Secondary prevention of stroke: does dipyridamole add to aspirin?

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.