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

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 PARTICIPANTSThis 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 MEASURESPrimary 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 Յ2). Efficacy was evaluated angiographically, applying the Thrombolysis in Cerebral Infarction (TICI) scale. RESULTSAfter 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 RELEVANCEIn 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.

Endovascular therapy in patients with large vessel occlusion due to cardioembolism versus large-artery atherosclerosis

“… 1 Our institutional protocol included intra-arterial thrombolysis with urokinase (Medac GmbH and Opopharma Vertriebs AG), injected manually before or next to and distal to the thrombus, in dosages of up to 1,000,000 IU, in lower dosages in the case of pre-interventional intravenous thrombolysis. 17 Our institutional protocol did not include tenecteplase for intravenous thrombolysis.…”

Intracranial Bleeding After Reperfusion Therapy in Acute Ischemic Stroke

“…In the case of MT failure, the surgeon may use an adjuvant therapy that has not been tested for this indication by a RCT. A few of these therapies have been reported in small series: intra-arterial tPA ( 132 ), intra-arterial Urokinase ( 133 ), and intravenous Tirofiban ( 134 , 135 ). These series did not show significant association between these adjunctive therapies and sICH.…”

Threshold-based Identification of Persistent Infarction after Successful Endovascular Treatment: Re-evaluating the “Core”

“…Intra-venous thrombolysis with recombinant tissue plasminogen activator (rTPA) was administered ahead of intervention in 45 cases (N=45/90, 50%). Intra-arterial thrombolysis with urokinase 14 as stand-alone therapy was used in four cases (N=4/90, 4.4%). Intervention was waived in eight cases (N=8/90, 8.9%) due to preinterventional reperfusion on DSA ahead of endovascular treatment.…”