Unmet needs in antiplatelet therapy

Abstract

Despite antiplatelet therapy, patients with acute coronary syndromes (ACS) and those undergoing coronary intervention continue to experience atherothrombotic events, indicating a need for improvement in both overall patient management and antiplatelet treatments. Limitations of clopidogrel, which is widely used in dual therapy with aspirin, include slow onset of effect, low inhibition of platelet aggregation (IPA) in many patients, interindividual variability in response, and irreversible P2Y12 binding that prevents rapid offset of effect. Higher doses of clopidogrel may overcome some of these issues, and new oral agents such as the thienopyridine prasugrel and the reversible P2Y12 antagonist AZD6140 have faster onset of action and produce greater IPA. However, antiplatelet treatment must strike a balance between reduced atherothrombotic risk and bleeding risk, and it has yet to be determined whether greater platelet inhibition will produce better clinical outcome in terms of ischaemic events with an acceptable bleeding profile. Bleeding is an inherent risk of antiplatelet therapy and an independent predictor of poor prognosis in ACS patients, a factor that should be taken into account in assessing risks and benefits of antiplatelet treatment. New reversible P2Y12 antagonists offer the potential to discontinue antiplatelet therapy closer to invasive procedures compared with the thienopyridines, thus potentially reducing both procedure-related bleeding rates and duration of exposure to atherothrombotic risk prior to procedures. Ongoing large-scale Phase 3 trials will provide important information on whether the strategies of achieving higher levels of P2Y12 inhibition and using reversible inhibitors can improve antiplatelet therapy. © The Author 2008.