Prasugrel in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention
Prasugrel in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention
Currently, dual antiplatelet therapy with aspirin and clopidogrel represents the key treatment strategy for the prevention of ischemic events in patients with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). However, there is a broad inter-individual response variability to such treatment strategy, and a considerable number of patients persist with inadequate platelet inhibition, which has been associated with an increased risk of ischemic events. Overall, these findings underscore the need for novel antiplatelet agents able to achieve greater platelet inhibition; this can potentially reduce ischemic event rates. Prasugrel (CS-747; LY 640315), a novel third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet adenosine diphosphate P2Y12 receptor. Laboratory studies have shown prasugrel to be associated with more prompt, potent and predictable degrees of platelet inhibition compared with clopidogrel. In a large-scale clinical study, which was comprised of high-risk ACS patients undergoing PCI, prasugrel was shown to significantly reduce the short- and long-term risk of ischemic events, including stent thrombosis. However, such significant reduction in ischemic events occurred at the expense of a higher risk of bleeding. Recent clinical trial data analyses have led to a better understanding of the efficacy and safety of prasugrel. This article reviews the currently available data regarding the efficacy and safety of prasugrel in ACS patients.
Platelets are key players in the pathogenesis of thrombotic complications taking place at the site of atherosclerotic plaque disruption, which may either occur spontaneously, as in patients with acute coronary syndrome (ACS) or be iatrogenically induced, as in patients undergoing percutaneous coronary intervention (PCI). Therefore, platelet-inhibiting agents are essential in these clinical settings. Clopidogrel, a second-generation thienopyridine that selectively inhibits the ADP P2Y12 receptor, is the antiplatelet drug of choice used in combination with aspirin for the secondary prevention of ischemic events, including stent thrombosis, in ACS/PCI patients. Clinical trials have shown adjunctive use of clopidogrel in addition to aspirin to be associated with better short- and long-term clinical outcomes in patients with ACS, either with or with ST-segment elevation, regardless of coronary revascularization. However, despite these benefits, a considerable number of patients continue to experience thrombotic events. Accumulating evidence has shown that this may be, in part, attributed to inadequate clopidogrel-induced platelet inhibition. In fact, a broad range of inter-individual response variability in the degree of platelet P2Y12 blockade induced by clopidogrel has been shown, and patients who persist with high platelet reactivity despite adjunctive clopidogrel have an increased atherothrombotic risk. These observations underscore the need for platelet P2Y12 inhibitors with more-potent and less-variable response profiles. There are several novel P2Y12 inhibitors under clinical investigations, which present these properties. Among these, prasugrel (CS-747; LY 640315), a third-generation oral thienopyridine, is at the most advanced stage of clinical investigation. This article reviews the currently available data regarding the efficacy and safety of prasugrel in the setting of ACS.
Abstract and Introduction
Abstract
Currently, dual antiplatelet therapy with aspirin and clopidogrel represents the key treatment strategy for the prevention of ischemic events in patients with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). However, there is a broad inter-individual response variability to such treatment strategy, and a considerable number of patients persist with inadequate platelet inhibition, which has been associated with an increased risk of ischemic events. Overall, these findings underscore the need for novel antiplatelet agents able to achieve greater platelet inhibition; this can potentially reduce ischemic event rates. Prasugrel (CS-747; LY 640315), a novel third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet adenosine diphosphate P2Y12 receptor. Laboratory studies have shown prasugrel to be associated with more prompt, potent and predictable degrees of platelet inhibition compared with clopidogrel. In a large-scale clinical study, which was comprised of high-risk ACS patients undergoing PCI, prasugrel was shown to significantly reduce the short- and long-term risk of ischemic events, including stent thrombosis. However, such significant reduction in ischemic events occurred at the expense of a higher risk of bleeding. Recent clinical trial data analyses have led to a better understanding of the efficacy and safety of prasugrel. This article reviews the currently available data regarding the efficacy and safety of prasugrel in ACS patients.
Introduction
Platelets are key players in the pathogenesis of thrombotic complications taking place at the site of atherosclerotic plaque disruption, which may either occur spontaneously, as in patients with acute coronary syndrome (ACS) or be iatrogenically induced, as in patients undergoing percutaneous coronary intervention (PCI). Therefore, platelet-inhibiting agents are essential in these clinical settings. Clopidogrel, a second-generation thienopyridine that selectively inhibits the ADP P2Y12 receptor, is the antiplatelet drug of choice used in combination with aspirin for the secondary prevention of ischemic events, including stent thrombosis, in ACS/PCI patients. Clinical trials have shown adjunctive use of clopidogrel in addition to aspirin to be associated with better short- and long-term clinical outcomes in patients with ACS, either with or with ST-segment elevation, regardless of coronary revascularization. However, despite these benefits, a considerable number of patients continue to experience thrombotic events. Accumulating evidence has shown that this may be, in part, attributed to inadequate clopidogrel-induced platelet inhibition. In fact, a broad range of inter-individual response variability in the degree of platelet P2Y12 blockade induced by clopidogrel has been shown, and patients who persist with high platelet reactivity despite adjunctive clopidogrel have an increased atherothrombotic risk. These observations underscore the need for platelet P2Y12 inhibitors with more-potent and less-variable response profiles. There are several novel P2Y12 inhibitors under clinical investigations, which present these properties. Among these, prasugrel (CS-747; LY 640315), a third-generation oral thienopyridine, is at the most advanced stage of clinical investigation. This article reviews the currently available data regarding the efficacy and safety of prasugrel in the setting of ACS.