Aspirin and ticlopidine for prevention of recurrent stroke in black patients - A randomized trial
Aspirin and ticlopidine for prevention of recurrent stroke in black patients - A randomized trial
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DOI：
10.1001/jama.289.22.2947
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发表时间：
2003-06-11
影响因子：
120.7
通讯作者：
Leurgans, S
中科院分区：
文献类型：
--
作者：
Gorelick, PB;Richardson, D;Leurgans, S
黑人受中风的影响不成比例，他们死于中风或经历中风的可能性是美国其他大多数人的两倍。目的探讨阿司匹林和噻氯匹定预防黑人脑卒中复发的有效性和安全性。设计、环境和患者：随机、双盲、研究者发起的多中心试验，从1992年12月至2001年10月从美国62家学术和社区医院招募了1809名最近发生非心源性缺血性中风的黑人男性和女性，随访长达2年。902例患者接受噻氯匹定500 mg/d治疗，907例接受阿司匹林650 mg/d治疗。复发性卒中、心肌梗死或血管性死亡是复合主要终点（根据意向治疗分析）。次要结局是致死性或非致死性中风。研究的盲法阶段在大约6.5年后停止，因为无效分析显示噻氯匹定在预防主要结局终点方面优于阿司匹林的概率小于1%。902例噻氯匹定组患者中133例（14.7%）达到复发性卒中、心肌梗死或血管性死亡的主要结局，907例阿司匹林组患者中112例（12.3%）达到复发性卒中、心肌梗死或血管性死亡（风险比为1.22；95%可信区间为0.94-1.57）。Kaplan-Meier曲线对主要结局的事件时间没有显著差异（经log-rank检验P= 0.12）。致死性或非致死性卒中的次要结局的时间Kaplan-Meier曲线接近统计学上显著的降低，阿司匹林优于噻氯匹定（log-rank检验P= 0.08）。实验室确定的严重中性粒细胞减少的频率，噻氯匹定组为3.4%，阿司匹林组为2.2% (P= 0.12)，血小板减少组为0.3%，血小板减少组为0.2% （P= 0.69）。1例替氯匹定治疗的患者出现血小板减少症，被认为可能是血栓性血小板减少性紫癜，经血浆置换治疗后恢复。在为期2年的随访中，我们发现噻氯匹定和阿司匹林在预防卒中复发、心肌梗死或血管性死亡方面没有统计学上的显著差异。然而，在服用阿司匹林的人群中，致命性或非致命性中风的减少趋势并不显著。基于这些数据和噻氯匹定严重不良事件的风险，我们认为阿司匹林是一种更好的治疗阿司匹林耐受黑人非心脏栓塞性缺血性卒中的方法。
Context Blacks are disproportionately affected by stroke, and they are about 2 times more likely than most other individuals in the United States to die of or experience stroke.Objective To determine the efficacy and safety of aspirin and ticlopidine to prevent recurrent stroke in black patients.Design, Setting, and Patients Randomized, double-blind, investigator-initiated, multicenter trial of 1809 black men and women who recently had a noncardioembolic ischemic stroke and who were recruited between December 1992 and October 2001 from 62 academic and community hospitals in the United States and followed up for up to 2 years.Intervention A total of 902 patients received 500 mg/d of ticlopidine and 907 received 650 mg/d of aspirin.Main Outcome Measures Recurrent stroke, myocardial infarction, or vascular death was the composite primary end point (according to intention-to-treat analysis). The secondary outcome was fatal or nonfatal stroke.Results The blinded phase of the study was halted after about 6.5 years when futility analyses revealed a less than 1% probability of ticlopidine being shown superior to aspirin in the prevention of the primary outcome end point. The primary outcome of recurrent stroke, myocardial infarction, or vascular death was reached by 133 (14.7%) of 902 patients assigned to ticlopidine and 112 (12.3%) of 907 patients assigned to aspirin (hazard ratio, 1.22; 95% confidence interval, 0.94-1.57). Kaplan-Meier curves for time to event for the primary outcome did not differ significantly (P=.12 by log-rank test). Kaplan-Meier curves for time to the secondary outcome of fatal or nonfatal stroke approached a statistically significant reduction favoring aspirin over ticlopidine (P=.08 by log-rank test). The frequency of laboratory-determined serious neutropenia was 3.4% for patients receiving ticlopidine vs 2.2% for patients receiving aspirin (P=.12) and 0.3% vs 0.2% for thrombocytopenia, respectively (P=.69). One ticlopidine-treated patient developed thrombocytopenia, which was thought to be a case of possible thrombotic thrombocytopenia purpura, and recovered after therapy with plasmapheresis.Conclusions During a 2-year follow-up, we found no statistically significant difference between ticlopidine and aspirin in the prevention of recurrent stroke, myocardial infarction, or vascular death. However, there was a nonsignificant trend for reduction of fatal or nonfatal stroke among those in the aspirin group. Based on these data and the risk of serious adverse events with ticlopidine, we regard aspirin as a better treatment for aspirin-tolerant black patients with noncardioembolic ischemic stroke.