Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA

被引:946
作者
Johnston, S. Claiborne [1 ]
Easton, J. Donald [2 ]
Farrant, Mary [2 ]
Barsan, William [3 ]
Conwit, Robin A. [4 ]
Elm, Jordan J. [6 ]
Kim, Anthony S. [2 ]
Lindblad, Anne S. [5 ]
Palesch, Yuko Y. [6 ]
机构
[1] Univ Texas Austin, Dell Med Sch, Deans Off, Austin, TX 78701 USA
[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA
[3] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA
[4] NINDS, Div Clin Res, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA
[5] Emmes, Rockville, MD USA
[6] Univ South Carolina, Data Coordinat Unit, Dept Publ Hlth Sci, Charleston, SC USA
关键词
MINOR STROKE; ATTACK; EFFICACY; TICAGRELOR; SAFETY; TRIAL;
D O I
10.1056/NEJMoa1800410
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Combination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke or transient ischemic attack (TIA). A trial of combination antiplatelet therapy in a Chinese population has shown a reduction in the risk of recurrent stroke. We tested this combination in an international population. METHODS In a randomized trial, we assigned patients with minor ischemic stroke or high-risk TIA to receive either clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day) or the same range of doses of aspirin alone. The dose of aspirin in each group was selected by the site investigator. The primary efficacy outcome in a time-to-event analysis was the risk of a composite of major ischemic events, which was defined as ischemic stroke, myocardial infarction, or death from an ischemic vascular event, at 90 days. RESULTS A total of 4881 patients were enrolled at 269 international sites. The trial was halted after 84% of the anticipated number of patients had been enrolled because the data and safety monitoring board had determined that the combination of clopidogrel and aspirin was associated with both a lower risk of major ischemic events and a higher risk of major hemorrhage than aspirin alone at 90 days. Major ischemic events occurred in 121 of 2432 patients (5.0%) receiving clopidogrel plus aspirin and in 160 of 2449 patients (6.5%) receiving aspirin plus placebo (hazard ratio, 0.75; 95% confidence interval (CI], 0.59 to 0.95; P=0.02), with most events occurring during the first week after the initial event. Major hemorrhage occurred in 23 patients (0.996) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P=0.02). CONCLUSIONS In patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone.
引用
收藏
页码:215 / 225
页数:11
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