Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets

Georgios Tsivgoulis; Aristeidis H. Katsanos; Dimitris Mavridis; Zuzana Gdovinova; Michał Karliński; Mary Joan Macleod; Daniel Strbian; Niaz Ahmed

doi:10.1002/ana.25269

Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets

Georgios Tsivgoulis^*, Aristeidis H. Katsanos, Dimitris Mavridis, Zuzana Gdovinova, Michał Karliński, Mary Joan Macleod, Daniel Strbian, Niaz Ahmed

^*Corresponding author for this work

Applied Medicine

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Abstract

Objective: We assessed the outcomes of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients on dual antiplatelet therapy prior to stroke onset. Methods: We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register on consecutive IVT-treated AIS patients during a 7-year period (2010–2017). In propensity score matched groups of patients with dual antiplatelet pretreatment and no antiplatelet pretreatment, we compared: (1) symptomatic intracerebral hemorrhage (SICH), according to SITS Monitoring Study (MOST), European Cooperative Acute Stroke Study (ECASS) II, and National Institute of Neurological Disorders and Stroke (NINDS) definitions; (2) 3-month mortality; (3) 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores = 0–1); (4) 3-month functional independence (FI; mRS scores = 0–2); and (5) distribution of the 3-month mRS scores. Dual antiplatelet pretreatment was defined as all possible combinations among aspirin, clopidogrel, dipyridamole, and any other antiplatelet. Results: Propensity score matching resulted in 2 groups of 1,043 patients each, balanced for all baseline characteristics. In the propensity score matched analysis, the 2 groups had comparable (p > 0.017 using Bonferroni correction for multiple comparisons) SICH rates according to SITS-MOST (2.9% vs 1.5%, 95% confidence interval [CI] = −0.03 to −0.01), ECASS II (5.2% vs 4.4%, 95% CI = −0.03 to 0.01), and NINDS (7.7% vs 6.6%, 95% CI = −0.03 to 0.01) definitions. No differences in the 3-month mortality (17.9% vs 16.6%, 95% CI = −0.05 to 0.02), FFO (45.6% vs 46.0%, 95% CI = −0.04 to 0.05), FI (59.2% vs 60.7%, 95% CI = −0.03 to 0.06), or distribution in 3-month mRS scores (2 [1–4] vs 2 [0–4], 95% CI = −0.29 to 0.09) were documented between the 2 groups. Interpretation: Given that patients on dual antiplatelet pretreatment have similar SICH, 3-month mortality rates, and functional outcomes compared to patients with no antiplatelet pretreatment, dual antiplatelet pretreatment history should not be used as a reason to withhold IVT in otherwise eligible AIS patients. Ann Neurol 2018;83:89–97.

Original language	English
Pages (from-to)	89-97
Number of pages	9
Journal	Annals of Neurology
Volume	84
Issue number	1
Early online date	30 Jul 2018
DOIs	https://doi.org/10.1002/ana.25269
Publication status	Published - Jul 2018

Bibliographical note

Funding Information:
The current SITS registry is developed, maintained, and upgraded by ZiteLab, Copenhagen, Denmark, in close collaboration with SITS. SITS is financed directly and indirectly by grants from the Karolinska Institute, Stockholm County Council, Swedish Heart-Lung Foundation, Swedish Order of St John, Friends of Karolinska Institute, and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, and Ferrer International. SITS is currently conducting studies supported by Boehringer Ingelheim and EVER Pharma, as well as in collaboration with the Karolinska Institute, supported by Stryker, Covidien, and Phenox. N.A. is supported by grants provided by the Stockholm County Council and Swedish Heart-Lung Foundation. No funding sources had a part in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. We thank all SITS-ISTR investigators and their centers for their participation; and all patients who participated in SITS-ISTR.

Funding Information:
The current SITS registry is developed, maintained, and upgraded by ZiteLab, Copenhagen, Denmark, in close collaboration with SITS. SITS is financed directly and indirectly by grants from the Karolinska Institute, Stockholm County Council, Swedish Heart-Lung Foundation, Swedish Order of St John, Friends of Karolinska Institute, and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, and Ferrer International. SITS is currently conducting studies supported by Boehringer Ingelheim and EVER Pharma, as well as in collaboration with the Karolinska Institute, supported by Stryker, Covidien, and Phenox. N.A. is supported by grants provided by the Stockholm County Council and Swedish Heart-Lung Foundation. No funding sources had a part in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Publisher Copyright:
© 2018 American Neurological Association

Keywords

acute ischemic stroke
dual antiplatelet therapy
mortality
functional outcome
intracranial hemorrhage

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Tsivgoulis_etal_AN_Intravenous_Thrombolysis_Ischemic_AAM
This is the peer reviewed version of the following article: Tsivgoulis, G. , Katsanos, A. H., Mavridis, D. , Gdovinova, Z. , Karliński, M. , Macleod, M. J., Strbian, D. and Ahmed, N. (2018), Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets. Ann Neurol., 84: 89-97, which has been published in final form at https://doi.org/10.1002/ana.25269. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Accepted author manuscript, 231 KBLicence: Unspecified

Cite this

@article{c87e80537662494fbf34fceefe7e3cdd,

title = "Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets",

abstract = "Objective: We assessed the outcomes of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients on dual antiplatelet therapy prior to stroke onset. Methods: We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register on consecutive IVT-treated AIS patients during a 7-year period (2010–2017). In propensity score matched groups of patients with dual antiplatelet pretreatment and no antiplatelet pretreatment, we compared: (1) symptomatic intracerebral hemorrhage (SICH), according to SITS Monitoring Study (MOST), European Cooperative Acute Stroke Study (ECASS) II, and National Institute of Neurological Disorders and Stroke (NINDS) definitions; (2) 3-month mortality; (3) 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores = 0–1); (4) 3-month functional independence (FI; mRS scores = 0–2); and (5) distribution of the 3-month mRS scores. Dual antiplatelet pretreatment was defined as all possible combinations among aspirin, clopidogrel, dipyridamole, and any other antiplatelet. Results: Propensity score matching resulted in 2 groups of 1,043 patients each, balanced for all baseline characteristics. In the propensity score matched analysis, the 2 groups had comparable (p > 0.017 using Bonferroni correction for multiple comparisons) SICH rates according to SITS-MOST (2.9% vs 1.5%, 95% confidence interval [CI] = −0.03 to −0.01), ECASS II (5.2% vs 4.4%, 95% CI = −0.03 to 0.01), and NINDS (7.7% vs 6.6%, 95% CI = −0.03 to 0.01) definitions. No differences in the 3-month mortality (17.9% vs 16.6%, 95% CI = −0.05 to 0.02), FFO (45.6% vs 46.0%, 95% CI = −0.04 to 0.05), FI (59.2% vs 60.7%, 95% CI = −0.03 to 0.06), or distribution in 3-month mRS scores (2 [1–4] vs 2 [0–4], 95% CI = −0.29 to 0.09) were documented between the 2 groups. Interpretation: Given that patients on dual antiplatelet pretreatment have similar SICH, 3-month mortality rates, and functional outcomes compared to patients with no antiplatelet pretreatment, dual antiplatelet pretreatment history should not be used as a reason to withhold IVT in otherwise eligible AIS patients. Ann Neurol 2018;83:89–97.",

keywords = "acute ischemic stroke, dual antiplatelet therapy, mortality, functional outcome, intracranial hemorrhage",

author = "Georgios Tsivgoulis and Katsanos, {Aristeidis H.} and Dimitris Mavridis and Zuzana Gdovinova and Micha{\l} Karli{\'n}ski and Macleod, {Mary Joan} and Daniel Strbian and Niaz Ahmed",

note = "Funding Information: The current SITS registry is developed, maintained, and upgraded by ZiteLab, Copenhagen, Denmark, in close collaboration with SITS. SITS is financed directly and indirectly by grants from the Karolinska Institute, Stockholm County Council, Swedish Heart-Lung Foundation, Swedish Order of St John, Friends of Karolinska Institute, and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, and Ferrer International. SITS is currently conducting studies supported by Boehringer Ingelheim and EVER Pharma, as well as in collaboration with the Karolinska Institute, supported by Stryker, Covidien, and Phenox. N.A. is supported by grants provided by the Stockholm County Council and Swedish Heart-Lung Foundation. No funding sources had a part in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. We thank all SITS-ISTR investigators and their centers for their participation; and all patients who participated in SITS-ISTR. Funding Information: The current SITS registry is developed, maintained, and upgraded by ZiteLab, Copenhagen, Denmark, in close collaboration with SITS. SITS is financed directly and indirectly by grants from the Karolinska Institute, Stockholm County Council, Swedish Heart-Lung Foundation, Swedish Order of St John, Friends of Karolinska Institute, and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, and Ferrer International. SITS is currently conducting studies supported by Boehringer Ingelheim and EVER Pharma, as well as in collaboration with the Karolinska Institute, supported by Stryker, Covidien, and Phenox. N.A. is supported by grants provided by the Stockholm County Council and Swedish Heart-Lung Foundation. No funding sources had a part in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2018 American Neurological Association",

year = "2018",

month = jul,

doi = "10.1002/ana.25269",

language = "English",

volume = "84",

pages = "89--97",

journal = "Annals of Neurology",

issn = "0364-5134",

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number = "1",

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TY - JOUR

T1 - Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets

AU - Tsivgoulis, Georgios

AU - Katsanos, Aristeidis H.

AU - Mavridis, Dimitris

AU - Gdovinova, Zuzana

AU - Karliński, Michał

AU - Macleod, Mary Joan

AU - Strbian, Daniel

AU - Ahmed, Niaz

N1 - Funding Information: The current SITS registry is developed, maintained, and upgraded by ZiteLab, Copenhagen, Denmark, in close collaboration with SITS. SITS is financed directly and indirectly by grants from the Karolinska Institute, Stockholm County Council, Swedish Heart-Lung Foundation, Swedish Order of St John, Friends of Karolinska Institute, and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, and Ferrer International. SITS is currently conducting studies supported by Boehringer Ingelheim and EVER Pharma, as well as in collaboration with the Karolinska Institute, supported by Stryker, Covidien, and Phenox. N.A. is supported by grants provided by the Stockholm County Council and Swedish Heart-Lung Foundation. No funding sources had a part in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. We thank all SITS-ISTR investigators and their centers for their participation; and all patients who participated in SITS-ISTR. Funding Information: The current SITS registry is developed, maintained, and upgraded by ZiteLab, Copenhagen, Denmark, in close collaboration with SITS. SITS is financed directly and indirectly by grants from the Karolinska Institute, Stockholm County Council, Swedish Heart-Lung Foundation, Swedish Order of St John, Friends of Karolinska Institute, and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, and Ferrer International. SITS is currently conducting studies supported by Boehringer Ingelheim and EVER Pharma, as well as in collaboration with the Karolinska Institute, supported by Stryker, Covidien, and Phenox. N.A. is supported by grants provided by the Stockholm County Council and Swedish Heart-Lung Foundation. No funding sources had a part in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Publisher Copyright: © 2018 American Neurological Association

PY - 2018/7

Y1 - 2018/7

N2 - Objective: We assessed the outcomes of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients on dual antiplatelet therapy prior to stroke onset. Methods: We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register on consecutive IVT-treated AIS patients during a 7-year period (2010–2017). In propensity score matched groups of patients with dual antiplatelet pretreatment and no antiplatelet pretreatment, we compared: (1) symptomatic intracerebral hemorrhage (SICH), according to SITS Monitoring Study (MOST), European Cooperative Acute Stroke Study (ECASS) II, and National Institute of Neurological Disorders and Stroke (NINDS) definitions; (2) 3-month mortality; (3) 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores = 0–1); (4) 3-month functional independence (FI; mRS scores = 0–2); and (5) distribution of the 3-month mRS scores. Dual antiplatelet pretreatment was defined as all possible combinations among aspirin, clopidogrel, dipyridamole, and any other antiplatelet. Results: Propensity score matching resulted in 2 groups of 1,043 patients each, balanced for all baseline characteristics. In the propensity score matched analysis, the 2 groups had comparable (p > 0.017 using Bonferroni correction for multiple comparisons) SICH rates according to SITS-MOST (2.9% vs 1.5%, 95% confidence interval [CI] = −0.03 to −0.01), ECASS II (5.2% vs 4.4%, 95% CI = −0.03 to 0.01), and NINDS (7.7% vs 6.6%, 95% CI = −0.03 to 0.01) definitions. No differences in the 3-month mortality (17.9% vs 16.6%, 95% CI = −0.05 to 0.02), FFO (45.6% vs 46.0%, 95% CI = −0.04 to 0.05), FI (59.2% vs 60.7%, 95% CI = −0.03 to 0.06), or distribution in 3-month mRS scores (2 [1–4] vs 2 [0–4], 95% CI = −0.29 to 0.09) were documented between the 2 groups. Interpretation: Given that patients on dual antiplatelet pretreatment have similar SICH, 3-month mortality rates, and functional outcomes compared to patients with no antiplatelet pretreatment, dual antiplatelet pretreatment history should not be used as a reason to withhold IVT in otherwise eligible AIS patients. Ann Neurol 2018;83:89–97.

AB - Objective: We assessed the outcomes of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients on dual antiplatelet therapy prior to stroke onset. Methods: We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register on consecutive IVT-treated AIS patients during a 7-year period (2010–2017). In propensity score matched groups of patients with dual antiplatelet pretreatment and no antiplatelet pretreatment, we compared: (1) symptomatic intracerebral hemorrhage (SICH), according to SITS Monitoring Study (MOST), European Cooperative Acute Stroke Study (ECASS) II, and National Institute of Neurological Disorders and Stroke (NINDS) definitions; (2) 3-month mortality; (3) 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores = 0–1); (4) 3-month functional independence (FI; mRS scores = 0–2); and (5) distribution of the 3-month mRS scores. Dual antiplatelet pretreatment was defined as all possible combinations among aspirin, clopidogrel, dipyridamole, and any other antiplatelet. Results: Propensity score matching resulted in 2 groups of 1,043 patients each, balanced for all baseline characteristics. In the propensity score matched analysis, the 2 groups had comparable (p > 0.017 using Bonferroni correction for multiple comparisons) SICH rates according to SITS-MOST (2.9% vs 1.5%, 95% confidence interval [CI] = −0.03 to −0.01), ECASS II (5.2% vs 4.4%, 95% CI = −0.03 to 0.01), and NINDS (7.7% vs 6.6%, 95% CI = −0.03 to 0.01) definitions. No differences in the 3-month mortality (17.9% vs 16.6%, 95% CI = −0.05 to 0.02), FFO (45.6% vs 46.0%, 95% CI = −0.04 to 0.05), FI (59.2% vs 60.7%, 95% CI = −0.03 to 0.06), or distribution in 3-month mRS scores (2 [1–4] vs 2 [0–4], 95% CI = −0.29 to 0.09) were documented between the 2 groups. Interpretation: Given that patients on dual antiplatelet pretreatment have similar SICH, 3-month mortality rates, and functional outcomes compared to patients with no antiplatelet pretreatment, dual antiplatelet pretreatment history should not be used as a reason to withhold IVT in otherwise eligible AIS patients. Ann Neurol 2018;83:89–97.

KW - acute ischemic stroke

KW - dual antiplatelet therapy

KW - mortality

KW - functional outcome

KW - intracranial hemorrhage

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AN - SCOPUS:85051028869

SN - 0364-5134

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JO - Annals of Neurology

JF - Annals of Neurology

IS - 1

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Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets

Abstract

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Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets

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