Novel antiplatelet agents in acute coronary syndrome

For more than 10 years, dual antiplatelet therapy with aspirin and clopidogrel has remained the cornerstone of treatment for patients with acute coronary syndrome (ACS). The novel oral P2Y purinoceptor 12 (P2Y(12))-receptor inhibitors prasugrel and ticagrelor were approved by the FDA for clinical use in 2009 and 2011, respectively. These agents have a faster-acting, more-potent, and more-predictable antiplatelet effect than clopidogrel, which translates into improved clinical outcomes in patients with ACS, albeit at the expense of an increased risk of bleeding. However, some patients continue to experience adverse ischaemic events despite treatment with aspirin and a P2Y(12)-receptor antagonist, because platelets can remain activated via pathways not inhibited by these agents, such as the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin. Emerging antiplatelet therapies that might address these limitations include intravenous P2Y(12) antagonists, oral PAR-1 antagonists, and thromboxane-receptor inhibitors. In this Review, we provide an overview of these novel antiplatelet drugs, including newly approved agents and emerging compounds currently under clinical development, and also discuss evolving concepts and unmet needs related to antiplatelet therapy for the treatment of ACS.