Recurrent Stroke With Rivaroxaban Compared With Aspirin
According to Predictors of Atrial Fibrillation Secondary
Analysis of the NAVIGATE ESUS Randomized Clinical Trial

J 2019

Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial

HEALEY, J. S., D. J. GLADSTONE, B. SWAMINATHAN, J. ECKSTEIN, H. MUNDL et. al.

Basic information

Original name

Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial

Authors

HEALEY, J. S. (124 Canada, guarantor), D. J. GLADSTONE (124 Canada), B. SWAMINATHAN (124 Canada), J. ECKSTEIN (756 Switzerland), H. MUNDL (276 Germany), A. E. EPSTEIN (840 United States of America), K. G. HAEUSLER (276 Germany), Robert MIKULÍK (203 Czech Republic, belonging to the institution), S. E. KASNER (840 United States of America), D. TONI (380 Italy), A. ARAUZ (484 Mexico), G. NTAIOS (300 Greece), G. J. HANKEY (36 Australia), K. PERERA (124 Canada), J. PAGOLA (124 Canada), A. SHUAIB (124 Canada), H. LUTSEP (840 United States of America), X. M. YANG (156 China), S. UCHIYAMA (392 Japan), M. ENDRES (276 Germany), S. B. COUTTS (124 Canada), M. KARLINSKI (616 Poland), A. CZLONKOWSKA (616 Poland), C. A. MOLINA (724 Spain), G. SANTO (620 Portugal), S. D. BERKOWITZ (840 United States of America), R. G. HART (124 Canada) and S. J. CONNOLLY (124 Canada)

Edition

JAMA neurology, Chicago, IL, American Medical Association, 2019, 2168-6149

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30210 Clinical neurology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 13.608

RIV identification code

RIV/00216224:14110/19:00113269

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1001/jamaneurol.2019.0617

UT WoS

000483154300006

Keywords in English

ISCHEMIC-STROKE; CRYPTOGENIC STROKE; ORAL ANTICOAGULANTS; UNDETERMINED SOURCE; RISK; METAANALYSIS; RATIONALE; DESIGN; SCORE; SIZE

Abstract

V originále

IMPORTANCE The NAVIGATE ESUS randomized clinical trial found that 15 mg of rivaroxaban per day does not reduce stroke compared with aspirin in patients with embolic stroke of undetermined source (ESUS); however, it substantially reduces stroke risk in patients with atrial fibrillation (AF). OBJECTIVE To analyze whether rivaroxaban is associated with a reduction of recurrent stroke among patients with ESUS who have an increased risk of AF. DESIGN, SETTING, AND PARTICIPANTS Participants were stratified by predictors of AF, including left atrial diameter, frequency of premature atrial contractions, and HAVOC score, a validated scheme using clinical features. Treatment interactions with these predictors were assessed. Participants were enrolled between December 2014 and September 2017, and analysis began March 2018. INTERVENTION Rivaroxaban treatment vs aspirin. MAIN OUTCOMES AND MEASURES Risk of ischemic stroke. RESULTS Among 7112 patients with a mean (SD) age of 67 (9.8) years, the mean (SD) HAVOC score was 2.6(1.8), the mean (SD) left atrial diameter was 3.8(1.4) cm (n=4022), and the median (interquartile range) daily frequency of premature atrial contractions was 48 (13-222). Detection of AF during follow-up increased for each tertile of HAVOC score: 2.3% (score, 0-2), 3.0% (score, 3), and 5.8% (score, >3); however, neither tertiles of the HAVOC score nor premature atrial contractions frequency impacted the association of rivaroxaban with recurrent ischemic stroke (P for interaction=.67 and .96, respectively). Atrial fibrillation annual incidence increased for each tertile of left atrial diameter (2.0%, 3.6%, and 5.2%) and for each tertile of premature atrial contractions frequency (1.3%, 2.9%, and 7.0%). Among the predefined subgroup of patients with a left atrial diameter of more than 4.6 cm (9% of overall population), the risk of ischemic stroke was lower among the rivaroxaban group (1.7% per year) compared with the aspirin group (6.5% per year) (hazard ratio,0.26; 95% CI, 0.07-0.94; P for interaction=.02). CONCLUSIONS AND RELEVANCE The HAVOC score, left atrial diameter, and premature atrial contraction frequency predicted subsequent clinical AF. Rivaroxaban was associated with a reduced risk of recurrent stroke among patients with ESUS and moderate or severe left atrial enlargement; however, this needs to be independently confirmed before influencing clinical practice.

Citovat

HEALEY, J. S., D. J. GLADSTONE, B. SWAMINATHAN, J. ECKSTEIN, H. MUNDL, A. E. EPSTEIN, K. G. HAEUSLER, Robert MIKULÍK, S. E. KASNER, D. TONI, A. ARAUZ, G. NTAIOS, G. J. HANKEY, K. PERERA, J. PAGOLA, A. SHUAIB, H. LUTSEP, X. M. YANG, S. UCHIYAMA, M. ENDRES, S. B. COUTTS, M. KARLINSKI, A. CZLONKOWSKA, C. A. MOLINA, G. SANTO, S. D. BERKOWITZ, R. G. HART and S. J. CONNOLLY. Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial. JAMA neurology. Chicago, IL: American Medical Association, 2019, vol. 76, No 7, p. 764-773. ISSN 2168-6149. Available from: https://dx.doi.org/10.1001/jamaneurol.2019.0617.

@article{1636376,
   author = {Healey, J. S. and Gladstone, D. J. and Swaminathan, B. and Eckstein, J. and Mundl, H. and Epstein, A. E. and Haeusler, K. G. and Mikulík, Robert and Kasner, S. E. and Toni, D. and Arauz, A. and Ntaios, G. and Hankey, G. J. and Perera, K. and Pagola, J. and Shuaib, A. and Lutsep, H. and Yang, X. M. and Uchiyama, S. and Endres, M. and Coutts, S. B. and Karlinski, M. and Czlonkowska, A. and Molina, C. A. and Santo, G. and Berkowitz, S. D. and Hart, R. G. and Connolly, S. J.},
   article_location = {Chicago, IL},
   article_number = {7},
   doi = {http://dx.doi.org/10.1001/jamaneurol.2019.0617},
   keywords = {ISCHEMIC-STROKE; CRYPTOGENIC STROKE; ORAL ANTICOAGULANTS; UNDETERMINED SOURCE; RISK; METAANALYSIS; RATIONALE; DESIGN; SCORE; SIZE},
   language = {eng},
   issn = {2168-6149},
   journal = {JAMA neurology},
   title = {Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial},
   url = {http://dx.doi.org/10.1001/jamaneurol.2019.0617},
   volume = {76},
   year = {2019}
}

TY  - JOUR
ID  - 1636376
AU  - Healey, J. S. - Gladstone, D. J. - Swaminathan, B. - Eckstein, J. - Mundl, H. - Epstein, A. E. - Haeusler, K. G. - Mikulík, Robert - Kasner, S. E. - Toni, D. - Arauz, A. - Ntaios, G. - Hankey, G. J. - Perera, K. - Pagola, J. - Shuaib, A. - Lutsep, H. - Yang, X. M. - Uchiyama, S. - Endres, M. - Coutts, S. B. - Karlinski, M. - Czlonkowska, A. - Molina, C. A. - Santo, G. - Berkowitz, S. D. - Hart, R. G. - Connolly, S. J.
PY  - 2019
TI  - Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial
JF  - JAMA neurology
VL  - 76
IS  - 7
SP  - 764-773
EP  - 764-773
PB  - American Medical Association
SN  - 21686149
KW  - ISCHEMIC-STROKE
KW  - CRYPTOGENIC STROKE
KW  - ORAL ANTICOAGULANTS
KW  - UNDETERMINED SOURCE
KW  - RISK
KW  - METAANALYSIS
KW  - RATIONALE
KW  - DESIGN
KW  - SCORE
KW  - SIZE
UR  - http://dx.doi.org/10.1001/jamaneurol.2019.0617
L2  - http://dx.doi.org/10.1001/jamaneurol.2019.0617
N2  - IMPORTANCE The NAVIGATE ESUS randomized clinical trial found that 15 mg of rivaroxaban per day does not reduce stroke compared with aspirin in patients with embolic stroke of undetermined source (ESUS); however, it substantially reduces stroke risk in patients with atrial fibrillation (AF). OBJECTIVE To analyze whether rivaroxaban is associated with a reduction of recurrent stroke among patients with ESUS who have an increased risk of AF. DESIGN, SETTING, AND PARTICIPANTS Participants were stratified by predictors of AF, including left atrial diameter, frequency of premature atrial contractions, and HAVOC score, a validated scheme using clinical features. Treatment interactions with these predictors were assessed. Participants were enrolled between December 2014 and September 2017, and analysis began March 2018. INTERVENTION Rivaroxaban treatment vs aspirin. MAIN OUTCOMES AND MEASURES Risk of ischemic stroke. RESULTS Among 7112 patients with a mean (SD) age of 67 (9.8) years, the mean (SD) HAVOC score was 2.6(1.8), the mean (SD) left atrial diameter was 3.8(1.4) cm (n=4022), and the median (interquartile range) daily frequency of premature atrial contractions was 48 (13-222). Detection of AF during follow-up increased for each tertile of HAVOC score: 2.3% (score, 0-2), 3.0% (score, 3), and 5.8% (score, >3); however, neither tertiles of the HAVOC score nor premature atrial contractions frequency impacted the association of rivaroxaban with recurrent ischemic stroke (P for interaction=.67 and .96, respectively). Atrial fibrillation annual incidence increased for each tertile of left atrial diameter (2.0%, 3.6%, and 5.2%) and for each tertile of premature atrial contractions frequency (1.3%, 2.9%, and 7.0%). Among the predefined subgroup of patients with a left atrial diameter of more than 4.6 cm (9% of overall population), the risk of ischemic stroke was lower among the rivaroxaban group (1.7% per year) compared with the aspirin group (6.5% per year) (hazard ratio,0.26; 95% CI, 0.07-0.94; P for interaction=.02). CONCLUSIONS AND RELEVANCE The HAVOC score, left atrial diameter, and premature atrial contraction frequency predicted subsequent clinical AF. Rivaroxaban was associated with a reduced risk of recurrent stroke among patients with ESUS and moderate or severe left atrial enlargement; however, this needs to be independently confirmed before influencing clinical practice.
ER  -

HEALEY, J. S., D. J. GLADSTONE, B. SWAMINATHAN, J. ECKSTEIN, H. MUNDL, A. E. EPSTEIN, K. G. HAEUSLER, Robert MIKULÍK, S. E. KASNER, D. TONI, A. ARAUZ, G. NTAIOS, G. J. HANKEY, K. PERERA, J. PAGOLA, A. SHUAIB, H. LUTSEP, X. M. YANG, S. UCHIYAMA, M. ENDRES, S. B. COUTTS, M. KARLINSKI, A. CZLONKOWSKA, C. A. MOLINA, G. SANTO, S. D. BERKOWITZ, R. G. HART and S. J. CONNOLLY. Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial. \textit{JAMA neurology}. Chicago, IL: American Medical Association, 2019, vol.~76, No~7, p.~764-773. ISSN~2168-6149. Available from: https://dx.doi.org/10.1001/jamaneurol.2019.0617.

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