New Anti-Thrombotic Drugs in Acute Coronary Syndromes and Percutaneous Coronary Intervention. The Role of Prasugrel, Ticagrelor and Cangrelor

Abstract

Platelet activation and subsequent aggregation play a dominant role in the propagation of arterial thrombosis and consequently are the key therapeutic targets in the management of acute coronary syndrome (ACS). Platelets can be activated through many pathways. Inhibition of such a pathway results only in partial attenuation of platelet function. Aspirin irreversibly blocks platelet cyclooxygenase (COX-1), inhibits thromboxane A2 formation and induces a permanent functional inhibition in platelets. As a consequence, aspirin use has been shown to safely reduce ischemic events throughout the spectrum of clinical manifestations of coronary artery disease (CAD). Therefore, aspirin is part of the standard treatment given to patients with CAD, including those undergoing percutaneous coronary intervention (PCI).

Despite the inhibition of cyclooxygenase by aspirin, platelet activation can still occur through thromboxane-independent pathways, leading to aggregation of platelets and formation of thrombin. Thus, inhibition of an additional pathway of platelet activation could further reduce platelet activity. As a consequence, the antagonists of P2Y12 receptor have emerged as a major therapeutic tool in ACS. Clopidogrel, an oral P2Y12 receptor inhibitor, added to standard regimen with aspirin further reduces the short- and long-term risk of death and ischemic complications in high-risk settings, such as patients with an ACS and those undergoing PCI. However, the pharmacokinetic and pharmacodynamic effects of clopidogrel are highly variable and may be influenced by genetic polymorphisms, which translate into differential pharmacodynamics and therapeutic responses, leading to the notion of clopidogrel “nonrespondersâ€. Two newer oral adenosine diphosphate (ADP) blockers, prasugrel and ticagrelor, have been associated with less interpatient variability and a more potent platelet-aggregation response. Prasugrel was superior to clopidogrel in patients with ACS who were undergoing PCI, and ticagrelor was superior to clopidogrel in patients with ACS...(excerpt)