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  • Comparison of combined intravenous and intra-arterial thrombolysis with intravenous thrombolysis alone in stroke patients undergoing mechanical thrombectomy: a propensity-matched analysis

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Ischemic stroke
Original research
Comparison of combined intravenous and intra-arterial thrombolysis with intravenous thrombolysis alone in stroke patients undergoing mechanical thrombectomy: a propensity-matched analysis
  1. Sameh Samir Elawady1,
  2. Rahim Abo Kasem1,
  3. Bhageeradh Mulpur2,
  4. Conor Cunningham1,
  5. Hidetoshi Matsukawa1,3,
  6. Mohammad-Mahdi Sowlat1,
  7. Atakan Orscelik4,
  8. Noah L A Nawabi1,
  9. Julio Isidor1,
  10. Ilko Maier5,
  11. Pascal Jabbour6,
  12. Joon-tae Kim7,
  13. Stacey Q Wolfe8,
  14. Ansaar Rai9,
  15. Robert M Starke10,
  16. Marios-Nikos Psychogios11,
  17. Edgar A Samaniego12,
  18. Shinichi Yoshimura3,
  19. Hugo Cuellar13,
  20. Brian M Howard14,15,
  21. Ali Alawieh14,
  22. Ali Alaraj16,
  23. Mohamad Ezzeldin17,18,
  24. Daniele G Romano19,
  25. Omar Tanweer20,
  26. Justin R Mascitelli21,
  27. Isabel Fragata22,
  28. Adam J Polifka23,
  29. Fazeel Siddiqui24,
  30. Joshua W Osbun25,
  31. Ramesh Grandhi26,
  32. Roberto Javier Crosa27,
  33. Charles Matouk28,
  34. Min S Park29,
  35. Waleed Brinjikji30,
  36. Mark Moss31,
  37. Ergun Daglioglu32,
  38. Richard Williamson33,
  39. Pedro Navia34,
  40. Peter Kan35,
  41. Reade Andrew De Leacy36,
  42. Shakeel A Chowdhry37,
  43. David Altschul38,
  44. Alejandro M Spiotta1,
  45. Michael R Levitt39,
  46. Nitin Goyal2
    1. 1Department of Neurosurgery, Division of Neuroendovascular Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
    2. 2Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
    3. 3Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan
    4. 4Department of Neurosurgery, UCSF School of Medicine, San Francisco, California, USA
    5. 5Department of Neurology, University Medicine Goettingen, Goettingen, NS, Germany
    6. 6Department of Neurological surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    7. 7Department of Neurology, Chonnam National University Medical School, Gwangju, Gwangju, Korea (the Republic of)
    8. 8Department of Neurosurgery, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
    9. 9Department of Radiology, West Virginia University Hospitals, Morgantown, West Virginia, USA
    10. 10Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
    11. 11Department of Neuroradiology, Clinic of Radiology and Nuclear Medicine, University Hospital Basel, Basel, Switzerland
    12. 12Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
    13. 13Department of Neurosurgery, LSUHSC, Shreveport, Louisiana, USA
    14. 14Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA
    15. 15Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
    16. 16Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, USA
    17. 17Department of Clinical Sciences, College of Medicine, University of Houston, Houston, Texas, USA
    18. 18Department of Neuroendovascular surgery, HCA Houston, Houston, Texas, USA
    19. 19Department of Neurordiology, University Hospital 'San Giovanni di Dio e Ruggi d’Aragona', Salerno, Italy
    20. 20Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
    21. 21Deparment of Neurosurgery, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
    22. 22Department of Neuroradiology, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
    23. 23Department of Neurosurgery, University of Florida, Gainesville, Florida, USA
    24. 24Department of Neuroscience, University of Michigan Health-West, Wyoming, Wyoming, USA
    25. 25Department of Neurosurgery, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA
    26. 26Department of Neurosurgery, University of Utah Health, Salt Lake City, Utah, USA
    27. 27Department of Endovascular Neurosurgery, Médica Uruguaya, Montevideo, Montevideo, Uruguay
    28. 28Department of Neurosurgery, Yale University, New Haven, Connecticut, USA
    29. 29Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA
    30. 30Department of Radiology, Mayo Clinic Minnesota, Rochester, Minnesota, USA
    31. 31Department of Neuroradiology, Washington Regional J.B. Hunt Transport Services Neuroscience Institute, Fayetteville, Arizona, USA
    32. 32Department of Neurosurgery, Ankara Bilkent City Hospital, Ankara, Turkey
    33. 33Department of Neurology, Allegheny Health Network, Pittsburgh, Pennsylvania, USA
    34. 34Department of Interventional and Diagnostic Neuroradiology, Hospital Universitario La Paz, Madrid, Spain
    35. 35Department of Neurosurgery, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA
    36. 36Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
    37. 37Department of Neurosurgery, NorthShore University HealthSystem, Evanston, Illinois, USA
    38. 38Department of Neurosurgery, Montefiore Medical Center, Bronx, New York, USA
    39. 39Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington, USA
    1. Correspondence to Dr Alejandro M Spiotta; spiotta{at}musc.edu

    Abstract

    Background A combination of intravenous (IVT) or intra-arterial (IAT) thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) has been investigated. However, there is limited data on patients who receive both IVT and IAT compared with IVT alone before MT.

    Methods STAR data from 2013 to 2023 was utilized. We performed propensity score matching between the two groups. The primary outcomes were symptomatic intracranial hemorrhage (sICH) and 90-day modified Rankin Scale (mRS) score 0–2. Secondary outcomes included successful recanalization (modified treatment in cerebral infarction (mTICI) ≥2B, ≥2C), early neurological improvement, any intracranial hemorrhage (ICH), and 90-day mortality.

    Results A total of 2454 AIS-LVO patients were included. Propensity matching yielded 190 well-matched patients in each group. No significant differences were observed between the groups in either ICH or sICH (odds ratio (OR): 0.80, 95% confidence interval (CI) 0.51–1.24, P=0.37; OR: 0.60, 95% CI 0.29 to 1.24, P=0.21, respectively). Rates of successful recanalization and early neurological improvement (ENI) were significantly lower in MT+IVT + IAT. mRS 0–1 and mortality were not significantly different between the two groups. However, the MT+IVT + IAT group demonstrated superior rates of good functional outcomes (90-day mRS 0–1) compared with patients in the MT+IVT group who had mTICI ≤2B, (OR: 2.18, 95% CI 1.05 to 3.99, P=0.04).

    Conclusion The combined use of IAT and IVT thrombolysis in AIS-LVO patients undergoing MT is safe. Although the MT+IVT+ IAT group demonstrated lower rates of recanalization and early neurological improvement, long-term functional outcomes were favorable in this group suggesting a potential delayed benefit of IAT.

    • Stroke
    • Thrombolysis
    • Thrombectomy

    Data availability statement

    Data are available upon reasonable request. NA.

    https://doi.org/10.1136/jnis-2024-021975

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      Data availability statement

      Data are available upon reasonable request. NA.

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      Footnotes

      • SSE and RAK are joint first authors.

      • AMS, MRL and NG are joint senior authors.

      • X @mahdisowlat, @PascalJabbourMD, @Starke_neurosurgery, @BrianHoward_MD, @jmascite, @rocrossa, @pnavia, @PeterKa80460001, @rdeleacymd, @DavidAltschulMD, @DrMichaelLevitt

      • Contributors SSE, and RAK contributed equally to this paper. SSE: Conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the manuscript, and critical revision of the manuscript for important intellectual content. RAK: Conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the manuscript, and critical revision of the manuscript for important intellectual content. MRL: Conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the manuscript, and critical revision of the manuscript for important intellectual content. BM: Acquisition of data and critical revision of the manuscript for important intellectual content. CMC: Acquisition of data and critical revision of the manuscript for important intellectual content. HM : Acquisition of data and critical revision of the manuscript for important intellectual content. MMS : Acquisition of data and critical revision of the manuscript for important intellectual content. AO : Acquisition of data and critical revision of the manuscript for important intellectual content. NLAN : Acquisition of data and critical revision of the manuscript for important intellectual content. JI : Acquisition of data and critical revision of the manuscript for important intellectual content. Ilko M : Acquisition of data and critical revision of the manuscript for important intellectual content. PJ : Acquisition of data and critical revision of the manuscript for important intellectual content. JTK : Acquisition of data and critical revision of the manuscript for important intellectual content. SQW : Acquisition of data and critical revision of the manuscript for important intellectual content. AR : Acquisition of data and critical revision of the manuscript for important intellectual content. RMS : Acquisition of data and critical revision of the manuscript for important intellectual content. MNP : Acquisition of data and critical revision of the manuscript for important intellectual content. EAS : Acquisition of data and critical revision of the manuscript for important intellectual content. SY : Acquisition of data and critical revision of the manuscript for important intellectual content. HC : Acquisition of data and critical revision of the manuscript for important intellectual content. BH : Acquisition of data and critical revision of the manuscript for important intellectual content. AA : Acquisition of data and critical revision of the manuscript for important intellectual content. AA : Acquisition of data and critical revision of the manuscript for important intellectual content. ME: Acquisition of data and critical revision of the manuscript for important intellectual content. DGR : Acquisition of data and critical revision of the manuscript for important intellectual content. OT : Acquisition of data and critical revision of the manuscript for important intellectual content. JM : Acquisition of data and critical revision of the manuscript for important intellectual content. IF : Acquisition of data and critical revision of the manuscript for important intellectual content. AP : Acquisition of data and critical revision of the manuscript for important intellectual content. FS : Acquisition of data and critical revision of the manuscript for important intellectual content. JO : Acquisition of data and critical revision of the manuscript for important intellectual content. RG : Acquisition of data and critical revision of the manuscript for important intellectual content. RC : Acquisition of data and critical revision of the manuscript for important intellectual content. CM : Acquisition of data and critical revision of the manuscript for important intellectual content. MSP: Acquisition of data and critical revision of the manuscript for important intellectual content. WB: Acquisition of data and critical revision of the manuscript for important intellectual content. MM: Acquisition of data and critical revision of the manuscript for important intellectual content. ED: Acquisition of data and critical revision of the manuscript for important intellectual content. RW: Acquisition of data and critical revision of the manuscript for important intellectual content. PN: Acquisition of data and critical revision of the manuscript for important intellectual content. PK: Acquisition of data and critical revision of the manuscript for important intellectual content. RDL: Acquisition of data and critical revision of the manuscript for important intellectual content. SC: Acquisition of data and critical revision of the manuscript for important intellectual content. DJA: Acquisition of data and critical revision of the manuscript for important intellectual content. AMS: Conception and design of the study, overall supervision of the study, guarantor of the study, and final approval of the version to be published. NG: Conception and design of the study, overall supervision of the study, guarantor of the study, and final approval of the version to be published.

      • Funding This study was supported in STAR that receive research support from Penumbra, Microvention, Medtronic, Stryker, RapidAI, and Brain Aneurysm Foundation.The funding sources did not participate in any part of the study, from study conception to manuscript preparation.

      • Competing interests HM received a lecture fee from Daiichi-Sankyo and Stryker and consulting services fees from B Braun. ILM: speakers' honoraria from Pfizer and Bristol-Myers Squibb. RMS: research is supported by the NREF, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, Department of Health Biomedical Research Grant (21K02AWD-007000) and by National Institute of Health (R01NS111119-01A1) and (UL1TR002736, KL2TR002737) through the Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. RMS has an unrestricted research grant from Medtronic and Balt and has consulting and teaching agreements with Penumbra, Abbott, Medtronic, Balt, InNeuroCo, Cerenovus, Naglreiter, Tonbridge, Von Medical, and Optimize Vascular. MNP: Grants from the Swiss National Science Foundation (SNF) for the DISTAL trial (33IC30198783) and TECNO trial (32003B204977), Grant from Bangerter-Rhyner Stiftung for the DISTAL trial. Unrestricted Grants for the DISTAL trial from Stryker Neurovascular Inc., Phenox GmbH, Penumbra Inc., and Rapid Medical Inc., Sponsor-PI SPINNERS trial (Funded by a Siemens Healthineers AG Grant), Research agreement with Siemens Healthineers AG, Local PI for the ASSIST, EXCELLENT, TENSION, COATING, SURF, and ESCAPE-NEXT trials. Speaker fees: Stryker Neurovascular Inc., Medtronic Inc., Penumbra Inc., Acandis GmbH, Phenox GmbH, Siemens Healthineers AG. ES: consults for Medtronic, Microvention, Rapid Medical. SY: received lecture fees from Stryker, Medtronic, Johnson & Johnson, Kaneka Medics. HC: Consultant for Medtronic and Microvention. JAG: Georgia Research Alliance, Emory Medical Care Foundation, Neurosurgery Catalyst, Consultant: Cognition, Imperative Care. DGR: Consultant for Penumbra, Balt, Microvention, Phenox. OT: Consulting Agreements: Viz.AI, Inc., Penumbra, Inc, Balt, Inc, Stryker Inc, Imperative Inc. Proctor: Microvention Inc, Medtronic Inc. Educational/Research Grants: Q’apel Inc, Steinberg Foundation. CM: Consultant for Stryker, Medtronic, Microvention, Penumbra, and Silk Road Medical. Speaker for Penumbra and Silk Road Medical. Contact PI for NIH Grant R21NS128641. MSP: Consultant for Medtronic. MRL: Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Medtronic, Aeaean Advisers and Metis Innovative; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. WB: Holds equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular. He receives royalties from Medtronic and Balloon Guide Catheter Technology. He receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt. He serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (Editor in Chief), Piraeus Medical, and WFITN. RW: Consultant for Medtronic, Stryker, and Synaptive Medical. PN: Consultant for Penumbra, Medtronic, Stryker, Cerenovus, and Balt. PK: Grants from the NIH (1U18EB029353-01) and unrestricted educational grants from Medtronic and Siemens. Consultant for Imperative Care and Stryker Neurovascular. Stock ownership in Vena Medical. RDL: PI for Imperative Trial; Research grants from Siemens Healthineers and Kaneka medical. Consultant for Cerenovus, Stryker Neurovascular and Sim & Cure. Minor equity interest Vastrax, Borvo medical, Synchron, Endostream, Von Vascular, Radical catheters, and Precision Recovery Inc. SAC: Consultant and proctor for Medtronic and Microvention. ME: Consultant for Viz.ai and Imperative care. Investments in Galaxy Therapeutics. DJA: Consultant for MicroVention, Stryker, and Cerenovus. RG: Consultant for Balt Neurovascular, Cerenovus, Medtronic Neurovascular, Rapid Medical, and Stryker Neurovascular. AMS: Consultant for Penumbra, Terumo, RapidAI, Cerenovus. AA: Consultant for Cerenovus. SSE, RAK, BM, CMC, MMS, AO, NLN, JI, PJ, JTK, SQW, AR, AA, JM, IF, AP, FS, JO, RC, MM, ED, NG: none.

      • Provenance and peer review Not commissioned; externally peer reviewed.

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