Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 764-773 |
| Number of pages | 10 |
| Journal | JAMA Neurology |
| Volume | 76 |
| Issue number | 7 |
| Early online date | 8 Apr 2019 |
| DOIs | |
| Publication status | Published - Jul 2019 |
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Recurrent stroke with rivaroxaban compared with aspirin according to predictors of atrial fibrillation : Secondary analysis of the NAVIGATE ESUS randomized clinical trial. / Healey, Jeff S; Gladstone, David J; Swaminathan, Balakumar; Eckstein, Jens; Mundl, Hardi; Epstein, Andrew E; Haeusler, Karl Georg; Mikulik, Robert; Kasner, Scott E; Toni, Danilo; Arauz, Antonio; Ntaios, George; Perera, Kanjana; Hankey, Graeme J; Pagola, Jorge; Shuaib, Ashfaq; Lutsep, Helmi; Yang, Xiaomeng; Uchiyama, Shinichiro; Endres, Matthias; Coutts, Shelagh B; Karlinski, Michal; Czlonkowska, Anna; Molina, Carlos A; Santo, Gustavo; Berkowitz, Scott D; Hart, Robert G; Connolly, Stuart J.
In: JAMA Neurology, Vol. 76, No. 7, 07.2019, p. 764-773.Research output: Contribution to journal › Article
TY - JOUR
T1 - Recurrent stroke with rivaroxaban compared with aspirin according to predictors of atrial fibrillation
T2 - Secondary analysis of the NAVIGATE ESUS randomized clinical trial
AU - Healey, Jeff S
AU - Gladstone, David J
AU - Swaminathan, Balakumar
AU - Eckstein, Jens
AU - Mundl, Hardi
AU - Epstein, Andrew E
AU - Haeusler, Karl Georg
AU - Mikulik, Robert
AU - Kasner, Scott E
AU - Toni, Danilo
AU - Arauz, Antonio
AU - Ntaios, George
AU - Perera, Kanjana
AU - Hankey, Graeme J
AU - Pagola, Jorge
AU - Shuaib, Ashfaq
AU - Lutsep, Helmi
AU - Yang, Xiaomeng
AU - Uchiyama, Shinichiro
AU - Endres, Matthias
AU - Coutts, Shelagh B
AU - Karlinski, Michal
AU - Czlonkowska, Anna
AU - Molina, Carlos A
AU - Santo, Gustavo
AU - Berkowitz, Scott D
AU - Hart, Robert G
AU - Connolly, Stuart J
PY - 2019/7
Y1 - 2019/7
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.
AB - 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.
KW - ISCHEMIC-STROKE
KW - CRYPTOGENIC STROKE
KW - ORAL ANTICOAGULANTS
KW - UNDETERMINED SOURCE
KW - RISK
KW - METAANALYSIS
KW - RATIONALE
KW - DESIGN
KW - SCORE
KW - SIZE
U2 - 10.1001/jamaneurol.2019.0617
DO - 10.1001/jamaneurol.2019.0617
M3 - Article
VL - 76
SP - 764
EP - 773
JO - Archives of neurology
JF - Archives of neurology
SN - 0003-9942
IS - 7
ER -