Clopidogrel in combination with
aspirin is the recommended standard of care for reducing the occurrence of cardiovascular events in patients presenting with
acute coronary syndromes; these protective effects of
clopidogrel have been shown both in patients undergoing
percutaneous coronary intervention (PCI) and in those treated with medical
therapy alone. However, significant shortcomings still exist, including a delayed onset of action in platelet inhibition, individual response variability (with some patients being frankly hyporesponsive), and a prolonged time to recovery of platelet function following
cessation of treatment. Among these,
clopidogrel hyporesponsiveness seems to be particularly important, as a growing body of evidence suggests that residual platelet reactivity on
clopidogrel is associated with a significant increase in the risk of developing adverse clinical events.
Prasugrel is a novel, third-generation oral
thienopyridine that is a specific, irreversible antagonist of the platelet
adenosine 5'-diphosphate P2Y12 receptor.
Prasugrel has more potent antiplatelet activity, faster onset of action, and less interpatient variability as compared to
clopidogrel. These pharmacodynamic properties led
prasugrel to be more effective in preventing ischemic events in patients with
acute coronary syndromes undergoing PCI in the setting of the recent TRITON-TIMI 38 study. However, the greater protective effects toward ischemic events were partially counterbalanced by an increased risk of
bleeding, particularly in patients with history of
transient ischemic attack/
stroke, in those with
body weight <60 kg and in those older than 74 years. A favorable net clinical benefit of
prasugrel compared with
clopidogrel has been shown.