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Intravenous Alteplase is Associated with First Pass Effect in Stent-retriever but not ADAPT Thrombectomy

Post Hoc Analysis of the SKIP Study

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Abstract

Purpose

To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke.

Methods

This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months.

Results

A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5–8.48) and in the ADAPT group it was 1.35 (0.37–4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37–0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups.

Conclusion

In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes.

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Funding

This study was supported by Japanese Society for Neuroendovascular Therapy (JSNET). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, National Hospital Organization Disaster Medical Center, Tokyo, Japan

    Keigo Shigeta, Masaya Enomoto, Jiro Aoyama & Tomoyuki Nakano

  2. Department of Neurology, Nippon Medical School Hospital, Tokyo, Japan

    Kentaro Suzuki & Kazumi Kimura

  3. Division of Stroke Prevention and Treatment, Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan

    Yuji Matsumaru & Mikito Hayakawa

  4. Department of Neurosurgery, Seisho Hospital, Kanagawa, Japan

    Masataka Takeuchi

  5. Department of Neurosurgery, Yokohama Shintoshi Neurosurgery Hospital, Kanagawa, Japan

    Masafumi Morimoto

  6. Department of Neurosurgery, Nagareyama Central Hospital, Chiba, Japan

    Ryuzaburo Kanazawa

  7. Department of Neurology, Akiyama Neurosurgical Hospital, Kanagawa, Japan

    Yohei Takayama

  8. Department of Neurology, Showa University Koto Toyosu Hospital, Tokyo, Japan

    Yuki Kamiya

  9. Department of Cerebrovascular Medicine, NTT Medical Center Tokyo, Tokyo, Japan

    Seiji Okubo

  10. Department of Neurosurgery, New Tokyo Hospital, Chiba, Japan

    Norihiro Ishii

  11. Department of Neurology and Neurosurgery, Chiba Emergency Medical Center, Chiba, Japan

    Yorio Koguchi

  12. Department of Neurosurgery, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan

    Takahiro Ota

  13. Department of Neurosurgery, Dokkyo Medical University Saitama Medical Center, Saitama, Japan

    Tomoji Takigawa

  14. Department of Neurosurgery, National Center for Global Health and Medicine, Tokyo, Japan

    Masato Inoue

  15. Department of Neurosurgery, Funabashi Municipal Medical Center, Chiba, Japan

    Hiromichi Naito

  16. Department of Stroke and Cerebrovascular Medicine, Kyorin University, Tokyo, Japan

    Teruyuki Hirano

  17. Department of Neurosurgery, Mito Medical Center, Ibaraki, Japan

    Noriyuki Kato

  18. Department of Strokology, Stroke Center, St. Marianna University Toyoko Hospital, Kanagawa, Japan

    Toshihiro Ueda

  19. Department of Neurosurgery, Mihara Memorial Hospital, Gunma, Japan

    Kazunori Akaji

  20. Department of Neurology, the Jikei University School of Medicine, Tokyo, Japan

    Yasuyuki Iguchi

  21. Department of Endovascular surgery, Tokyo Medical and Dental University, Tokyo, Japan

    Kazunori Miki

  22. Department of Endovascular Neurosurgery, Toranomon Hospital, Tokyo, Japan

    Wataro Tsuruta

  23. Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi, Japan

    Shigeru Fujimoto

Authors
  1. Keigo Shigeta
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  2. Kentaro Suzuki
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  3. Yuji Matsumaru
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  4. Masataka Takeuchi
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  5. Masafumi Morimoto
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  6. Ryuzaburo Kanazawa
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  7. Yohei Takayama
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  8. Yuki Kamiya
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  9. Seiji Okubo
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  10. Mikito Hayakawa
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  11. Norihiro Ishii
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  12. Yorio Koguchi
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  13. Takahiro Ota
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  14. Tomoji Takigawa
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  15. Masato Inoue
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  16. Hiromichi Naito
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  17. Teruyuki Hirano
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  18. Noriyuki Kato
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  19. Toshihiro Ueda
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  20. Kazunori Akaji
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  21. Yasuyuki Iguchi
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  22. Kazunori Miki
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  23. Wataro Tsuruta
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  24. Shigeru Fujimoto
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  25. Masaya Enomoto
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  26. Jiro Aoyama
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  27. Tomoyuki Nakano
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  28. Kazumi Kimura
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Consortia

SKIP study group

Contributions

Prof. Kazumi Kimura and Dr. Kentaro Suzuki had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The first (K. Shigeta) and last (KK) authors drafted the manuscript, and all authors contributed substantially to its revision. K. Shigeta analyzed the data. KK and K. Suzuki obtained research funding. K. Shigeta, K. Suzuki, YM, MT, MM, RK, YT, Y. Kamiya, SO, MH, NI, Y. Koguchi, TO, TT, MI, HN, NK, TU, KA, YI, KM, WT, ME, JA, TN, KK undertook recruitment of participating centers and patients and managed the data, including quality control. TH and SF served as an independent imaging committee. K. Shigeta takes responsibility for the paper as a whole.

Corresponding author

Correspondence to Keigo Shigeta.

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Conflict of interest

K. Shigeta, K. Suzuki, M. Morimoto, R. Kanazawa, Y. Takayama, S. Okubo, M. Hayakawa, N. Ishii, Y. Koguchi, T. Ota, T. Takigawa, M. Inoue, H. Naito, N. Kato, T. Ueda, K. Akaji, K. Miki, W. Tsuruta, S. Fujimoto, M. Enomoto, J. Aoyama and T. Nakano declare that they have no competing interests. K. Kimura received lecture fees from Bristol Myers Squibb, Nippon Boehringer Ingelheim, Bayer Healthcare, and Daiichi Sankyo; research funding from Nippon Boehringer Ingelheim, Daiichi Sankyo, Pfizer Japan, Medtronic, and Teijin Pharma; and personal funding from the 38th Mihara Cerebrovascular Disorder Research Promotion Fund. M. Takeuchi received lecture fees from Stryker. Shigeru Fujimoto received lecture fees from Nippon Boehringer Ingelheim, Daiichi Sankyo, Pfizer Japan, Bristol Myers Squibb Co. Ltd., Bayer Healthcare, and Takeda Pharmaceutical. T. Hirano received lecture fees from Bayer Healthcare, Daiichi Sankyo, Nippon Boehringer Ingelheim, Bristol Myers Squibb, Medtronic, Sanofi, Otsuka Pharmaceutical, Mitsubishi Tanabe Pharma, CSL Behring, Astellas Pharma, and Pfizer Japan. Y. Iguchi received lecture fees from Bayer Healthcare, Pfizer Japan, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Otsuka Pharmaceutical, and Daiichi Sankyo; and research funding from Sanofi. Y. Kamiya received lecture fees from Daiichi Sankyo; and research funding from Bristol Myers Squibb. Y. Matsumaru received lecture fees from Medtronic, Stryker, Sanofi, Daiichi Sankyo, Otsuka Pharmaceutical, and Biomedical solutions.

Ethical standards

The SKIP study was approved by the local institutional review boards, and written informed consent was obtained from all study participants. Because this study used existing anonymized information from the SKIP study, written informed consent from the study subjects was exempted in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subject in Japan. Consent to publish: not applicable.

Additional information

Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000024783:UMIN000021488

Availability of Data and Material

The data of this study are available from the corresponding author upon reasonable request.

Supplementary Information

62_2021_1085_MOESM1_ESM.docx

Online Resource 1. Patient baseline and clinical characteristics. Online Resource 2. Matched pair analysis of primary outcomes by subgroup

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Shigeta, K., Suzuki, K., Matsumaru, Y. et al. Intravenous Alteplase is Associated with First Pass Effect in Stent-retriever but not ADAPT Thrombectomy. Clin Neuroradiol 32, 153–162 (2022). https://doi.org/10.1007/s00062-021-01085-3

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