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Keywords:

  • stroke prevention;
  • aspirin;
  • clopidogrel;
  • dipyridamole;
  • novel antiplatelet drugs

Abstract

Clinical Development Phases I-III Regulatory, Quality, Manufacturing

Pharmacological stroke prevention with antithrombotic drugs has evolved since the 1970s. The mechanism of action of the classical antiplatelet drugs is based on the inhibition of one of three strategic platelet activation pathways related to cyclooxygenase action (aspirin), activation of glycoprotein IIb/IIIa by adenosine-diphosphate via the P2Y12 receptor (thienopyridines), and inhibition of platelet phosphodiesterase (dipyridamole). The effectiveness of antiplatelet drugs was proved in multiple large clinical trials that became the basis for current recommendations. However, the efficacy and especially safety of these drugs are not satisfactory, and research on novel treatment modalities is ongoing. Recently completed or continuing clinical trials dedicated to secondary stroke prevention manifest two directions. One of them involves the search for new antiplatelet drugs and evaluation of their efficacy. The other one is targeted at evaluation of efficacy and safety of dual or even triple antiplatelet therapy. The future of antithrombotic treatment involves platelet function modulation through interactions with the platelet signal transduction pathways. The most advanced studies pertain to inhibitors of platelet kinases: spleen tyrosine kinase (Syk), phosphotidylinositol 3-kinase, protein kinase C delta and p38 mitogen-activated protein kinase. Another new therapeutic target may be platelet microRNA particles because their abnormal expression may cause disturbed hemostasis. In the future, it seems that targeted and individualized therapy based on modification of genetically and environmentally conditioned factors that are crucial for prothrombotic properties of platelets might bring definite benefits. Hence, further activities should be focused on designing tools that allow the selection of the antiplatelet therapy balancing benefits and risks as well as cost.