Secondary stroke prevention: misguided by guidelines?

Despite large clinical trials, there is no consensus about the best antithrombotic strategy for the secondary prevention of non-cardioembolic ischaemic stroke.This retrospective study is the first to combine the results of the most important trials and to integrate data on study validity, effectiveness, adverse events, risk of non-compliance, and cost. We searched MEDLINE, EMBASE, and the Cochrane Database (1996 to July 2011) and selected long-term secondary prevention trials with treatment with aspirin, dipyridamole, clopidogrel, aspirin plus dipyridamole, or aspirin plus clopidogrel. Subgroup analyses were included to explain differences in interpretations that could have led to the differences in guidelines. Two trials showed a small but significant reduction with aspirin plus dipyridamole compared to aspirin (ARR 1.5%, P < 0.05 and ARR 1.0%, P < 0.05). There was no effect on vascular death. One trial showed a small but statistical significant reduction with clopidogrel compared to aspirin (ARR 0.5%, P < 0.05). The association of clopidogrel with aspirin could not show any significant benefit compared to clopidogrel monotherapy, nor compared to aspirin monotherapy, but showed higher rates of adverse events. Significantly more patients discontinued treatment with aspirin plus dipyridamole compared to aspirin monotherapy (34.5% versus 13.4% and 29.0% versus 22.2%, P < 0.001) and clopidogrel monotherapy (29.1% versus 22.6%, P < 0.001). Transposition of statistical significant reductions in stroke recurrence into clinical significance could not be supported. Despite changes in international guidelines, aspirin monotherapy should retain its position as the main antiplatelet agent for secondary prevention of non-cardioembolic ischaemic stroke.