TY - JOUR
T1 - Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke
AU - Vos, E. M.
AU - Geraedts, V. J.
AU - van der Lugt, A.
AU - Dippel, D. W. J.
AU - Wermer, M. J. H.
AU - Hofmeijer, J.
AU - van Es, A. C. G. M.
AU - Roos, Y. B. W. E. M.
AU - Peeters-Scholte, C. M. P. C. D.
AU - van den Wijngaard, I. R.
N1 - Funding Information: This open access publication fee was funded by a grant from the Research Fund of Haaglanden Medisch Centrum. Funding Information: We thank I. de Boer, MD, MSc, Department of Neurology, Leiden University Medical Center, for assistance in graphical abstract design. Funding Information: CP-S is founder and consultant at Neurophyxia BV. She holds several patents and stocks of Neurophyxia BV. DD received grants from Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Stryker, Penumbra, Inc, Medtronic, Thrombolytic Science LLC, and Ceronovus. YR is a shareholder at Nicolab B.V. AL received grants from Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Stryker, Penumbra, Inc, Medtronic, Thrombolytic Science LLC, and Ceronovus. MJHW received grants from Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development and an unrestricted research grant from Electrocore. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher Copyright: Copyright © 2022 Vos, Geraedts, van der Lugt, Dippel, Wermer, Hofmeijer, van Es, Roos, Peeters-Scholte and van den Wijngaard.
PY - 2022/3/17
Y1 - 2022/3/17
N2 - Background: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS. Methods: A literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included. Results: We screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT. Conclusion: Studies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.
AB - Background: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS. Methods: A literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included. Results: We screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT. Conclusion: Studies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.
KW - intravenous thrombolysis
KW - neuroprotection
KW - reperfusion after ischemia
KW - stroke
KW - thrombectomy
UR - http://www.scopus.com/inward/record.url?scp=85127800642&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fneur.2022.840892
DO - https://doi.org/10.3389/fneur.2022.840892
M3 - Review article
C2 - 35370911
SN - 1664-2295
VL - 13
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 840892
ER -