Combined Analysis

Patients suffering from transient ischaemic attack (TIA) or ischaemic stroke have a high risk of suffering a first or recurrent stroke, with an annual risk of between 5 and 15%. The second European Stroke Prevention Study (ESPS 2) was a randomised, double-blind, placebo-controlled trial involving 6,602 patients with TIA or stroke comparing ASA alone (50 mg daily), modified-release (MR) dipyridamole alone (200 mg twice daily), ASA plus dipyridamole, and placebo. The 2-year relative risk reduction of stroke in the ASA plus MR-dipyridamole group (37.0%) was significantly higher than in either the ASA group (18.1%) or the MR-dipyridamole group (16.3%). The results of the comparison between ASA plus MR-dipyridamole versus placebo confirmed the findings of ESPS 1. The results of ESPS 2 were at odds with all prior trials with dipyridamole alone or in association with ASA, but it was also the only trial sufficiently powered to show a significant difference. For this reason, a meta-analysis was performed based on a systematic review of individual patient data from randomised controlled trials involving dipyridamole in patients with prior ischaemic stroke or TIA. Recurrent stroke was reduced by dipyridamole compared with placebo, and by combined ASA and dipyridamole versus ASA alone, dipyridamole alone or placebo. In two post hoc analyses the efficacy of ASA plus extended-release dipyridamole was compared with ASA alone for the prevention of recurrent stroke among high-risk groups. Stroke models from the Framingham Study and the Stroke Prognostic Instrument II were applied to subjects in ESPS 2 to assign patients to risk groups.