J Stroke.  2021 Jan;23(1):91-102. 10.5853/jos.2020.01788.

Safety and Angiographic Efficacy of Intra-Arterial Fibrinolytics as Adjunct to Mechanical Thrombectomy: Results from the INFINITY Registry

• Kaesmacher J
• Abdullayev N
• Maamari B
• Dobrocky T
• Vynckier J
• Piechowiak EI
• Pop R
• Behme D
• Sporns PB
• Styczen H
• Virtanen P
• Meyer L
• Meinel TR
• Cantré D
• Kabbasch C
• Maus V
• Pekkola J
• Fischer S
• Hasiu A
• Schwarz A
• Wildgruber M
• Seiffge DJ
• Langner S
• Martinez-Majander N
• Radbruch A
• Schlamann M
• Mihoc D
• Beaujeux R
• Strbian D
• Fiehler J
• Mordasini P
• Gralla J
• Fischer U

• KMID: 2512358
• DOI: http://doi.org/10.5853/jos.2020.01788

Abstract

Background and Purpose
Data on safety and efficacy of intra-arterial (IA) fibrinolytics as adjunct to mechanical thrombectomy (MT) are sparse.
Methods
INtra-arterial FIbriNolytics In ThrombectomY (INFINITY) is a retrospective multi-center observational registry of consecutive patients with anterior circulation large-vessel occlusion ischemic stroke treated with MT and adjunctive administration of IA fibrinolytics (alteplase [tissue plasminogen activator, tPA] or urokinase [UK]) at 10 European centers. Primary outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the European Cooperative Acute Stroke Study II definition. Secondary outcomes were mortality and modified Rankin Scale (mRS) scores at 3 months.
Results
Of 5,612 patients screened, 311 (median age, 74 years; 44.1% female) received additional IA after or during MT (194 MT+IA tPA, 117 MT+IA UK). IA fibrinolytics were mostly administered for rescue of thrombolysis in cerebral infarction (TICI) 0-2b after MT (80.4%, 250/311). sICH occurred in 27 of 308 patients (8.8%), with an increased risk in patients with initial TICI0/1 (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1 to 5.0 per TICI grade decrease) or in those with intracranial internal carotid artery occlusions (aOR, 3.7; 95% CI, 1.2 to 12.5). In patients with attempted rescue of TICI0-2b and available angiographic follow-up, 116 of 228 patients (50.9%) showed any angiographic reperfusion improvement after IA fibrinolytics, which was associated with mRS ≤2 (aOR, 3.1; 95% CI, 1.4 to 6.9).
Conclusions
Administration of IA fibrinolytics as adjunct to MT is performed rarely, but can improve reperfusion, which is associated with better outcomes. Despite a selection bias, an increased risk of sICH seems possible, which underlines the importance of careful patient selection.

Keyword

Tissue plasminogen activator; Stroke; Thrombolytic therapy; Thrombectomy; Intracranial hemorrhages

Figure

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  Figure 1. Risk of symptomatic intracranial hemorrhage (sICH) according to thrombolysis in cerebral infarction (TICI). Data on sICH was available in 308/311 patients. SICH occurred in 5/33 patients (15.2%) with TICI0/1, in 8/66 patients (12.1%) with TICI2a, in 14/187 patients (7.5%) with TICI2b and did not occur in 22 patients with TICI3. There was a decreased risk of sICH with higher TICI grade (adjusted odds ratio [aOR] per grade increase derived from logistic regression analysis: aOR, 0.43; 95% confidence interval, 0.20 to 0.94). TICI scores used were before administration of intra-arterial fibrinolytics in cases of rescue of TICI0-2b reperfusions. In other cases (treatment of emboli in new territory or administration during first retrievals at the operator’s discretion) final TICI scores were used.

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  Figure 2. Thrombolysis in cerebral infarction (TICI) grade change after intra-arterial (IA) fibrinolytics. (A) After IA fibrinolytics, TICI shifted towards better scores (TICI grade improvement noted in 28.9% of patients). (B) Most patients with TICI2b did not improve to TICI3; however, any angiographic reperfusion improvement was relatively common in patients with initial TICI2b reperfusions (46.1%, 70/152).

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  Figure 3. Three-month functional outcome of patients treated with mechanical thrombectomy (MT) and intra-arterial (IA) fibrinolytics. (A) Three-month functional outcome was available for 300/311 patients treated with MT+IA fibrinolytics. Functional independence (modified Rankin Scale [mRS] ≤2) was observed in 37.0% (111/300) of patients and 16.7% (50/300) of patients had died. (B, C) Functional outcomes were better in patients receiving IA urokinase (UK) (odds ratio for mRS ≤2, 2.22; 95% confidence interval [CI], 1.37 to 3.60). However, this association was not statistical significant after adjustment for clinical confounders and baseline group imbalances (IA UK vs. IA tissue plasminogen activator [tPA]: adjusted odds ratio, 1.35; 95% CI, 0.87 to 2.09).

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  Figure 4. Three-month functional outcome with strata of angiographic reperfusion improvement after administering intra-arterial (IA) fibrinolytics. For 228/250 patients with an intention to improve TICI 0-2b, angiographic control runs after administration of IA fibrinolytics were available. Three-month functional outcome was available in 221 of these 228 patients. (A) Any angiographic improvement was observed in 110/221 and was associated with modified Rankin Scale (mRS) ≤2 after adjusting for covariates outlined in the methods section (adjusted odds ratio, 3.11; 95% confidence interval, 1.41 to 6.86). (B) The 111/221 patients showed no angiographic improvement. TICI, thrombolysis in cerebral infarction.

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