Modified-Release Dipyridamole Combined with Aspirin for Secondary Stroke Prevention

Patients suffering from transient ischemic attack (TIA) or ischemic stroke have a high risk of suffering a first or recurrent stroke, with an annual risk of between 5 and 15%. The European Stroke Prevention Study (ESPS)2 was a randomized, double-blind, placebo-controlled trial involving 6602 patients with TIA or stroke comparing aspirin alone (50 mg daily), modified-release (MR) dipyridamole alone (200 mg twice daily), aspirin plus dipyridamole, and placebo. The 2-year relative risk reduction of stroke in the aspirin plus MR-dipyridamole group (37.0%) was significantly higher than in either the aspirin group (18.1%) or the MR-dipyridamole group (16.3%). The results of the comparison between aspirin plus MR-dipyridamole versus placebo confirmed the findings of ESPS1. The results of ESPS2 were at odds with all prior trials with dipyridamole alone or in association with aspirin, 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 randomized controlled trials involving dipyridamole in patients with prior ischemic stroke or TIA. Recurrent stroke was reduced by dipyridamole compared with placebo, and by combined aspirin and dipyridamole versus aspirin alone, dipyridamole alone or placebo. In two post hoc analyses the efficacy of aspirin plus extended-release dipyridamole was compared with aspirin 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 ESPS2 to assign patients to risk groups. Compared with aspirin alone, aspirin plus MR-dipyridamole demonstrated a more pronounced efficacy in reducing the risk for stroke and vascular events among patients younger than 70 years of age, with hypertension, or prior stroke; current smokers; and those with any prior cardiovascular disease. Another model (Essen risk score) showed that patients with a high risk of recurrent stroke show a much greater benefit from aspirin plus MR-dipyridamole compared with aspirin monotherapy than patients with a low risk.