upon the MR CLEAN-MED study that was reported earlier.”
The RESCUE BT Trial
Although endovascular thrombectomy has been shown to improve functional outcomes in patients with LVO strokes in multiple trials, the procedure fails to provide adequate reperfusion in many patients. “Unsuccessful reperfusion likely arises in part from mechanical thrombectomy devices causing traumatic damage to the vascular endothelium with subendothelial matrix exposure, leading to platelet activation, adhesion, and aggregation and potentially resulting in reocclusion and thromboembolic complications,” Qiu et al write.
Therefore, it’s possible that administering antiplatelet therapy could have a benefit. Tirofiban, a glycoprotein IIb/IIIa inhibitor used in the management of ACS, has been evaluated in the setting of acute ischemic stroke across multiple studies, which have provided conflicting results. Until now, it’s potential utility in acute stroke had not been evaluated in a randomized trial.
RESCUE BT, performed across 55 hospitals in China, included 948 patients (mean age 67 years; 41.2% women) who presented with an LVO stroke within 24 hours of when they were last known to be well. Investigators randomized them to either IV tirofiban or placebo given before endovascular thrombectomy. Tirofiban was administered as a bolus dose of 10 µg/kg followed by a continuous infusion of 0.15 µg/kg/min for up to 24 hours. IV heparin was allowed during thrombectomy and subcutaneous heparin or low-molecular-weight heparin could be used for prophylaxis of deep vein thrombosis after the procedure.
The primary outcome was the disability level at 90 days according to the overall distribution of mRS scores, and there was no difference observed between trial arms. All secondary clinical efficacy outcomes, and most of the technical efficacy outcomes, occurred at similar rates in the two groups, although the proportion of patients receiving a rescue drug was lower in the tirofiban arm (8.4% vs 12.0%; P = 0.04).
As for safety, symptomatic intracranial hemorrhage within 48 hours was seen in 9.7% of tirofiban-treated patients and 6.4% of those who received placebo, a nonsignificant difference (P = 0.07). There was a higher rate of any radiologic intracranial hemorrhage in the tirofiban group (34.9% vs 28.0%; P = 0.02).
Mortality at 90 days was not significantly different between the tirofiban and placebo arms (18.1% vs 16.9%; P = 0.63).
Hint of Benefit in Subgroup
There were no significant interactions seen among various subgroups when it came to the primary endpoint, although there was a hint of benefit with tirofiban when the stroke etiology was large-artery atherosclerosis (seen in about 46% of patients).
“Observational studies have suggested that intravenous tirofiban was associated with substantial reperfusion rates and favorable functional outcomes among patients with large-artery atherosclerosis strokes,” the investigators note. “Particularly in Asian populations, large-artery atherosclerosis stroke is often due to intracranial, rather than extracranial, atherosclerosis so that the target occlusion is comprised of both in situ atherosclerotic plaque and supervening thrombus.”
Thrombectomy will remove the clot, but the disrupted atherosclerotic lesion—which often requires rescue angioplasty with or without stenting—may increase the likelihood of platelet activation and rethrombosis that could be responsive to tirofiban, Qiu et al speculate. “The current study’s hypothesis-generating finding of potential benefit of tirofiban in patients with ischemic stroke due to large-artery atherosclerosis may merit a future confirmatory trial confined to this population.”
Indeed, Broderick said, the subgroup findings can only be used to lay the groundwork for future studies. “These questions should only be asked right now in the setting of a randomized trial,” he emphasized.
In an accompanying editorial, Craig Anderson, MD, PhD (The George Institute for Global Health, UNSW Sydney, Australia), and colleagues say that “any potential modest benefit of tirofiban in the large-artery atherosclerosis subgroup was counterbalanced by the overall risk of serious bleeding as the single major complication of thrombectomy.”
They point out, too, that the MR CLEAN-MED trial, which evaluated different antithrombotic regimens that included aspirin, unfractionated heparin, or both during thrombectomy, showed an increased risk of symptomatic intracranial hemorrhage without any clinical benefit.
“Thus, any further investigation of targeted approaches with tirofiban, or other potent antiplatelet agent(s), in intracranial atherosclerosis would benefit from a better understanding of the interactions between atherosclerosis and thrombosis, the importance of thrombus composition (‘harder’ fibrin-rich and red blood cell-rich thrombi versus ‘softer’ platelet-rich thrombi), and the relation of blood flow to vascular occlusion in the progression of large-vessel occlusion in acute ischemic stroke.”
RESCUE BT Trial Investigators. Effect of intravenous tirofiban vs placebo before endovascular thrombectomy on functional outcomes in large vessel occlusion stroke: the RESCUE BT randomized clinical trial. JAMA. 2022;328(6):543-553.
Anderson CS, Song L, Liu J. Therapeutic strategies for intracranial atherosclerosis. JAMA. 2022;328(6):529-531.
- The trial was supported by Lunan Pharmaceutical Group, the National Natural Science Foundation of China, and the Army Medical University Clinical Medical Research Talent Training Program.
- Anderson and Qiu report no relevant conflicts of interest.