Lowenthal A, Buyse M
Algemeen Ziekenhuis Middelheim, Antwerp.
Acta Neurol Belg. 1994;94(1):24-34.
The purpose of this paper is to evaluate, in the light of all available evidence, the place of aspirin alone and of aspirin combined with dipyridamole in the secondary prevention of cerebrovascular accidents.
We performed a meta-analysis of all identified double blind, controlled, studies in secondary prevention of cerebrovascular accidents for the following categories: studies comparing aspirin with placebo; studies comparing aspirin plus dipyridamole with placebo; studies comparing aspirin plus dipyridamole with aspirin alone. An indirect comparison was carried out to compare the results obtained with aspirin alone and those obtained with aspirin combined with dipyridamole.
The meta-analysis of trials involving aspirin alone against placebo showed a risk reduction on strokes (17% reduction, p = 0.02), "important vascular events", i.e. a combination of vascular deaths, non-fatal strokes and non-fatal myocardial infarction (18% reduction, p = 0.003). Fatal vascular events (vascular deaths and fatal strokes) did not seem to be reduced at all. The overall mortality was reduced by 10%, but this reduction failed to reach statistical significance (p = 0.23). The meta-analysis of trials involving aspirin combined with dipyridamole showed more important risk reductions on every outcome whether fatal or not. Strokes were reduced by 42% (p < 0.001), fatal strokes by 43% (p = 0.02) and vascular deaths by 24% (p = 0.07, not significant). The overall mortality was reduced by 30% (p = 0.004). Direct comparisons of aspirin with aspirin plus dipyridamole did not indicate differences between the two treatment regimens. However the sample sizes involved in these comparisons were far too small to be informative. Indirect comparisons yielded statistically significant results in favour of the combination in terms of "important vascular events" (p = 0.007), all strokes (p = 0.007) and fatal strokes (p = 0.03). The results were also in favour of the combination but not statistically significant in terms of all deaths (p = 0.10) and vascular deaths (p = 0.08).
Aspirin used alone reduces secondary occurrence of vascular events in cerebrovascular patients. There is no evidence, however, of a reduction of fatal events (vascular deaths and fatal strokes). In contrast, aspirin in combination with dipyridamole reduces non-fatal as well as fatal events. These results as well as the indirect comparisons of the risk reductions suggest that the combination of aspirin with dipyridamole may be superior to aspirin alone; this hypothesis is presently tested in a large randomized trial.
本文旨在根据所有现有证据，评估单用阿司匹林以及阿司匹林与双嘧达莫联合使用在脑血管意外二级预防中的地位。
我们对所有已确定的关于脑血管意外二级预防的双盲对照研究进行了荟萃分析，研究类别如下：比较阿司匹林与安慰剂的研究；比较阿司匹林加双嘧达莫与安慰剂的研究；比较阿司匹林加双嘧达莫与单用阿司匹林的研究。进行了间接比较，以对比单用阿司匹林和阿司匹林与双嘧达莫联合使用所获得的结果。
对涉及单用阿司匹林与安慰剂对照的试验进行荟萃分析显示，中风风险降低（降低17%，p = 0.02），“重要血管事件”，即血管性死亡、非致命性中风和非致命性心肌梗死的综合发生率降低（降低18%，p = 0.003）。致命性血管事件（血管性死亡和致命性中风）似乎并未降低。总死亡率降低了10%，但这一降低未达到统计学显著性（p = 0.23）。对涉及阿司匹林与双嘧达莫联合使用的试验进行荟萃分析显示，无论是否为致命性结局，各项风险降低更为显著。中风降低了42%（p < 0.001），致命性中风降低了43%（p = 0.02），血管性死亡降低了24%（p = 0.07，无显著性）。总死亡率降低了30%（p = 0.004）。阿司匹林与阿司匹林加双嘧达莫的直接比较未显示两种治疗方案之间存在差异。然而，这些比较中涉及的样本量过小，无法提供有用信息。间接比较在“重要血管事件”（p = 0.007）、所有中风（p = 0.007）和致命性中风（p = 0.03）方面得出了有利于联合用药的具有统计学显著性的结果。在所有死亡（p = 0.10）和血管性死亡（p = 0.08）方面，结果也有利于联合用药，但无统计学显著性。
单用阿司匹林可降低脑血管病患者血管事件的二次发生。然而，没有证据表明致命性事件（血管性死亡和致命性中风）有所减少。相比之下，阿司匹林与双嘧达莫联合使用可降低非致命性和致命性事件。这些结果以及风险降低的间接比较表明，阿司匹林与双嘧达莫联合使用可能优于单用阿司匹林；这一假设目前正在一项大型随机试验中进行检验。
