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

被引：172

作者：

Healey, Jeff S. ^{[1
]}

Gladstone, David J. ^{[2
,3
,4
]}

Swaminathan, Balakumar ^{[5
]}

Eckstein, Jens ^{[6
]}

Mundl, Hardi ^{[7
]}

Epstein, Andrew E. ^{[8
]}

Haeusler, Karl Georg ^{[9
]}

Mikulik, Robert ^{[10
,30
]}

Kasner, Scott E. ^{[10
,11
]}

Toni, Danilo ^{[12
]}

Arauz, Antonio ^{[13
]}

Ntaios, George ^{[14
]}

Hankey, Graeme J. ^{[15
]}

Perera, Kanjana ^{[16
]}

Pagola, Jorge ^{[31
]}

Shuaib, Ashfaq ^{[17
]}

Lutsep, Helmi ^{[18
]}

Yang, Xiaomeng ^{[19
]}

Uchiyama, Shinichiro ^{[20
]}

Endres, Matthias ^{[21
]}

Coutts, Shelagh B. ^{[22
]}

Karlinski, Michal ^{[23
]}

Czlonkowska, Anna ^{[24
,25
]}

Molina, Carlos A. ^{[25
,26
]}

Santo, Gustavo ^{[27
,28
]}

Berkowitz, Scott D. ^{[29
]}

Hart, Robert G. ^{[5
]}

Connolly, Stuart J. ^{[1
]}

机构：

[1] McMaster Univ, Dept Med, Populat Hlth Res Inst, Div Cardiol,Hamilton Hlth Sci, Hamilton, ON, Canada

[2] Sunnybrook Hlth Sci Ctr, Div Neurol & Hurvitz Brain Sci Program, Toronto, ON, Canada

[3] Sunnybrook Res Inst, Toronto, ON, Canada

[4] Univ Toronto, Dept Med, Toronto, ON, Canada

[5] Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada

[6] Univ Hosp Basel, Dept Internal Med, Basel, Switzerland

[7] Bayer AG, Wuppertal, Germany

[8] Univ Penn, Electrophysiol Sect, Cardiovasc Div, Cardiol Sect, Philadelphia, PA 19104 USA

[9] Univ Klinikum Wurzburg, Dept Neurol, Wurzburg, Germany

[10] St Annes Univ Hosp, Int Clin Res Ctr, Neurol Dept, Brno, Czech Republic

[11] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

[12] Sapienza Univ Rome, Dept Human Neurosci, Rome, Italy

[13] Inst Nacl Neurol Neurocirug, Mexico City, DF, Mexico

[14] Univ Thesally, Dept Med, Larisa, Greece

[15] Univ Western Australia, Sir Charles Gairdner Hosp, UWA Med Sch, Perth, WA, Australia

[16] McMaster Univ, Populat Hlth Res Inst, Dept Med Neurol, Hamilton, ON, Canada

[17] Univ Alberta, Dept Med, Edmonton, AB, Canada

[18] VA Portland Hlth Care Syst, OHSU, Dept Neurol, Portland, OR USA

[19] Capital Med Univ, Beijing Tiantan Hosp, Beijing, Peoples R China

[20] Int Univ Hlth & Welf, Sanno Hosp & Sanno Med Ctr, Tokyo, Japan

[21] Charite Univ Med Berlin, Klin Neurol, Berlin, Germany

[22] Univ Calgary, Dept Clin Neurosci Radiol & Community Hlth Sci, Foothills Med Ctr, Calgary, AB, Canada

[23] Inst Psychiat & Neurol, Dept Neurol, Warsaw, Poland

[24] Inst Psychiatiy & Neurol, Dept Neurol 2, Warsaw, Poland

[25] Med Univ Warsaw, Dept Pharmacol, Warsaw, Poland

[26] Hosp Univ Vail dHebron, Vail dHebron Stroke Unit, Barcelona, Spain

[27] Ctr Hosp, Neurol Dept, Coimbra, Portugal

[28] Univ Coimbra, Coimbra, Portugal

[29] Bayer US LLC, Pharmaceut Clin Dev Thrombosis, Whippany, NJ USA

[30] Masaryk Univ, Int Clin Res Ctr, Brno, Czech Republic

[31] Hosp Univ Vall Hebron, Servei Neurol, Unitat Ictus, Barcelona, Spain

来源：

JAMA NEUROLOGY | 2019年 / 76卷 / 07期

关键词：

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

D O I：

10.1001/jamaneurol.2019.0617

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：764 / 773

页数：10

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