Interindividual Variability in the Efficacy of Oral Antiplatelet Drugs: Definitions, Mechanisms and Clinical Importance

The modern era of antiplatelet therapy was founded by large clinical trials demonstrating the benefit of aspirin and clopidogrel in the treatment and prevention of acute coronary syndromes. The concept of antiplatelet drug “resistance” emerged during the 1990s with studies revealing considerable residual platelet aggregation in some patients despite aspirin treatment. In the wake of these reports, larger studies established an association between high on-treatment platelet reactivity and thrombotic events. The possible mechanisms explaining this phenomenon are manifold and reflect the complexity of platelet function, thrombus formation and cardiovascular disease. Some mechanisms apply to both drugs, while others apply only to one of them. In recent years, efforts have been made to translate this information into an improved clinical outcome by modifying antiplatelet drug regimens. Several studies investigated measurements of on-treatment platelet reactivity, but large clinical trials have failed to demonstrate substantial clinical benefit of individually tailored antiplatelet therapy according to platelet function tests. This article provides an integrated review of interindividual variability in the efficacy of aspirin and clopidogrel with particular emphasis on possible effect-modifying mechanisms and clinical implications.