European stroke prevention study .2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke
European stroke prevention study .2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke
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DOI：
10.1016/s0022-510x(96)00308-5
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发表时间：
1996-11-01
影响因子：
4.4
通讯作者：
Lowenthal, A
中科院分区：
文献类型：
--
作者：
Diener, HC;Cunha, L;Lowenthal, A
1988年，我们进行了一项随机、安慰剂对照、双盲试验，以研究小剂量乙酰水杨酸(ASA)、改良释药双嘧达莫以及这两种药物联合用于缺血性卒中二级预防的安全性和有效性。既往有中风或短暂性脑缺血发作(TLA)史的患者被随机分成两组，分别接受单用ASA(每天50毫克)、单用改良型双嘧达莫(每日400 mg)或安慰剂治疗。主要终点是中风、死亡和中风或死亡。TIA和其他血管事件是次要终点。对患者进行为期两年的跟踪治疗。对6602名患者的数据进行了分析。析因分析显示，阿司匹林和潘生丁在降低卒中风险(P<0.001)和卒中或死亡风险方面有非常显著的效果(P<；0.01)。在成对比较中，与安慰剂相比，单独服用阿司匹林的中风风险降低了18%(p=0.013)；单独服用潘生丁的中风风险降低了16%(p=0.039)；联合治疗的中风风险降低了37%(p<；0.001)。单用阿司匹林治疗中风或死亡的风险降低13%(p=0.016)；单用潘生丁治疗中风或死亡的风险降低15%(p=0.015)；联合用药治疗中风或死亡的风险降低24%(p<；0.001)。单就死亡率而言，这种治疗并没有统计学上的显著影响。析因分析也显示阿司匹林(P<；0.001)和潘生丁(P<；0.01)对预防短暂性脑缺血发作有非常显著的效果。与安慰剂相比，联合用药的风险降低了36%(p<；0.001)。头痛是最常见的不良事件，在接受潘生丁治疗的患者中发生得更频繁。与安慰剂或潘生丁相比，接受ASA治疗的患者中，全部位出血和胃肠道出血的发生率明显更高。我们得出的结论是：(1)对于缺血性中风和短暂性脑缺血发作的二级预防，ASA25 mg每日两次和潘生丁改良释药，每天两次200毫克的剂量被证明是同样有效的；(2)当联合处方时，保护作用是相加的，联合明显比单独开药更有效，(3)小剂量ASA并不能消除诱发出血的倾向。
In 1988, we undertook a randomized, placebo-controlled, double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid (ASA), modified-release dipyridamole, and the two agents in combination for secondary prevention of ischemic stroke. Patients with prior stroke or transient ischemic attack (TLA) were randomized to treatment with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. Data from 6,602 patients were analysed. Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke (p less than or equal to 0.001) and stroke or death combined (p < 0.01). In pairwise comparisons, stroke risk in comparison to placebo was reduced by 18% with ASA alone (p = 0.013); 16% with dipyridamole alone (p = 0.039); and 37% with combination therapy (p < 0.001). Risk of stroke or death was reduced by 13% with ASA alone (p = 0.016); 15% with dipyridamole alone (p = 0.015); and 24% with the combination (p < 0.001). The treatment had no statistically significant effect on the death rate alone. Factorial analysis also demonstrated a highly significant effect of ASA (p < 0.001) and dipyridamole (p < 0.01) for preventing TIA. The risk reduction for the combination was 36% (p < 0.001) in comparison with placebo. Headache was the most common adverse event, occurring more frequently in dipyridamole-treated patients. All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole. We conclude that (1) ASA 25 mg twice daily and dipyridamole, in a modified-release form, at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA; (2) when co-prescribed the protective effects are additive, the combination being significantly more effective than either agent prescribed singly, (3) low-dose ASA does not eliminate the propensity for induced bleeding.