Stroke prevention: from available antiplatelet drugs to novel molecular targets

Stroke is the third most common cause of death in the industrialized countries and adequate primary and secondary prevention strategies are mandatory. In addition to lifestyle-changes and correction of cardiovascular risk factors, the mainstay of the atherothrombotic stroke prevention is represented by antiplatelet treatment. Although aspirin and thienopyridines have proved their efficacy in the prevention of arterial thrombotic events, limited efficacy, increased risk of bleeding, significant inter-individual variability in the response and extended duration of action that cannot be reversed if the need for haemostasis or emergency surgery arises represent major limitations of these drugs. Moreover, despite recommendations and guidelines about stroke prevention, registries data clearly suggest an underuse of antiplatelet drugs, mainly because of bleeding episodes fear. At variance with newer anticoagulant drugs, which showed a series of advantages as compared with the traditional warfarin treatment, newer antiplatelet drugs have only partially overcome these limitations. Although ad hoc studies on their efficacy in the stroke prevention are currently lacking, newer antiplatelet agents (mainly ticagrelor and prasugrel) do not provide a significant better protection over and above aspirin and/or clopidogrel in the prevention of atherothrombotic stroke. In addition, a significantly increased bleeding risk has been reported in subjects receiving these new thienopyridines. According to these data, the identification of further molecular targets is needed, in order to design future antiplatelet drugs. In this review, after summarizing major literature data about traditional and newer antiplatelet drugs, we will specifically focus on novel potential target candidates for antiplatelet therapy.