Aspirin has been shown to reduce the risk of
stroke,
myocardial infarction, and death in patients with a history of
cardiovascular disease or at high risk for
cardiovascular disease. However, many individuals suffer a
stroke or other cardiovascular event despite
aspirin therapy. Data suggest that heritability contributes importantly to the antiplatelet and clinical responses to
aspirin. Candidate genes for influencing
aspirin response include those involved in platelet aggregation and in modulating
cardiovascular disease risk and progression. Although several studies have examined genetic determinants of platelet responsiveness to
aspirin, the results are largely inconsistent. Few studies have examined genetic association with clinical outcomes, including reductions in
stroke risk, with
aspirin. In perhaps the most significant pharmacogenomic study with
aspirin to date, a large primary prevention trial showed that the
apolipoprotein A genotype was associated with risk of
stroke and other cardiovascular events in women and that
aspirin eliminated this risk. These data suggest that ultimately, it may be possible to tailor
aspirin therapy based on an individual's genotype, at least for primary prevention of
stroke and cardiovascular events in women. Data on genetic determinants of response to
aspirin in secondary
stroke prevention are far less advanced. Future pharmacogenomic studies should focus on elucidating the role of genotyping in choosing appropriate antiplatelet
therapy (ie,
aspirin alone versus a
thienopyridine or combination antiplatelet
therapy) for
secondary disease prevention.