Abstract
Aspirin is the foundation antiplatelet therapy for patients at risk of cardiovascular events. The thienopyridine, clopidogrel, is modestly more effective than aspirin and in patients with stroke seems to be as effective as the combination of aspirin and dipyridamole. The addition of clopidogrel to aspirin further reduces the risk of cardiovascular events in patients with acute coronary syndromes and those who undergo percutaneous coronary intervention, but uncertainty remains about whether this combination has incremental efficacy over clopidogrel monotherapy in patients with stroke or peripheral arterial disease. Clopidogrel has pharmacological limitations that have prompted the search for more effective ADP-receptor antagonists. Promising results have been achieved with the thienopyridine, prasugrel, which has been compared with clopidogrel in patients treated with aspirin. The nonthienopyridine P2Y12 inhibitors AZD6140 and cangrelor are presently being evaluated in phase III, randomized, controlled trials.
Key Points
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Long-term clopidogrel is modestly more effective than aspirin
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Combined antiplatelet therapy with clopidogrel and aspirin reduces the risk of recurrent cardiovascular events in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention
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Clopidogrel does have some limitations: slow onset of action; variable inhibition of platelet function; lack of reversibility; and undefined optimum loading dose
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When administered immediately before percutaneous coronary intervention, prasugrel—a more rapid and more potent P2Y12 receptor inhibitor than clopidogrel—reduces nonfatal myocardial infarction but increases major bleeding events
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AZD6140 and cangrelor—reversible, nonthienopyridine P2Y12 inhibitors currently being tested—have a more rapid onset and cessation of action than clopidogrel and could reduce acute bleeding risk in patients with acute coronary syndromes requiring early CABG surgery
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Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.
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JW Eikelboom has received speakers honoraria and grant/research support from Bayer, Bristol-Myers Squibb and sanofi-aventis.
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Supplementary information
Supplementary Figure 1
Reference list for clinical trials that evaluated ticlopidine, featured in Table 2. Supplementary figure provided as an eps file. (JPG 56 kb)
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Raju, N., Eikelboom, J. & Hirsh, J. Platelet ADP-receptor antagonists for cardiovascular disease: past, present and future. Nat Rev Cardiol 5, 766–780 (2008). https://doi.org/10.1038/ncpcardio1372
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DOI: https://doi.org/10.1038/ncpcardio1372
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