Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Dec;13(12):1073-1080.
doi: 10.1136/neurintsurg-2020-016680. Epub 2021 Jan 29.

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: a systematic review and meta-analysis of observational data

Johannes Kaesmacher  1   2 , Thomas Raphael Meinel  3 , Christoph Kurmann  4 , Osama O Zaidat  5 , Alicia C Castonguay  6 , Syed F Zaidi  6 , Nils Mueller-Kronast  7 , Manon Kappelhof  8 , Diederik W J Dippel  9 , Marc Soudant  10 , Serge Bracard  11 , Michael D Hill  12 , Mayank Goyal  13 , Daniel Strbian  14 , Daniel M Heiferman  15 , William Ashley  16 , Mohammad Anadani  17   18 , Alejandro M Spiotta  18 , Tomas Dobrocky  4 , Eike I Piechowiak  4 , Marcel Arnold  3 , Martina Goeldlin  3 , David Seiffge  3 , Pascal J Mosimann  4   19 , Pasquale Mordasini  4 , Jan Gralla  4 , Urs Fischer  3
Affiliations
Meta-Analysis

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: a systematic review and meta-analysis of observational data

Johannes Kaesmacher et al. J Neurointerv Surg. 2021 Dec.

Abstract

Background: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse.

Methods: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days).

Results: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics.

Conclusion: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty.

Keywords: stroke; thrombectomy; thrombolysis.

PubMed Disclaimer

Conflict of interest statement

Competing interests: Related: UF and JG are global PIs for the SWIFT DIRECT study (Solitaire With the Intention for Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire Stent-Retriever Thrombectomy in Acute Anterior Circulation Stroke) supported by Medtronic. Unrelated: JG is a global PI of STAR (Solitaire FR Thrombectomy for Acute Revascularisation Observational study), Clinical Event Committee member of the PROMISE study (European Registry on the ACE Reperfusion Catheters and the Penumbra System in the Treatment of Acute Ischemic Stroke; Penumbra), Consultancy, and receives Swiss National Science Foundation (SNSF) grants for MRI in stroke. UF receives research grants from SNSF and serves as a consultant for Medtronic and Stryker. MA received speaker honoraria from Bayer, Boehringer Ingelheim, and Covidien; advisory board honoraria from Amgen Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Covidien, Daichy Sankyo and Nestlé Health Science; research grant provided by the Swiss Heart Foundation. JK reports grants from SAMW / Bangerter Foundation, the Swiss Stroke Society and non-financial support from Stryker and Pfizer outside the submitted work. DWJD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from AngioCare BV, Covidien/EV3®, MEDAC Gmbh/LAMEPRO, Penumbra Inc., Top Medical/Concentric, Stryker, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC and Cerenovus for research, all paid to institution. MG reports licensing agreement for systems of acute stroke diagnosis for GE Healthcare and Consultancy for Medtronic, Stryker, MicroVention and Mentice as well as unrestricted research grant by Stryker for the UNMASK-EVT study. MDH has a patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients pending to US patent office number 62/086077 and owns stock in Calgary Scientific, Inc—a company that focuses on medical imaging software.

Figures

Figure 1
Figure 1
Forest plot of summary odds ratios for sICH in patients with and without adjunctive administration of IAF during MT. *For Anadani et al we used PH2 as sICH surrogate. IAF, intra-arterial fibrinolytics; MT, mechanical thrombectomy; PH2, parenchymal hematoma type 2; sICH, symptomatic intracranial hemorrhage; tPA, tissue plasminogen activator; uPA, urokinase.
Figure 2
Figure 2
Forest plot of summary odds ratios for sICH in patients with and without adjunctive administration of IAF during MT with strata of IVT before MT. (A) With intravenous tPA (IVT) before MT. (B) Without IVT MT. *For Anadani et al we used PH2 as sICH surrogate. IAF, intra-arterial fibrinolytics; IVT, intravenous thrombolysis; MT, mechanical thrombectomy; PH2, parenchymal hematoma type 2; sICH, symptomatic intracranial hemorrhage; tPA, tissue plasminogen activator; uPA, urokinase.
Figure 3
Figure 3
Forest plot of summary odds ratios for sICH comparing patients with bridging therapy, MT and added IAF to patients with direct MT and added IAF. *For Anadani et al we used PH2 as sICH surrogate. IAF, intra-arterial fibrinolytics; IVT, intravenous thrombolysis; MT, mechanical thrombectomy; PH2, parenchymal hematoma type 2; sICH, symptomatic intracranial hemorrhage; tPA, tissue plasminogen activator; uPA, urokinase.
Figure 4
Figure 4
Forest plot of unadjusted odds ratios for mortality at 3 months in patients with and without adjunctive administration of IAF during MT. *For Anadani et al we used PH2 as sICH surrogate. IAF, intra-arterial fibrinolytics; MT, mechanical thrombectomy; PH2, parenchymal hematoma type 2; sICH, symptomatic intracranial hemorrhage; tPA, tissue plasminogen activator; uPA, urokinase.
See this image and copyright information in PMC

References

    1. Liebeskind DS, Bracard S, Guillemin F, et al. . eTICI reperfusion: defining success in endovascular stroke therapy. J Neurointerv Surg 2019;11:433–8. 10.1136/neurintsurg-2018-014127 - DOI - PubMed
    1. Rizvi A, Seyedsaadat SM, Murad MH, et al. . Redefining 'success': a systematic review and meta-analysis comparing outcomes between incomplete and complete revascularization. J Neurointerv Surg 2019;11:9–13. 10.1136/neurintsurg-2018-013950 - DOI - PubMed
    1. Kaesmacher J, Dobrocky T, Heldner MR, et al. . Systematic review and meta-analysis on outcome differences among patients with TICI2b versus TICI3 reperfusions: success revisited. J Neurol Neurosurg Psychiatry 2018;89:910–7. 10.1136/jnnp-2017-317602 - DOI - PMC - PubMed
    1. Zaidat OO, Castonguay AC, Linfante I, et al. . First pass effect: a new measure for stroke thrombectomy devices. Stroke 2018;49:660–6. 10.1161/STROKEAHA.117.020315 - DOI - PubMed
    1. Nikoubashman O, Dekeyzer S, Riabikin A, et al. . True first-pass effect. Stroke 2019;50:2140–6. 10.1161/STROKEAHA.119.025148 - DOI - PubMed

MeSH terms

Substances