Chaturvedi Seemant
Department of Neurology and Stroke Program, Wayne State University, Detroit, Michigan 48201, USA.
Clin Ther. 2008 Jul;30(7):1196-205. doi: 10.1016/s0149-2918(08)80046-x.
Approximately 25% of strokes are recurrent. Antiplatelet therapy is indicated for the prevention of recurrent stroke in patients with a history of noncardioembolic minor stroke or transient ischemic attack (TIA). Although clinicians may choose acetylsalicylic acid (ASA) as first-line therapy for secondary prevention, clinical guidelines and evidence from trials suggest that ASA may not be the most effective strategy.
The purpose of this review was to discuss results from clinical trials that have compared the efficacy of ASA monotherapy versus ASA + extendedrelease dipyridamole in secondary stroke prevention.
Relevant randomized experimental and clinical studies in patients with a history of minor stroke or TIA of noncardioembolic etiology were identified using a search of the US National Library of Medicine database, with no limits on publication dates. The primary search terms used were secondary stroke prevention, antiplatelet therapy, acetylsalicylic acid, ASA, aspirin, aspirin + extended-release dipyridamole, and combination therapy.
Early trials of dipyridamole monotherapy or ASA + dipyridamole involved small numbers of patients and found no significant treatment differences. Two major trials that compared ASA monotherapy, dipyridamole monotherapy, and ASA + dipyridamole were identified: the Second European Stroke Prevention Study (ESPS-2) and the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT). Efficacy measurements in ESPS-2 found that stroke relative risk reductions were 18% (P = 0.013), 16% (P = 0.039), and 37% (P < 0.001), respectively, compared with placebo for a relative risk reduction of 23.1% (P = 0.006) favoring the combination over ASA monotherapy. In ESPRIT, patients who received ASA + dipyridamole had a 20% relative risk reduction versus ASA monotherapy for the composite end point of death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complications. In ESPS-2, headache was 5% more common with dual therapy compared with ASA monotherapy. ESPRIT found that combination treatment was not associated with a higher complication rate than ASA monotherapy, but that the rate of withdrawal due to adverse events was higher in the group that received the combination.
Based on the results from these 2 large, randomized trials, ASA + dipyridamole was more effective than ASA monotherapy as first-line therapy for secondary stroke prevention in these patients with a history of minor stroke or TIA of noncardioembolic etiology.
约25%的中风会复发。对于有非心源性轻度中风或短暂性脑缺血发作（TIA）病史的患者，抗血小板治疗可用于预防中风复发。尽管临床医生可能会选择乙酰水杨酸（ASA）作为二级预防的一线治疗方法，但临床指南和试验证据表明，ASA可能不是最有效的策略。
本综述的目的是讨论比较ASA单药治疗与ASA + 缓释双嘧达莫在二级中风预防中疗效的临床试验结果。
通过检索美国国立医学图书馆数据库，确定了有非心源性病因的轻度中风或TIA病史患者的相关随机实验和临床研究，对发表日期无限制。使用的主要检索词为二级中风预防、抗血小板治疗、乙酰水杨酸、ASA、阿司匹林、阿司匹林 + 缓释双嘧达莫和联合治疗。
双嘧达莫单药治疗或ASA + 双嘧达莫的早期试验纳入的患者数量较少，未发现显著的治疗差异。确定了两项比较ASA单药治疗、双嘧达莫单药治疗和ASA + 双嘧达莫的主要试验：第二次欧洲中风预防研究（ESPS - 2）和欧洲/澳大拉西亚可逆性缺血性中风预防试验（ESPRIT）。ESPS - 2中的疗效测量发现，与安慰剂相比，中风相对风险降低率分别为18%（P = 0.013）、16%（P = 0.039）和37%（P < 0.001），相对风险降低23.1%（P = 0.006），联合治疗优于ASA单药治疗。在ESPRIT中，接受ASA + 双嘧达莫治疗的患者与接受ASA单药治疗的患者相比，在所有血管原因导致的死亡、非致命性中风、非致命性心肌梗死或大出血并发症的复合终点方面，相对风险降低了20%。在ESPS - 2中，与ASA单药治疗相比，双联治疗的头痛发生率高5%。ESPRIT发现联合治疗与ASA单药治疗相比并发症发生率没有更高，但接受联合治疗的组因不良事件退出的发生率更高。
基于这两项大型随机试验的结果，对于有非心源性病因的轻度中风或TIA病史的患者，ASA + 双嘧达莫作为二级中风预防的一线治疗比ASA单药治疗更有效。
