Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source

被引：683

作者：

Hart, R. G. ^{[1
]}

Sharma, M. ^{[1
]}

Mundl, H. ^{[9
]}

Kasner, S. E. ^{[13
]}

Bangdiwala, S. I. ^{[2
]}

Berkowitz, S. D. ^{[15
]}

Swaminathan, B. ^{[5
]}

Lavados, P. ^{[16
]}

Wang, Y. ^{[17
,18
]}

Davalos, A. ^{[19
]}

Shamalov, N. ^{[20
]}

Mikulik, R. ^{[21
,22
]}

Cunha, L. ^{[23
]}

Lindgren, A. ^{[24
,25
]}

Arauz, A. ^{[27
]}

Lang, W. ^{[28
]}

Czlonkowska, A. ^{[29
,30
]}

Eckstein, J. ^{[31
]}

Gagliardi, R. J. ^{[32
]}

Amarenco, P. ^{[33
]}

Ameriso, S. F. ^{[34
]}

Tatlisumak, T. ^{[26
,35
]}

Veltkamp, R. ^{[36
]}

Hankey, G. J. ^{[37
,38
]}

Toni, D. ^{[39
]}

Bereczki, D. ^{[40
]}

Uchiyama, S. ^{[41
,42
]}

Ntaios, G. ^{[43
]}

Yoon, B. -W. ^{[44
]}

Brouns, R. ^{[45
,46
]}

Endres, M. ^{[10
]}

Muir, K. W. ^{[47
]}

Bornstein, N. ^{[48
]}

Ozturk, S. ^{[49
]}

O'Donnell, M. J. ^{[50
]}

Basson, M. M. De Vries ^{[51
]}

Pare, G. ^{[3
]}

Pater, C. ^{[12
]}

Kirsch, B. ^{[11
]}

Sheridan, P. ^{[5
]}

Peters, G. ^{[14
]}

Weitz, J. I. ^{[6
]}

Peacock, W. F. ^{[52
]}

Shoamanesh, A. ^{[1
]}

Benavente, O. R. ^{[7
]}

Joyner, C. ^{[8
]}

Themeles, E. ^{[5
]}

Connolly, S. J. ^{[4
]}

机构：

[1] Thrombosis & Atherosclerosis Res Inst, Dept Med Neurol, Hamilton, ON, Canada

[2] Thrombosis & Atherosclerosis Res Inst, Dept Hlth Res Methods Evidence & Impact, Hamilton, ON, Canada

[3] Thrombosis & Atherosclerosis Res Inst, Dept Pathol & Mol Med, Hamilton, ON, Canada

[4] Thrombosis & Atherosclerosis Res Inst, Dept Med Cardiol, Hamilton, ON, Canada

[5] Thrombosis & Atherosclerosis Res Inst, Populat Hlth Res Inst, Hamilton, ON, Canada

[6] McMaster Univ, Hamilton, ON, Canada

[7] Univ British Columbia, Vancouver Stroke Program, Vancouver, BC, Canada

[8] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada

[9] Bayer, Wuppertal, Germany

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

[11] Bayer, Berlin, Germany

[12] Bayer, Leverkusen, Germany

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

[14] Janssen Res & Dev, Spring House, PA USA

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

[16] Clin Alemana Santiago, Santiago, Chile

[17] Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China

[18] Beijing Tiantan Hosp, Stroke Ctr, Beijing, Peoples R China

[19] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Barcelona, Spain

[20] Pirogov Russian Natl Res Med Univ, Moscow, Russia

[21] St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic

[22] St Annes Univ Hosp, Neurol Dept, Brno, Czech Republic

[23] Hosp Univ Coimbra, Ctr Hosp & Univ Coimbra, Coimbra, Portugal

[24] Lund Univ, Dept Clin Sci Neurol, Lund, Sweden

[25] Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden

[26] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci Neurol, Gothenburg, Sweden

[27] Inst Nacl Neurol & Neurocirug, Mexico City, DF, Mexico

[28] Sigmund Freud Private Univ, Hosp St John God, Med Fac, Vienna, Austria

[29] Med Univ Warsaw, Inst Psychiat & Neurol, Dept Neurol 2, Warsaw, Poland

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

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

[32] Irmandade Santa Casa Misericordia Sao Paulo, Sao Paulo, Brazil

[33] Sorbonne Paris Cite Univ, Paris Diderot, Bichat Hosp, AP HP, Paris, France

[34] Fdn Lucha Enfermedades Neurol Infancia, Inst Neurol Research, Buenos Aires, DF, Argentina

[35] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland

[36] Imperial Coll London, London, England

[37] Univ Western Australia, Med Sch, Perth, WA, Australia

[38] Sir Charles Gairdner Hosp, Perth, WA, Australia

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

[40] Semmelweis Univ, Dept Neurol, Budapest, Hungary

[41] Int Univ Hlth & Welf, Sanno Hosp, Tokyo, Japan

[42] Sanno Med Ctr, Tokyo, Japan

[43] Univ Thessaly, Dept Med, Larisa, Greece

[44] Seoul Natl Univ Hosp, Seoul Natl Univ, Coll Med, Seoul, South Korea

[45] Vrije Univ Brussel, Fac Med & Pharm, Brussels, Belgium

[46] ZorgSaam Hosp, Dept Neurol, Terneuzen, Netherlands

[47] Queen Elizabeth Univ Hosp, Univ Glasgow, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland

[48] Shaare Zedek Med Ctr, Jerusalem, Israel

[49] Selcuk Univ, Dept Neurol, Konya, Turkey

[50] Natl Univ Ireland, Hlth Res Board Clin Res Facil, Galway, Ireland

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2018年 / 378卷 / 23期

关键词：

FORAMEN OVALE CLOSURE; ATRIAL-FIBRILLATION; CRYPTOGENIC STROKE; ANTITHROMBOTIC THERAPY; METAANALYSIS; EFFICACY; WARFARIN; TRIALS; DESIGN; SAFETY;

D O I：

10.1056/NEJMoa1802686

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). CONCLUSIONS Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding.

引用

页码：2191 / 2201

页数：11

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