Emerging issues and new pharmacologic options for P2Y12 inhibition in acute coronary syndromes
It is with great pleasure that we are able to provide you with the proceedings from the Special Symposium ‘Emerging issues and new pharmacologic options for P2Y12 inhibition in acute coronary syndromes’, presented at the International Society of Thrombosis and Haemostasis (ISTH) XXIst Congress, 2007. Both the symposium and this supplement were made possible by an unrestricted educational grant from AstraZeneca.
Since 1980s, aspirin (acetylsalicylic acid) has been first-line treatment for prevention of ischaemic events in patients with acute and chronic coronary artery disease. The development of P2Y12 ADP-receptor antagonists and their use as dual antiplatelet therapy with aspirin have further reduced the risk of cardiovascular events in acute coronary syndromes (ACS) and in percutaneous coronary intervention- and stent-treated patients. However, despite receiving combination therapy of aspirin and the thienopyridine clopidogrel, many patients with ACS still experience thrombotic events and suffer complications due to unwanted bleeding. This supplement examines the strengths and weaknesses of current antiplatelet therapies and explores emerging pharmacotherapeutic options that may address these unmet needs.
In the first manuscript, ‘Unmet needs in antiplatelet therapy’, Jean-Pierre Bassand examines the gaps in contemporary antiplatelet therapy from both clinical and research standpoints. In examining issues such as variability of response, intermediate inhibition of platelet aggregation, and slow offset of effect, he highlights the need for further research and development of improved therapeutic agents, especially in relation to the importance of possible bleeding complications associated with existing therapies.
The second manuscript, ‘Medical consequences of antiplatelet therapy among patients undergoing coronary artery bypass graft (CABG) surgery’ by Richard C. Becker, highlights the risks of serious perioperative bleeding and associated complications in CABG patients also receiving antiplatelet therapy. This manuscript focuses on reversible agents as a possible solution to the considerable risk of bleeding posed by therapy with irreversible thienopyridines in these patients.
The third manuscript ‘Optimising antiplatelet therapy’ by Hans van Giezen, explores how the challenges posed by the unmet needs in antiplatelet therapy may potentially be addressed through the development of new molecules in the laboratory. The novel characteristics and mechanisms of action of these emerging molecules, and their possible clinical implications, is the focus.
In the fourth manuscript, ‘New developments in antiplatelet therapy’, Robert F. Storey provides a detailed overview of the pharmacodynamic effects of the P2Y12 antagonists currently in Phase 3 clinical trials, including cangrelor, AZD6140, and the thienopyridine prasugrel, which has just completed its Phase 3 trial. The results of this completed trial, TRITON TIMI-38, are discussed, highlighting the increased reduction in ischaemic events at the cost of an increased number of both TIMI major and fatal bleeding events with prasugrel, as compared to clopidogrel.
The last manuscript, ‘Role and development of antiplatelet therapy in the DES era’ by Lars Wallentin, addresses the current debate regarding the risks of stent thrombosis and the impact that a low or variable response to clopidogrel may have on these risks. The importance of emerging alternative treatments for reducing the risk of stent thrombosis is emphasised, especially in light of the significant improvement in outcomes when prasugrel was compared to clopidogrel in TRITON TIMI-38 in the prevention of this complication.
Taken together, these manuscripts provide the reader with an update of current and emerging options in antiplatelet therapy. It is hoped that these proceedings will also provide helpful insights into understanding and evaluating the rapidly expanding field of antiplatelet and antithrombotic treatments.
Uppsala Clinical Research Centre
Uppsala University, Uppsala
Sweden
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