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Urokinase Safely Improves Angiographic Reperfusion in Stroke

Intra-arterial urokinase improved Thrombolysis in Cerebral Infarction (TICI) scale scores and independence at 90 days, without increasing the risk of symptomatic intracranial hemorrhage.

Johannes Kaesmacher, MD

New data suggests that selective patients with stroke who are treated with mechanical thrombectomy can benefit safely from intra-arterial urokinase, with improved angiographic reperfusion.

The study, conducted by Johannes Kaesmacher, MD, University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, and colleagues, observed that intra-arterial urokinase improved Thrombolysis in Cerebral Infarction (TICI) scale scores and independence at 90 days, without increasing the risk of symptomatic intracranial hemorrhage.

“Achieving complete reperfusion is a key determinant of good outcomes in patients treated with mechanical thrombectomy. However, data on treatments geared toward improving reperfusion after incomplete mechanical thrombectomy are sparse,” Kasemacher and colleagues wrote.

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In the cohort of 993 patients with failed or incomplete mechanical thrombectomy, 10.1% (n = 100) required additional intra-arterial urokinase. The most common reasons for its administration were an incomplete reperfusion (TICI score <3), which occurred in 53% (n = 53) of patients, facilitation of clot removal in 25% (n = 25), rescue after failed thrombectomy in 15% (n = 15), and for the treatment of emboli to new territory in 7.0% (n = 7).

Asymptomatic bleeding was less frequent in patients receiving intra-arterial urokinase (16.3% [15 of 92] compared to 27.2% [222 of 818]; P&thinsp;=&thinsp;.02), and mortality at day 90 tended to be lower (19.2% [19 of 99] compared to 27.3% [235 of 860]; P&thinsp;=&thinsp;.09). After adjustments for baseline differences, the use of intra-arterial urokinase also was not associated with an increased risk of symptomatic intracranial hemorrhage (5.2% vs. 6.9%; adjusted odds ratio [OR], 0.81; 95% CI, 0.31—2.13) nor 90-day mortality (adjusted OR, 0.78; 95% CI, 0.43–1.40).

Of the 53 patients with incomplete reperfusion, 60.4% (n = 32) experienced early reperfusion improvements, relevant to the TICI grade in 34% of cases (n = 18): 10 improved from TICI 2a to TICI 2b, and 8 cases improved from TICI 2a or 2b to TICI 3.

Additionally, after adjusting for technical end points such as selection bias favoring poor TICI grades in the intra-arterial urokinase group, the treatment addition was found to be associated with functional independence (adjusted OR, 1.93; 95% CI, 1.11-3.37) at day 90.

“Although the nonrandomized nature of these observational data does not allow for treatment recommendations, the observed angiographic and clinical benefits stress the need for further evaluation of this approach in a multicenter prospective registry or a randomized clinical trial,” Kasemacher and colleagues wrote.

An accompanying editorial from Victor Lopez-Rivera, MD, and Sunil A. Sheth, MD, noted that this work “move[s] the field 1 step closer to achieving the goal of complete revascularization,” and that despite some needs remaining to perfect this technique, these data “provide evidence on behalf of one such approach, one that satisfyingly builds on the original progenitor technique of endovascular stroke therapy.”2


1. Kaesmacher J, Bellwald S, Dobrocky T, 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. Published online December 9, 2019. doi: 10.1001/jamaneurol.2019.4192.

2. Lopez-Rivera V, Sheth SA. Potential of Intra-arterial Urokinase After Incomplete Mechanical Thrombectomy: Looking Back, Moving Forward. JAMA Neurol. Published online December 9, 2019. doi: 10.1001/jamaneurol.2019.3984.