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Original Investigation
December 9, 2019

Safety and Efficacy of Intra-arterial Urokinase After Failed, Unsuccessful, or Incomplete Mechanical Thrombectomy in Anterior Circulation Large-Vessel Occlusion Stroke

Author Affiliations
  • 1University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland
  • 2University Institute of Diagnostic, Interventional and Pediatric Radiology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland
  • 3Department of Neurology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland
JAMA Neurol. Published online December 9, 2019. doi:10.1001/jamaneurol.2019.4192
Key Points

Questions  Is adjunctive administration of intra-arterial urokinase safe after failed or incomplete mechanical thrombectomy?

Findings  In this cohort study of 993 consecutive patients treated with mechanical thrombectomy, additional administration of intra-arterial urokinase (performed in 100 patients) was not associated with an increased risk of symptomatic intracranial hemorrhage (5.2% vs 6.9%) and was associated with higher rates of 90-day functional independence in fully adjusted models.

Meaning  In selected patients with incomplete or failed mechanical thrombectomy, adjunctive treatment with intra-arterial urokinase was safe, and further evaluation of this treatment approach seems warranted.

Abstract

Importance  Achieving complete reperfusion is a key determinant of good outcome in patients treated with mechanical thrombectomy (MT). However, data on treatments geared toward improving reperfusion after incomplete MT are sparse.

Objective  To determine whether administration of intra-arterial urokinase is safe and improves reperfusion after failed or incomplete MT.

Design, Setting, and Participants  This observational cohort study included a consecutive sample of patients treated with second-generation MT from January 1, 2010, through August 4, 2017. Data were collected from the prospective registry of a tertiary care stroke center. Of 1274 patients screened, 69 refused to participate, and 993 met the observational studies inclusion criteria of a large vessel occlusion in the anterior circulation. Data were analyzed from September 1, 2017, through September 20, 2019.

Intervention  One hundred patients received intra-arterial urokinase after failed or incomplete MT using manual microcatheter injections.

Main Outcomes and Measures  Primary safety outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the Prolyse in Acute Cerebral Thromboembolism II criteria. Secondary end points 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.

Results  After exclusion of patients with posterior circulation strokes and those treated with intra-arterial thrombolytics only, 993 patients were included in the final analyses (median age, 74.6 [interquartile range, 62.6-82.2] years; 505 [50.9%] women). 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 (53 [53.0%]). After adjusting for baseline characteristics underlying case selection, intra-arterial urokinase was not associated with an increased risk of sICH (adjusted odds ratio [aOR], 0.81; 95% CI, 0.31-2.13) or 90-day mortality (aOR, 0.78; 95% CI, 0.43-1.40). Among 53 cases of partial or near-complete reperfusion and treated with intra-arterial urokinase, 32 (60.4%) had early reperfusion improvement, and 18 of 53 (34.0%) had an improvement in TICI grade. Correspondingly, 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 (aOR, 1.93; 95% CI, 1.11-3.37).

Conclusions and Relevance  In selected patients, adjunctive treatment with intra-arterial urokinase during or after MT was safe and improved angiographic reperfusion. Systemic evaluation of this approach in a multicenter prospective registry or a randomized clinical trial seems warranted.

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