Expert Commentary & Five-year View
Improvement in our understanding of the mechanisms leading to platelet activation and their involvement in cardiovascular thrombosis has led to the development of potent antiplatelet drugs with well documented efficacy in the prevention and treatment of atherothrombotic disease. Currently, physicians have a panel of various platelet inhibitors, which enable them to tailor the most appropriate anti-thrombotic therapy to the individual patient and risk situation.
The P2Y12 receptor antagonists that are currently being used in clinical practice are the thienopyridines clopidogrel and prasugrel. Recently, there has been great interest in the novel ADP P2Y12 receptor antagonists prasugrel and ticagrelor that are used in clinical practice. Although these antagonists may show greater efficacy compared to clopidogrel, there may be issues with safety, and bleeding in particular. Therefore, clinical experience progressively obtained by physicians using these drugs in the daily clinical practice will finally prove the usefulness of these new agents compared with clopidogrel. Furthermore, the clinical usefulness of the novel P2Y12 antagonists elinogrel and cagrelor is awaiting to be proved.
Two PAR-1 antagonists have been studied in Phase III clinical trials. Very recently, the results of the TRA-2P-TIMI 50 study for vorapaxar have been published. These results showed that the addition of vorapaxar to standard antiplatelet therapy reduced the risk of adverse cardiovascular events; however, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage, with the latter occurring most frequently in patients with a history of stroke. Therefore, further studies with vorapaxar or even with newer PAR-1 antagonists need to be undertaken before final conclusions are drawn on the clinical usefulness of these drugs.
Overall, the improved prevention and treatment of platelet-dependent thrombosis with new antiplatelet agents is associated with an increased bleeding risk. Thus the ultimate goal of drug discovery in the field of antiplatelet therapy should be the discovery of agents with high anti-thrombotic efficiency and low adverse hemorrhagic side effects. In this regard, novel agents that target other platelet receptors such as the vWF or the collagen receptors are currently under investigation in preclinical studies. Promising data have been obtained with these agents; however, their usefulness in the clinical setting needs to be proved in large-scale clinical trials.
Expert Rev Clin Pharmacol. 2012;5(3):319-336. © 2012 Expert Reviews Ltd.