Journal article
Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation: Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial.
- Healey JS Division of Cardiology, Hamilton Health Sciences, Population Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
- Gladstone DJ Division of Neurology and Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre and Sunnybrook Research Institute, Toronto, Ontario, Canada.
- Swaminathan B Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.
- Eckstein J Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
- Mundl H Bayer AG, Wuppertal, Germany.
- Epstein AE Electrophysiology Section, Cardiovascular Division University of Pennsylvania, Cardiology Section, Philadelphia VA Medical Center, Philadelphia.
- Haeusler KG Department of Neurology, Universitätsklinikum Würzburg, Würzburg, Germany.
- Mikulik R International Clinical Research Center and Neurology Department, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.
- Kasner SE Department of Neurology, University of Pennsylvania, Philadelphia.
- Toni D Department of Human Neurosciences, "Sapienza" University of Rome, Rome, Italy.
- Arauz A Instituto Nacional de Neurologia y Neurocirugia, Mexico D.F., Mexico City, Mexico.
- Ntaios G Department of Medicine, University of Thesally, Larissa, Greece.
- Hankey GJ UWA Medical School, University of Western Australia, Sir Charles Gairdner Hospital, Perth, Australia.
- Perera K McMaster University/Population Health Research Institute, Department of Medicine (Neurology), Hamilton, Ontario, Canada.
- Pagola J Unitat d'Ictus, Servei de Neurologia, Hospital Universitari Vall d'Hebrón, Barcelona, Spain.
- Shuaib A Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
- Lutsep H Department of Neurology, OHSU, VA Portland Health Care System, Portland, Oregon.
- Yang X Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
- Uchiyama S International University of Health and Welfare, Sanno Hospital and Sanno Medical Center, Tokyo, Japan.
- Endres M Klinik für Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
- Coutts SB Department of Clinical Neurosciences, Radiology, and Community Health Sciences, University of Calgary, Foothills Medical Centre, Calgary, Alberta, Canada.
- Karlinski M Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
- Czlonkowska A 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
- Molina CA Department of Pharmacology, Medical University of Warsaw, Warsaw, Poland.
- Santo G Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
- Berkowitz SD Bayer US LLC, Pharmaceuticals Clinical Development Thrombosis, Whippany, New Jersey.
- Hart RG Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.
- Connolly SJ Division of Cardiology, Hamilton Health Sciences, Population Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
- 2019-04-09
Published in:
- JAMA neurology. - 2019
Aged
Aged, 80 and over
Aspirin
Atrial Fibrillation
Factor Xa Inhibitors
Female
Humans
Intracranial Embolism
Male
Middle Aged
Platelet Aggregation Inhibitors
Recurrence
Risk Factors
Rivaroxaban
Secondary Prevention
Stroke
Treatment Outcome
English
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.
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1001/jamaneurol.2019.0617
- PMID 30958508
- Persistent URL
- https://folia.unifr.ch/global/documents/51087
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