Meta-Analysis of Common Antiplatelet Regimens After TIA or Stroke
Network meta-analysis can provide estimates of treatment efficacy of multiple treatment regimens, even when direct comparisons are unavailable. We used network meta-analysis to compare commonly used antiplatelet regimens in the prevention of serious vascular events after transient ischaemic attack (TIA) or stroke. We performed direct meta-analyses of randomized, controlled trials evawluating antiplatelet agents after TIA or stroke. We chose the endpoint stroke, myocardial infarction, and vascular death. Network meta-analysis was then used to estimate the relative efficacy of the various antiplatelet regimens. Twenty-four trials involving 42688 TIA or stroke patients who suffered 6830 serious vascular events were included. In the network meta-analysis, all antiplatelet regimens (aspirin, aspirin plus dipyridamole, thienopyridines, and combination of aspirin and thienopyridines) were significantly more effective than placebo. The combination of aspirin and dipyridamole was more effective than thienopyridines (OR, 0.84; 95% CI, 0.73-0.97) and more effective than aspirin (OR, 0.78; 95% CI, 0.70-0.87). Our analysis suggests that the most powerful antiplatelet regimen in the prevention of serious vascular events after TIA or stroke is the combination of aspirin and dipyridamole. Network meta-analysis could be used to synthesize accumulating evidence from clinical trials in a broad range of vascular disorders.

Statistical techniques have been developed to establish the relative efficacies of different treatment strategies even when these treatments have not been directly compared. The so-called network meta-analysis' has been used to compare the efficacy of different antihypertensive classes and to identify which antihypertensive class was most closely associated with diabetes or which treatment strategy prevented stroke in patients with atrial fibrillation. In a study on acute myocardial infarction, such a combination of direct and indirect comparison methods provided similar results to the results of a direct comparison.

Different antiplatelet regimens have been tested in the secondary prevention after transient ischaemic attack (TIA) and ischaemic stroke. Direct comparisons have been performed of antiplatelet therapies with placebo and between some antiplatelet agents. However, randomized data comparing the relative effect of some antiplatelet regimens are currently lacking (e.g. aspirin and dipyridamole vs. thienopyridines alone or in combination with aspirin) or unethical in the case of placebo controlled trials. The number of direct comparisons increases rapidly when several treatment options are available. Indirect comparisons are of ten implicitly made in meta-analyses or in guidelines when multiple treatment options exist.

To illustrate the power of network meta-analysis, we used a combination of direct and indirect comparisons to estimate the relative odds of developing incident vascular events during long-term treatment with commonly used antiplatelet agents after TIA or ischaemic stroke. We were specifically interested whether the combination of aspirin and dipyridamole would be superior to thienopyridines. Both treatments are recommended after TIA or ischaemic stroke, but direct comparisons are currently lacking. The results from the Prevention Regimen For Effectively avoiding Second Strokes (PROFESS) trial, which compares aspirin and extended release of dipyridamole with clopidogrel, will provide an opportunity to determine whether the estimate derived from this indirect comparison is correct.