Elena Zapata-Arriaza, MD

Kaesmacher J, Bellwald S, Dobrocky T, Meinel TR, Piechowiak EI, Goeldlin M, et al. Safety and Efficacy of Intra-arterial Urokinase After Failed, Unsuccessful, or Incomplete Mechanical Thrombectomy in Anterior Circulation Large-Vessel Occlusion Stroke. JAMA Neurol. 2020;77:318–326.

Given the association among successful reperfusion and good functional outcomes, it is rational to look for tools that allow us to achieve the best TICI in patients undergoing mechanical thrombectomy. Within the ways to improve recanalization, we find the employment of safe and reliable devices with the ability to navigate more and more distally or the use of intra-arterial medication at the occlusion site. To determine the safety and efficacy of intra-arterial urokinase after failed or incomplete reperfusion in stroke mechanical thrombectomy(MT), Kaesmacher et al. performed an observational cohort study, with data collected from a prospective registry in a tertiary care stroke center from 2010-2017.

Primary safety outcome was the occurrence of symptomatic intracranial hemorrhage (sICH), and secondary endpoints included 90-day mortality and 90-day functional independence (defined as modified Rankin Scale score of 2). Efficacy was evaluated angiographically, applying the Thrombolysis in Cerebral Infarction (TICI) scale. Patients who were treated with intra-arterial urokinase (with or without intravenous tPA) only and patients presenting with posterior circulation large-vessel occlusion or distal anterior circulation vessel occlusions were excluded. Endovascular treatment was performed with second generation devices only, mostly stent retrievers. Urokinase was injected manually before or next to and distal to the thrombus, usually via the same microcatheter used to introduce the MT device. Final TICI grades were assessed by an independent researcher. When intra-arterial urokinase was administered after failed or incomplete MT, TICI grade was assessed before and after the intra-arterial urokinase administration. If no change occurred in TICI after urokinase administration, the rater had to assess whether any kind of angiographic improvement occurred compared with before administration of intra-arterial urokinase.

Among 993 final included patients, additional intra-arterial urokinase was administered in 100 patients (10.1%). The most common reason for administering intra-arterial urokinase was incomplete reperfusion (TICI<3) after MT. Given the main results, this study found that intra-arterial urokinase was not associated with an increased risk of sICH or 90-day mortality. Among cases of partial or near-complete reperfusion, intra-arterial urokinase treatment helped to early reperfusion improvement, and to the TICI grade amelioration. Finally, although there was no difference when adjusting for baseline characteristics, patients treated with intra-arterial urokinase had higher rates of functional independence after adjusting for the selection bias favoring a priori poor TICI grades in the intra-arterial urokinase group.

Despite being an observational, non-randomized study, the results reported in this article provide a basis on which to support future studies that validate the findings presented. An interesting conclusion is the possibility of using urokinase in cases with incomplete reperfusion. This finding gives us a useful tool for those cases in which we have an occlusion of a distal branch of an eloquent area, on which trying a mechanical thrombectomy pass associates a high risk of complications. However, the study’s own design and limitations make validation of its results in randomized studies indispensable. The advance in the development of devices for MT has allowed us to perform treatments in more distal occlusions, safely and effectively. Therefore, comparing the usefulness of urokinase or any other intra-arterial medication with these devices could guide us on the best guideline to follow in patients with incomplete recanalization.