Abstract
This systematic review evaluated the comparative effectiveness of aspirin plus extended-release dipyridamole (Asp+Dp) versus clopidogrel in preventing recurrent ischemic stroke. Three eligible studies were included, enrolling a total of 21,752 participants with a cumulative follow-up of 32 months. Many participants were recruited from the large-scale PROFESS trial (20,332 participants). Intervention dosing consisted of aspirin 25 mg combined with extended-release dipyridamole 200 mg administered twice daily, while the comparator was clopidogrel 75 mg once daily. In the PROFESS trial, recurrent stroke occurred in 916 patients (9.0%) in the Asp+Dp group and 898 patients (8.8%) in the clopidogrel group. The combined risk of recurrent stroke or major haemorrhagic events was comparable between groups, affecting 1,194 participants (11.7%) receiving Asp+Dp and 1,156 participants (11.4%) receiving clopidogrel. With respect to antiplatelet activity, one randomised pilot study demonstrated that Asp+Dp was associated with a delayed but significant reduction in the expression of several activation-dependent platelet receptors. Conversely, clopidogrel monotherapy was associated with earlier and more potent antiplatelet activity. Clinically, these study findings suggest that clopidogrel exerts more potent and earlier antiplatelet effects, whereas Asp+Dp produces broader but delayed downregulation of multiple platelet activation pathways. Regarding functional outcome recurrence, mortality, bleeding risk, or serious adverse events in patients with acute, mild ischemic stroke, no significant differences were observed between Asp+Dp and clopidogrel, with both regimens being practical and feasible for clinical use. In conclusion, while both therapies demonstrate comparable clinical effectiveness, further research is warranted to evaluate their long-term impact on quality of life in patients with ischemic stroke.