Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation: Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial
Language English Country United States Media print
Document type Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
30958508
PubMed Central
PMC6583060
DOI
10.1001/jamaneurol.2019.0617
PII: 2729692
Knihovny.cz E-resources
- MeSH
- Aspirin therapeutic use MeSH
- Stroke drug therapy MeSH
- Atrial Fibrillation MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Factor Xa Inhibitors therapeutic use MeSH
- Intracranial Embolism drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Recurrence MeSH
- Rivaroxaban therapeutic use MeSH
- Risk Factors MeSH
- Secondary Prevention MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Names of Substances
- Aspirin MeSH
- Platelet Aggregation Inhibitors MeSH
- Factor Xa Inhibitors MeSH
- Rivaroxaban MeSH
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.
2nd Department of Neurology Institute of Psychiatry and Neurology Warsaw Poland
Bayer US LLC Pharmaceuticals Clinical Development Thrombosis Whippany New Jersey
Beijing Tiantan Hospital Capital Medical University Beijing China
Department of Human Neurosciences Sapienza University of Rome Rome Italy
Department of Internal Medicine University Hospital Basel Basel Switzerland
Department of Medicine University of Alberta Edmonton Alberta Canada
Department of Medicine University of Thesally Larissa Greece
Department of Medicine University of Toronto Toronto Ontario Canada
Department of Neurology Institute of Psychiatry and Neurology Warsaw Poland
Department of Neurology OHSU VA Portland Health Care System Portland Oregon
Department of Neurology Universitätsklinikum Würzburg Würzburg Germany
Department of Neurology University of Pennsylvania Philadelphia
Department of Pharmacology Medical University of Warsaw Warsaw Poland
Instituto Nacional de Neurologia y Neurocirugia Mexico D F Mexico City Mexico
International University of Health and Welfare Sanno Hospital and Sanno Medical Center Tokyo Japan
Klinik für Neurologie Charité Universitätsmedizin Berlin Berlin Germany
Neurology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
Population Health Research Institute Hamilton Health Sciences Hamilton Ontario Canada
Unitat d'Ictus Servei de Neurologia Hospital Universitari Vall d'Hebrón Barcelona Spain
UWA Medical School University of Western Australia Sir Charles Gairdner Hospital Perth Australia
Vall d'Hebron Stroke Unit Hospital Universitari Vall d'Hebron Barcelona Spain
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