Observational Study

. 2021 Dec;30(12):106121.

doi: 10.1016/j.jstrokecerebrovasdis.2021.106121. Epub 2021 Sep 20.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative

Payam Sasanejad¹, Leila Afshar Hezarkhani², Shahram Arsang-Jang³, Georgios Tsivgoulis⁴, Abdoreza Ghoreishi⁵, Kristian Barlinn⁶, Jan Rahmig⁷, Mehdi Farhoudi⁸, Elyar Sadeghi Hokmabadi⁹, Afshin Borhani-Haghighi¹⁰, Payam Sariaslani¹¹, Athena Sharifi-Razavi¹², Kavian Ghandehari¹³, Alireza Khosravi¹⁴, Craig Smith¹⁵, Yongchai Nilanont¹⁶, Yama Akbari¹⁷, Thanh N Nguyen¹⁸, Anna Bersano¹⁹, Nawaf Yassi²⁰, Takeshi Yoshimoto²¹, Simona Lattanzi²², Animesh Gupta²³, Ramin Zand²⁴, Shahram Rafie²⁵, Seyede Pourandokht Mousavian²⁶, Mohammad Reza Shahsavaripour²⁶, Shahram Amini²⁷, Saltanat U Kamenova²⁸, Aida Kondybayeva²⁹, Murat Zhanuzakov³⁰, Elizabeth M Macri³¹, Christa O'Hana S Nobleza³², Sean Ruland³³, Anna M Cervantes-Arslanian³⁴, Masoom J Desai³⁵, Annemarei Ranta³⁶, Amir Moghadam Ahmadi³⁷, Mahtab Rostamihosseinkhani¹⁰, Razieh Foroughi¹⁰, Etrat Hooshmandi¹⁰, Fahimeh H Akhoundi³⁸, Ashfaq Shuaib³⁹, David S Liebeskind⁴⁰, James Siegler⁴¹, Jose G Romano⁴², Stephan A Mayer⁴³, Reza Bavarsad Shahripour⁴⁴, Babak Zamani⁴⁵, Amadene Woolsey⁴⁶, Yasaman Fazli⁴⁷, Khazaei Mojtaba⁴⁸, Christian F Isaac⁴⁹, Jose Biller⁵⁰, Mario Di Napoli⁵¹, M Reza Azarpazhooh⁵²

Affiliations

¹ Department of Neurology Mashhad Fellowship of interventional radiology Mashhad University of Medical Sciences. Electronic address: reza.azarpazhooh@lhsc.on.ca.
² Department of Neurology School of Medicine Farabi Hospital Kermanshah University of Medical Sciences, Kermanshah, Iran.
³ Department of Biostatistics and Epidemiology School of Medicine Zanjan University of Medical Sciences, Zanjan, Iran.
⁴ Second Department of Neurology National & Kapodistrian University of Athens,Professor of Neurology, Athens, Greece.
⁵ Department of Neurology, Vali-e-Asr Hospital, School of Medicine, Zanjan University of Medical Sciences.
⁶ University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden.
⁷ Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁸ Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
⁹ Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz.
¹⁰ Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
¹¹ Department of Neurology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
¹² Clinical Research Development Unit of Bou-Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
¹³ Department of Neurology Mashhad University of Medical Sciences, Mashhad, Iran.
¹⁴ Clinical Immunology Research Center, Department of Neurology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
¹⁵ Manchester Centre for Clinical Neurosciences, Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, UK; Division of Cardiovascular Sciences, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK.
¹⁶ Siriraj Stroke Center, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
¹⁷ Departments of Neurology, Neurological Surgery, and Anatomy & Neurobiology, and Beckman Laser Institute & Medical Clinic, School of Medicine, University of California, Irvine, CA, USA.
¹⁸ Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
¹⁹ Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico carlo Besta, Milano, Italy.
²⁰ Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
²¹ Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
²² Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca, Ancona, Italy.
²³ Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA.
²⁴ Department of Neurology, Neuroscience Institute, Geisinger Medical Center, Danville, PA, USA.
²⁵ Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
²⁶ Department of Neurology, Mashhad University of Medical Sciences, Mashhad, Iran.
²⁷ Department of Anesthesia, Intensive care Unit, Lung Research Center, Mashhad, Mashhad University of Medical Sciences.
²⁸ Department of Medicine, Al-Farabi Kazakh National University, Doctor of Medical Science, Professor. Almaty, Kazakhstan.
²⁹ Doctor of Medical Science, Professor Doctor of Medical Science, Professor, Department of Medicine, Al-Farabi Kazakh National University. Almaty, Kazakhstan.
³⁰ Doctor of Medical Science Professor, Department of Internal Medicine, Kazakh-Russian Medical University. Almaty, Kazakhstan.
³¹ Department of Neurology, University of New Mexico, Albuquerque, NM.
³² Department of Neurology, University of Mississippi Medical Center, Jackson, MS.
³³ Department of Neurology, Loyola University Chicago-Stritch School of Medicine, Chicago, IL.
³⁴ Departments of Neurology, Neurosurgery, and Medicine (Infectious Disease), Boston University School of Medicine, Boston Medical Center, Boston, MA.
³⁵ Assistant Professor of Neurology, University of New Mexico, Albuquerque.
³⁶ Department of Medicine, University of Otago, Wellington and Department of Neurology, Wellington Regional Hospital, New Zealand.
³⁷ Associate Professor of Neurology, School of Medicine, Non-communicable Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
³⁸ Department of Neurology, Iran University of medical Sciences, Tehran, Iran.
³⁹ Professor of Neurology and Director Stroke Program University of Alberta, Alberta, Canada.
⁴⁰ UCLA Stroke Center, Los Angeles, CA, USA.
⁴¹ Cooper Neurological Institute, Cooper University Hospital, Camden, NJ.
⁴² Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA.
⁴³ Professor of Neurology and Neurosurgery, New York Medical College, Westchester Medical Center, Valhalla, NY.
⁴⁴ University of California San Diego Neurosciences center, Comprehensive Stroke center, San Diego, CA.
⁴⁵ Department of Neurology, Iran University of Medical Sciences, Tehran, Iran.
⁴⁶ Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada. Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.
⁴⁷ School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴⁸ Assistant Professor of Neurology, Assistant Professor of Neurology, Hamadan Medical University of Medical Sciences, Fellowship of neurovascular intervention.
⁴⁹ Department of Neurology, Hospital Dr Arturo Oñativia, Argentina.
⁵⁰ Department of Neurology, Loyola University Health System, Stritch School of Medicine, Chicago, IL, USA.
⁵¹ Department of Neurology and Stroke Unit, San Camillo de' Lellis General District Hospital, Rieti, Italy; Neurological Section, Neuro-epidemiology Unit, SMDN-Centre for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, L'Aquila, Italy.
⁵² Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada; Department of Clinical Neurological Sciences, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.

PMID: 34601242
PMCID: PMC8450304
DOI: 10.1016/j.jstrokecerebrovasdis.2021.106121

Observational Study

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative

Payam Sasanejad et al. J Stroke Cerebrovasc Dis. 2021 Dec.

. 2021 Dec;30(12):106121.

doi: 10.1016/j.jstrokecerebrovasdis.2021.106121. Epub 2021 Sep 20.

Authors

Affiliations

¹ Department of Neurology Mashhad Fellowship of interventional radiology Mashhad University of Medical Sciences. Electronic address: reza.azarpazhooh@lhsc.on.ca.
² Department of Neurology School of Medicine Farabi Hospital Kermanshah University of Medical Sciences, Kermanshah, Iran.
³ Department of Biostatistics and Epidemiology School of Medicine Zanjan University of Medical Sciences, Zanjan, Iran.
⁴ Second Department of Neurology National & Kapodistrian University of Athens,Professor of Neurology, Athens, Greece.
⁵ Department of Neurology, Vali-e-Asr Hospital, School of Medicine, Zanjan University of Medical Sciences.
⁶ University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden.
⁷ Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁸ Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
⁹ Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz.
¹⁰ Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
¹¹ Department of Neurology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
¹² Clinical Research Development Unit of Bou-Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
¹³ Department of Neurology Mashhad University of Medical Sciences, Mashhad, Iran.
¹⁴ Clinical Immunology Research Center, Department of Neurology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
¹⁵ Manchester Centre for Clinical Neurosciences, Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, UK; Division of Cardiovascular Sciences, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK.
¹⁶ Siriraj Stroke Center, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
¹⁷ Departments of Neurology, Neurological Surgery, and Anatomy & Neurobiology, and Beckman Laser Institute & Medical Clinic, School of Medicine, University of California, Irvine, CA, USA.
¹⁸ Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
¹⁹ Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico carlo Besta, Milano, Italy.
²⁰ Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
²¹ Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
²² Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca, Ancona, Italy.
²³ Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA.
²⁴ Department of Neurology, Neuroscience Institute, Geisinger Medical Center, Danville, PA, USA.
²⁵ Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
²⁶ Department of Neurology, Mashhad University of Medical Sciences, Mashhad, Iran.
²⁷ Department of Anesthesia, Intensive care Unit, Lung Research Center, Mashhad, Mashhad University of Medical Sciences.
²⁸ Department of Medicine, Al-Farabi Kazakh National University, Doctor of Medical Science, Professor. Almaty, Kazakhstan.
²⁹ Doctor of Medical Science, Professor Doctor of Medical Science, Professor, Department of Medicine, Al-Farabi Kazakh National University. Almaty, Kazakhstan.
³⁰ Doctor of Medical Science Professor, Department of Internal Medicine, Kazakh-Russian Medical University. Almaty, Kazakhstan.
³¹ Department of Neurology, University of New Mexico, Albuquerque, NM.
³² Department of Neurology, University of Mississippi Medical Center, Jackson, MS.
³³ Department of Neurology, Loyola University Chicago-Stritch School of Medicine, Chicago, IL.
³⁴ Departments of Neurology, Neurosurgery, and Medicine (Infectious Disease), Boston University School of Medicine, Boston Medical Center, Boston, MA.
³⁵ Assistant Professor of Neurology, University of New Mexico, Albuquerque.
³⁶ Department of Medicine, University of Otago, Wellington and Department of Neurology, Wellington Regional Hospital, New Zealand.
³⁷ Associate Professor of Neurology, School of Medicine, Non-communicable Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
³⁸ Department of Neurology, Iran University of medical Sciences, Tehran, Iran.
³⁹ Professor of Neurology and Director Stroke Program University of Alberta, Alberta, Canada.
⁴⁰ UCLA Stroke Center, Los Angeles, CA, USA.
⁴¹ Cooper Neurological Institute, Cooper University Hospital, Camden, NJ.
⁴² Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA.
⁴³ Professor of Neurology and Neurosurgery, New York Medical College, Westchester Medical Center, Valhalla, NY.
⁴⁴ University of California San Diego Neurosciences center, Comprehensive Stroke center, San Diego, CA.
⁴⁵ Department of Neurology, Iran University of Medical Sciences, Tehran, Iran.
⁴⁶ Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada. Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.
⁴⁷ School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴⁸ Assistant Professor of Neurology, Assistant Professor of Neurology, Hamadan Medical University of Medical Sciences, Fellowship of neurovascular intervention.
⁴⁹ Department of Neurology, Hospital Dr Arturo Oñativia, Argentina.
⁵⁰ Department of Neurology, Loyola University Health System, Stritch School of Medicine, Chicago, IL, USA.
⁵¹ Department of Neurology and Stroke Unit, San Camillo de' Lellis General District Hospital, Rieti, Italy; Neurological Section, Neuro-epidemiology Unit, SMDN-Centre for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, L'Aquila, Italy.
⁵² Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada; Department of Clinical Neurological Sciences, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.

PMID: 34601242
PMCID: PMC8450304
DOI: 10.1016/j.jstrokecerebrovasdis.2021.106121

Abstract

Background: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19.

Methods: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes.

Results: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054).

Conclusion: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Keywords: COVID-19; Disability; Longitudinal study; Outcomes; Safety; Stroke; Stroke severity; Thrombolytic therapy; death.

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Conflict of interest statement

Declaration of Competing Interest Authors reports no disclosures.

Figures

**Fig. 1**
Diagnostic ability of High-sensitivity C reactive protein to predict mortality and hemorrhagic transformation among individuals with COVID-19.

See this image and copyright information in PMC

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Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative

Affiliations

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

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LinkOut - more resources

Full Text Sources

Medical

Research Materials