Resistance to antiplatelet drugs : molecular mechanisms and laboratory detection

Summary. The definition resistance to antiplatelet drugs should be limited to situations in which failure of the drug to hit its pharmacological target has been documented by specific laboratory tests. Aspirin resistance, as determined by specific tests (e.g. serum thromboxane B2), appears to be rare (1–2%) and, in most instances, is caused by poor compliance. In contrast to aspirin, studies that used specific tests tomeasure the pharmacological effect of thienopyridines [e.g. vasodilatorstimulated phosphoprotein (VASP)] showed a wide variability of responses to these drugs, with significant proportions of subjects (15–30%) who are very poor responders. Interindividual differences in the extent of metabolism of thienopyridines to their active metabolites is the most plausible mechanism for the observed inter-individual variability in platelet inhibition. The demonstration that some patients may be resistant or poor responders to the pharmacological effect of antiplatelet drugs, has prompted the need of laboratory monitoring of antiplatelet therapy. However, many published studies have been performed using unspecific tests of platelet function, which identify patients on antiplatelet treatment with high residual platelet reactivity, which is not necessarily because of resistance to antiplatelet drugs. Despite this drawback, identification of patients with high residual platelet reactivity may be useful to predict their risk of atherothrombotic events. However,many studies still need to be carried out to identify the ideal laboratory test and to answer basic questions on its clinical utility and cost-effectiveness, before monitoring antiplatelet therapy can be recommended in the clinical practise.Until then, monitoring of antiplatelet therapy should be considered for investigational purposes only.