Microbleeds and the Effect of Anticoagulation in Patients With
Embolic Stroke of Undetermined Source An Exploratory Analysis
of the NAVIGATE ESUS Randomized Clinical Trial

J 2021

Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial

SHOAMANESH, A., R. G. HART, S. J. CONNOLLY, SE KASNER, E. E. SMITH et. al.

Basic information

Original name

Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial

Authors

SHOAMANESH, A. (guarantor), R. G. HART, S. J. CONNOLLY, SE KASNER, E. E. SMITH, J. MARTI-FABREGAS, Y. Y. LIU, S. UCHIYAMA, Robert MIKULÍK (203 Czech Republic, belonging to the institution), R. VELTKAMP, M. J. O DONNELL, G. NTAIOS, K. W. MUIR, T. S. FIELD, G. C. SANTO, V. OLAVARRIA, H. MUNDL, H. LUTSEP, S. D. BERKOWITZ and M. SHARMA

Edition

JAMA neurology, Chicago, IL, American Medical Association, 2021, 2168-6149

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30103 Neurosciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 29.907

RIV identification code

RIV/00216224:14110/21:00120826

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1001/jamaneurol.2020.3836

UT WoS

000587482800003

Keywords in English

Microbleeds; Anticoagulation; Embolic Stroke

Abstract

V originále

IMPORTANCE The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging. OBJECTIVE To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy. DESIGN, SETTING, AND PARTICIPANTS Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial. Participants were enrolled between December 2014 and September 2017 and followed up for a median of 11 months. The study setting included 459 stroke recruitment centers in 31 countries. Patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of these 7213 NAVIGATE ESUS participants, 3699 (51%) had information on cerebral microbleeds reported on their baseline clinical magnetic resonance imaging and were eligible for these analyses. Patients with a prior history of symptomatic intracerebral hemorrhage were excluded from the NAVIGATE ESUS trial. INTERVENTIONS Rivaroxaban, 15 mg, compared with aspirin, 100 mg, daily. MAIN OUTCOMES AND MEASURES The primary outcome was recurrent stroke. Secondary outcomes were ischemic stroke, intracerebral hemorrhage, and all-cause mortality. RESULTS Microbleeds were present in 395 of 3699 participants (11%). Of patients with cerebral microbleeds, mean (SD) age was 69.5 (9.4) years, 241 were men (61%), and 201 were White (51%). Advancing age (odds ratio [OR] per year, 1.03; 95% CI, 1.01-1.04), East Asian race/ethnicity (OR, 1.57; 95% CI, 1.04-2.37), hypertension (OR, 2.20; 95% CI, 1.54-3.15), multiterritorial infarcts (OR, 1.95; 95% CI, 1.42-2.67), chronic infarcts (OR, 1.78; 95% CI, 1.42-2.23), and occult intracerebral hemorrhage (OR, 5.23; 95% CI, 2.76-9.90) were independently associated with microbleeds. The presence of microbleeds was associated with a 1.5-fold increased risk of recurrent stroke (hazard ratio [HR], 1.5; 95% CI, 1.0-2.3), a 4-fold risk of intracerebral hemorrhage (HR, 4.2; 95% CI, 1.3-13.9), a 2-fold risk of all-cause mortality (HR, 2.1; 95% CI, 1.1-4.3), and strictly lobar microbleeds with an approximately 2.5-fold risk of ischemic stroke (HR, 2.3; 95% CI, 1.3-4.3). There were no interactions between microbleeds and treatment assignments for recurrent stroke, ischemic stroke, or all-cause mortality. The HR of intracerebral hemorrhage on rivaroxaban was similar between persons with microbleeds (HR, 3.1; 95% CI, 0.3-30.0) and persons without microbleeds (HR, 3.0; 95% CI, 0.6-14.7; interaction P > .99). CONCLUSIONS AND RELEVANCE Microbleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical outcomes.

Citovat

SHOAMANESH, A., R. G. HART, S. J. CONNOLLY, SE KASNER, E. E. SMITH, J. MARTI-FABREGAS, Y. Y. LIU, S. UCHIYAMA, Robert MIKULÍK, R. VELTKAMP, M. J. O DONNELL, G. NTAIOS, K. W. MUIR, T. S. FIELD, G. C. SANTO, V. OLAVARRIA, H. MUNDL, H. LUTSEP, S. D. BERKOWITZ and M. SHARMA. Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial. JAMA neurology. Chicago, IL: American Medical Association, 2021, vol. 78, No 1, p. 11-20. ISSN 2168-6149. Available from: https://dx.doi.org/10.1001/jamaneurol.2020.3836.

@article{1698776,
   author = {Shoamanesh, A. and Hart, R. G. and Connolly, S. J. and Kasner, SE and Smith, E. E. and MartiandFabregas, J. and Liu, Y. Y. and Uchiyama, S. and Mikulík, Robert and Veltkamp, R. and O Donnell, M. J. and Ntaios, G. and Muir, K. W. and Field, T. S. and Santo, G. C. and Olavarria, V. and Mundl, H. and Lutsep, H. and Berkowitz, S. D. and Sharma, M.},
   article_location = {Chicago, IL},
   article_number = {1},
   doi = {http://dx.doi.org/10.1001/jamaneurol.2020.3836},
   keywords = {Microbleeds; Anticoagulation; Embolic Stroke},
   language = {eng},
   issn = {2168-6149},
   journal = {JAMA neurology},
   title = {Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial},
   url = {https://jamanetwork.com/journals/jamaneurology/fullarticle/2771829},
   volume = {78},
   year = {2021}
}

TY  - JOUR
ID  - 1698776
AU  - Shoamanesh, A. - Hart, R. G. - Connolly, S. J. - Kasner, SE - Smith, E. E. - Marti-Fabregas, J. - Liu, Y. Y. - Uchiyama, S. - Mikulík, Robert - Veltkamp, R. - O Donnell, M. J. - Ntaios, G. - Muir, K. W. - Field, T. S. - Santo, G. C. - Olavarria, V. - Mundl, H. - Lutsep, H. - Berkowitz, S. D. - Sharma, M.
PY  - 2021
TI  - Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial
JF  - JAMA neurology
VL  - 78
IS  - 1
SP  - 11-20
EP  - 11-20
PB  - American Medical Association
SN  - 21686149
KW  - Microbleeds
KW  - Anticoagulation
KW  - Embolic Stroke
UR  - https://jamanetwork.com/journals/jamaneurology/fullarticle/2771829
L2  - https://jamanetwork.com/journals/jamaneurology/fullarticle/2771829
N2  - IMPORTANCE The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging. OBJECTIVE To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy. DESIGN, SETTING, AND PARTICIPANTS Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial. Participants were enrolled between December 2014 and September 2017 and followed up for a median of 11 months. The study setting included 459 stroke recruitment centers in 31 countries. Patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of these 7213 NAVIGATE ESUS participants, 3699 (51%) had information on cerebral microbleeds reported on their baseline clinical magnetic resonance imaging and were eligible for these analyses. Patients with a prior history of symptomatic intracerebral hemorrhage were excluded from the NAVIGATE ESUS trial. INTERVENTIONS Rivaroxaban, 15 mg, compared with aspirin, 100 mg, daily. MAIN OUTCOMES AND MEASURES The primary outcome was recurrent stroke. Secondary outcomes were ischemic stroke, intracerebral hemorrhage, and all-cause mortality. RESULTS Microbleeds were present in 395 of 3699 participants (11%). Of patients with cerebral microbleeds, mean (SD) age was 69.5 (9.4) years, 241 were men (61%), and 201 were White (51%). Advancing age (odds ratio [OR] per year, 1.03; 95% CI, 1.01-1.04), East Asian race/ethnicity (OR, 1.57; 95% CI, 1.04-2.37), hypertension (OR, 2.20; 95% CI, 1.54-3.15), multiterritorial infarcts (OR, 1.95; 95% CI, 1.42-2.67), chronic infarcts (OR, 1.78; 95% CI, 1.42-2.23), and occult intracerebral hemorrhage (OR, 5.23; 95% CI, 2.76-9.90) were independently associated with microbleeds. The presence of microbleeds was associated with a 1.5-fold increased risk of recurrent stroke (hazard ratio [HR], 1.5; 95% CI, 1.0-2.3), a 4-fold risk of intracerebral hemorrhage (HR, 4.2; 95% CI, 1.3-13.9), a 2-fold risk of all-cause mortality (HR, 2.1; 95% CI, 1.1-4.3), and strictly lobar microbleeds with an approximately 2.5-fold risk of ischemic stroke (HR, 2.3; 95% CI, 1.3-4.3). There were no interactions between microbleeds and treatment assignments for recurrent stroke, ischemic stroke, or all-cause mortality. The HR of intracerebral hemorrhage on rivaroxaban was similar between persons with microbleeds (HR, 3.1; 95% CI, 0.3-30.0) and persons without microbleeds (HR, 3.0; 95% CI, 0.6-14.7; interaction P > .99). CONCLUSIONS AND RELEVANCE Microbleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical outcomes.
ER  -

SHOAMANESH, A., R. G. HART, S. J. CONNOLLY, SE KASNER, E. E. SMITH, J. MARTI-FABREGAS, Y. Y. LIU, S. UCHIYAMA, Robert MIKULÍK, R. VELTKAMP, M. J. O DONNELL, G. NTAIOS, K. W. MUIR, T. S. FIELD, G. C. SANTO, V. OLAVARRIA, H. MUNDL, H. LUTSEP, S. D. BERKOWITZ and M. SHARMA. Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial. \textit{JAMA neurology}. Chicago, IL: American Medical Association, 2021, vol.~78, No~1, p.~11-20. ISSN~2168-6149. Available from: https://dx.doi.org/10.1001/jamaneurol.2020.3836.

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