Elena Zapata-Arriaza, MD

Yang J, Wu Y, Gao X, Bivard A, Levi CR, Parsons MW, Lin L. Intraarterial Versus Intravenous Tirofiban as an Adjunct to Endovascular Thrombectomy for Acute Ischemic Stroke. Stroke. 2020;51:2925–2933.

Intracranial large vessel re-occlusion can happen during endovascular treatment (EVT) of acute ischemic stroke (AIS), either by endothelial damage triggered by the thrombectomy device itself or by the presence of intracranial atherosclerosis. Intra- or periprocedural antiplatelet therapy with tirofiban could be a solution that needs growing scientific evidence to back it up. Based on their own previous studies, Yang et al. aimed to evaluate the treatment effect of intraarterial (IA) vs intravenous (iv) tirofiban during EVT in AIS.

Authors from Chinese centers performed a retrospective study from 2017-19 of patients with acute ischemic stroke with large vessel occlusion who received endovascular thrombectomy within 24 hours of stroke onset. Before EVT, the thrombolysis treatment of intravenous tPA was administered to eligible patients. After EVT, antiplatelet treatment with 100 mg aspirin or 75 mg clopidogrel was administered within 24 hours if no intracranial hemorrhage was shown on follow-up noncontrast computed tomography and intravenous tPA was not used before the procedure. If intravenous tPA was used before the EVT procedure, antiplatelet treatment was initiated after 24 hours. Patient selection for tirofiban treatment was at the discretion of the interventionalists. For either IA or IV tirofiban, the routine practice was injection of a bolus dose of 10 µg/kg, followed by an intravenous infusion of tirofiban at a rate of 0.15 µg/(kg·min) for 12 to 24 hours. Patients were divided into 3 groups: no tirofiban, intraarterial tirofiban, and intravenous tirofiban. The 3 groups were compared in terms of recanalization rate, symptomatic intracerebral hemorrhage, in-hospital death rate, 3-month death, and 3-month outcomes measured by modified Rankin Scale score (good clinical outcome of 0–2, poor outcome of 5–6).

Final results demonstrated that compared with the no-tirofiban group, the intravenous tirofiban group showed significantly increased recanalization, an increased rate of 3-month good outcome, and a lower rate of 3-month poor outcome. Interestingly, in the intravenous tirofiban group, patients

had a higher rate of good collateral and higher rate of small core volume than patients in the no-tirofiban group. There was no significant difference between the tirofiban intravenous and no-tirofiban groups in terms of symptomatic intracerebral hemorrhage. However, symptomatic intracerebral hemorrhage was significantly increased in the intraarterial-tirofiban group compared with the no-tirofiban group, with an increased rate of in-hospital death and increased rate of 3-month death. The intraarterial-tirofiban and no-tirofiban groups showed no significant difference in recanalization rate.

This study highlights that the use of tirofiban in the context of EVT of AIS can be safe and effective even when associated with the use of IV fibrinolysis, and that the most reliable route of administration is intravenous. In patients who undergo mechanical thrombectomy, the oral route is limited, and having an IV or AI antiplatelet treatment that is safe and effective opens an interesting route for those cases of early intracranial reocclusion, shortening and simplifying the procedures. If the risk of reocclusion in a routine endovascular treatment of an intracranial stenosis is considerable, in an acute setting, without previous double antiplatelet therapy, and with time against us, the risks skyrocket, decisions become complicated and the patient loses out. For this reason, having evidence in the use of a fast-acting antiplatelet that shows promising results of safety and efficacy gives us a useful tool that can be studied in a prospective clinical trial.

However, we must not forget some limitations. The study uses the same doses for IA and IV routes, which does not seem logical given the speed of contact of the different routes of the drug with the thrombus. It is possible that the IA route at lower doses may be safer and effective, similar to the IV route, and its action is more direct. Likewise, it should be noted that the intravenous route is used earlier, which is to be expected when an atheromatous origin of intracranial occlusion is suspected. Also, the patients in this group have lower infarct cores so the groups may not be comparable in regards to stroke severity. Finally, given that the study is carried out in an Asian population with high rates of intracranial stenosis, these results must be taken with caution for generalization.

The study is a starting point to build relevant evidence on the use of antiplatelet drugs that may work synergistically with our current recanalization therapies in patients with large vessel occlusive disease such as intracranial atherosclerosis. Studying this in a prospective trial may be helpful in determining its role as a treatment option for re-occlusion prevention.