Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

被引：674

作者：

Sacco, Ralph L. ^{[1
]}

Diener, Hans-Christoph ^{[2
]}

Yusuf, Salim ^{[4
,5
]}

Cotton, Daniel ^{[8
]}

Ounpuu, Stephanie ^{[6
]}

Lawton, William A. ^{[9
]}

Palesch, Yuko ^{[11
]}

Martin, Renee H. ^{[11
]}

Albers, Gregory W. ^{[12
]}

Bath, Philip ^{[10
]}

Bornstein, Natan ^{[13
]}

Chan, Bernard P. L. ^{[14
]}

Chen, Sien-Tsong ^{[15
]}

Cunha, Luis ^{[16
]}

Dahlof, Bjorn ^{[17
]}

De Keyser, Jacques ^{[18
]}

Donnan, Geoffrey A. ^{[19
]}

Estol, Conrado ^{[20
]}

Gorelick, Philip ^{[21
]}

Gu, Vivian ^{[22
]}

Hermansson, Karin ^{[24
]}

Hilbrich, Lutz ^{[8
]}

Kaste, Markku ^{[25
]}

Lu, Chuanzhen ^{[23
]}

Machnig, Thomas ^{[3
]}

Pais, Prem ^{[26
]}

Roberts, Robin ^{[4
]}

Skvortsova, Veronika ^{[27
]}

Teal, Philip ^{[7
]}

Toni, Danilo ^{[28
]}

VanderMaelen, Cam ^{[8
]}

Voigt, Thor ^{[8
]}

Weber, Michael ^{[29
]}

Yoon, Byung-Woo ^{[30
]}

机构：

[1] Univ Miami, Miller Sch Med, Miami, FL 33136 USA

[2] Univ Duisberg Essen, Essen, Germany

[3] Boehringer Ingelheim KG, D-6507 Ingelheim, Germany

[4] McMaster Univ, Hamilton, ON, Canada

[5] Hamilton Hlth Sci, Hamilton, ON, Canada

[6] Boehringer Ingelheim GmbH & Co KG, Burlington, ON, Canada

[7] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada

[8] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA

[9] Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England

[10] Univ Nottingham, Nottingham NG7 2RD, England

[11] Med Univ S Carolina, Charleston, SC 29425 USA

[12] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA

[13] Ichilov Hosp, Tel Aviv, Israel

[14] Natl Univ Singapore Hosp, Singapore 117548, Singapore

[15] Chang Gung Mem Hosp, Taipei 10591, Taiwan

[16] Hosp Univ Coimbra, Coimbra, Portugal

[17] Sahlgrens Univ Hosp, Gothenburg, Sweden

[18] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands

[19] Univ Melbourne, Heidelberg West, Australia

[20] Neurol Ctr Treatment & Res, Buenos Aires, DF, Argentina

[21] Univ Illinois, Chicago, IL USA

[22] Boehringer Ingelheim Shanghai Pharmaceut, Shanghai, Peoples R China

[23] Huashan Hosp, Shanghai, Peoples R China

[24] Boehringer Ingelheim GmbH & Co KG, Stockholm, Sweden

[25] Univ Helsinki, Cent Hosp, Helsinki, Finland

[26] St Johns Med Coll, Bangalore, Karnataka, India

[27] Russian State Med Univ, Moscow 117437, Russia

[28] Univ Roma La Sapienza, Rome, Italy

[29] SUNY Downstate Coll Med, New York, NY USA

[30] Seoul Natl Univ Hosp, Seoul 110744, South Korea

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2008年 / 359卷 / 12期

关键词：

D O I：

10.1056/NEJMoa0805002

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens - aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. Methods: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. Results: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). Conclusions: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.).

引用

页码：1238 / 1251

页数：14