Dual antiplatelet
therapy with
aspirin and
clopidogrel is the standard of care for patients with
acute coronary syndrome (ACS) and those undergoing
percutaneous coronary intervention (PCI). It is well established that inhibition of platelet aggregation reduces the risk of recurrent thrombotic events and
stent thrombosis. However, some patients show a reduced antiplatelet response to standard
clopidogrel loading (300 mg) and maintenance (75 mg day(-1)) doses, which has been associated with poorer patient outcomes. Pharmacodynamic and pharmacokinetic studies show that higher-than-standard
clopidogrel dosing strategies facilitate more rapid platelet inhibition of a greater intensity as a result of greater plasma concentrations of the
clopidogrel active metabolite. Recently completed studies suggest that in patients with ACS undergoing PCI, higher-than-standard
clopidogrel dosing regimens provide greater inhibition of platelet function and improved clinical outcomes with a small but significant increase in major
bleeding. Newer, more potent
antiplatelet agents such as
prasugrel and
ticagrelor are other alternative strategies that result in more rapid, greater inhibition of platelet function and better outcomes than standard-dose
clopidogrel. Whether platelet reactivity-guided
therapy or genotyping for
cytochrome P450 polymorphisms is useful in managing patients needs to be further defined. Most importantly, early and effective antiplatelet
therapy results in the best short- and long-term outcomes for patients with ACS or those undergoing PCI.