Interindividual Variability in response to aspirin and P2Y12 blockers in patients at high cardiovascular risk-the state of the evidence

In an ideal world, 100 patients given the same dose of the same drug would display the same pharmacological response, implying identical pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body). The real world, however, is one of interindividual pharmacokinetic and pharmacodynamic variability. How this determines the response to aspirin and platelet adenosine diphosphate receptor (P2Y12) blockers is the subject of this review, designed to help cardiologists critically assess the overwhelming literature on “resistance” to these antiplatelet drugs and gauge the utility and limitations of current biochemical, functional, and genetic tests of individual drug response. The term “resistance” is uninformative of the mechanism(s) behind interindividual variability in response and potentially misleading, implying we have a standardized method of measurement directly reflecting clinical efficacy that can dictate changes in antiplatelet therapy. In fact, the relationship between the functional indices of platelet capacity measurable ex vivo and the occurrence of platelet activation and inhibition in vivo is far from established. We therefore suggest abandoning the term “resistance” if we are to advance our understanding of the complex determinants of interindividual variability in response to aspirin and P2Y12 blockers discussed here and elsewhere in this issue.