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

Johannes Kaesmacher; Thomas Raphael Meinel; Christoph Kurmann; Osama O. Zaidat; Alicia C. Castonguay; Syed F. Zaidi; Nils Mueller-Kronast; Manon Kappelhof; DIederik W.J. DIppel; Marc Soudant; Serge Bracard; Michael D. Hill; Mayank Goyal; Daniel Strbian; Daniel M. Heiferman; William Ashley; Mohammad Anadani; Alejandro M. Spiotta; Tomas Dobrocky; Eike I. Piechowiak; Marcel Arnold; Martina Goeldlin; David Seiffge; Pascal J. Mosimann; Pasquale Mordasini; Jan Gralla; Urs Fischer

doi:10.1136/neurintsurg-2020-016680

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

Johannes Kaesmacher^*, Thomas Raphael Meinel, Christoph Kurmann, Osama O. Zaidat, Alicia C. Castonguay, Syed F. Zaidi, Nils Mueller-Kronast, Manon Kappelhof, DIederik W.J. DIppel, Marc Soudant, Serge Bracard, Michael D. Hill, Mayank Goyal, Daniel Strbian, Daniel M. Heiferman, William Ashley, Mohammad Anadani, Alejandro M. Spiotta, Tomas Dobrocky, Eike I. PiechowiakMarcel Arnold, Martina Goeldlin, David Seiffge, Pascal J. Mosimann, Pasquale Mordasini, Jan Gralla, Urs Fischer

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Review article › Academic › peer-review

22 Citations (Scopus)

6 Downloads (Pure)

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.

Original language	English
Pages (from-to)	1073-1080
Number of pages	8
Journal	Journal of NeuroInterventional Surgery
Volume	13
Issue number	12
DOIs	https://doi.org/10.1136/neurintsurg-2020-016680
Publication status	Published - 1 Dec 2021

Bibliographical note

Funding Information:
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.

Funding Information:
Funding This work was supported by the Swiss Stroke Society, the Bangerter Foundation, and the Swiss Academy of Medical Sciences through the “Young Talents in Clinical Research” program.

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Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomyFinal published version, 1.45 MBLicence: CC BY-NC

Cite this

Kaesmacher, J., Meinel, T. R., Kurmann, C., Zaidat, O. O., Castonguay, A. C., Zaidi, S. F., Mueller-Kronast, N., Kappelhof, M., DIppel, DI. W. J., Soudant, M., Bracard, S., Hill, M. D., Goyal, M., Strbian, D., Heiferman, D. M., Ashley, W., Anadani, M., Spiotta, A. M., Dobrocky, T., ... Fischer, U. (2021). Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: A systematic review and meta-analysis of observational data. Journal of NeuroInterventional Surgery, 13(12), 1073-1080. https://doi.org/10.1136/neurintsurg-2020-016680

@article{10687fc41305457fbfcae4d7f1e9c55a,

title = "Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: A systematic review and meta-analysis of observational data",

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.",

author = "Johannes Kaesmacher and Meinel, {Thomas Raphael} and Christoph Kurmann and Zaidat, {Osama O.} and Castonguay, {Alicia C.} and Zaidi, {Syed F.} and Nils Mueller-Kronast and Manon Kappelhof and DIppel, {DIederik W.J.} and Marc Soudant and Serge Bracard and Hill, {Michael D.} and Mayank Goyal and Daniel Strbian and Heiferman, {Daniel M.} and William Ashley and Mohammad Anadani and Spiotta, {Alejandro M.} and Tomas Dobrocky and Piechowiak, {Eike I.} and Marcel Arnold and Martina Goeldlin and David Seiffge and Mosimann, {Pascal J.} and Pasquale Mordasini and Jan Gralla and Urs Fischer",

note = "Funding Information: 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 Nestl{\'e} 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{\textregistered}, 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. Funding Information: Funding This work was supported by the Swiss Stroke Society, the Bangerter Foundation, and the Swiss Academy of Medical Sciences through the “Young Talents in Clinical Research” program. Publisher Copyright: {\textcopyright} ",

year = "2021",

month = dec,

day = "1",

doi = "10.1136/neurintsurg-2020-016680",

language = "English",

volume = "13",

pages = "1073--1080",

number = "12",

}

Kaesmacher, J, Meinel, TR, Kurmann, C, Zaidat, OO, Castonguay, AC, Zaidi, SF, Mueller-Kronast, N, Kappelhof, M, DIppel, DIWJ, Soudant, M, Bracard, S, Hill, MD, Goyal, M, Strbian, D, Heiferman, DM, Ashley, W, Anadani, M, Spiotta, AM, Dobrocky, T, Piechowiak, EI, Arnold, M, Goeldlin, M, Seiffge, D, Mosimann, PJ, Mordasini, P, Gralla, J & Fischer, U 2021, 'Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: A systematic review and meta-analysis of observational data', Journal of NeuroInterventional Surgery, vol. 13, no. 12, pp. 1073-1080. https://doi.org/10.1136/neurintsurg-2020-016680

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: A systematic review and meta-analysis of observational data. / Kaesmacher, Johannes; Meinel, Thomas Raphael; Kurmann, Christoph et al.
In: Journal of NeuroInterventional Surgery, Vol. 13, No. 12, 01.12.2021, p. 1073-1080.

Research output: Contribution to journal › Review article › Academic › peer-review

TY - JOUR

T1 - Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy

T2 - A systematic review and meta-analysis of observational data

AU - Kaesmacher, Johannes

AU - Meinel, Thomas Raphael

AU - Kurmann, Christoph

AU - Zaidat, Osama O.

AU - Castonguay, Alicia C.

AU - Zaidi, Syed F.

AU - Mueller-Kronast, Nils

AU - Kappelhof, Manon

AU - DIppel, DIederik W.J.

AU - Soudant, Marc

AU - Bracard, Serge

AU - Hill, Michael D.

AU - Goyal, Mayank

AU - Strbian, Daniel

AU - Heiferman, Daniel M.

AU - Ashley, William

AU - Anadani, Mohammad

AU - Spiotta, Alejandro M.

AU - Dobrocky, Tomas

AU - Piechowiak, Eike I.

AU - Arnold, Marcel

AU - Goeldlin, Martina

AU - Seiffge, David

AU - Mosimann, Pascal J.

AU - Mordasini, Pasquale

AU - Gralla, Jan

AU - Fischer, Urs

N1 - Funding Information: 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. Funding Information: Funding This work was supported by the Swiss Stroke Society, the Bangerter Foundation, and the Swiss Academy of Medical Sciences through the “Young Talents in Clinical Research” program. Publisher Copyright: ©

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85100673852&partnerID=8YFLogxK

U2 - 10.1136/neurintsurg-2020-016680

DO - 10.1136/neurintsurg-2020-016680

M3 - Review article

C2 - 33514609

AN - SCOPUS:85100673852

VL - 13

SP - 1073

EP - 1080

IS - 12

ER -

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

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