Summary
The dual antiplatelet therapy consisting of aspirin and the ADP-receptor blocker clopidogrel
is the current standard medication after acute coronary events. However, clopidogrel
is characterised by a high interindividual response variability, insufficient inhibition
of platelet aggregation in a significant number of patients, relatively slow onset
of efficacy and potential interaction with different co-medication via diverse hepatic
cytochrome enzymes. In various trials, response variability of clopidogrel was translated
into a higher rate of recurrent cardiovascular events. Different clinical and non-genetic
factors contribute to the phenomenon of clopidogrel response variability. An individualised
antithrombotic pharmacotherapy taking these factors into account, including the definition
of status of response, verification of the efficacy by standardised platelet function
testing, intensified or alternative platelet inhibition would be the ultimate goal
for patients treated with clopidogrel. Currently, new drugs are on the way and promise
a more consistent efficacy and smaller amount of response variability. However, the
bleeding risk in subgroups of patients and further side effect profile remains to
be clearly defined. Therefore, risk stratification models are warranted to identify
patients who benefit from personalised pharmacotherapy in terms of improved clinical
net benefit. In this review, we discuss treatment failure of clopidogrel based on
platelet function testing, the mechanism of established and new ADP-blockers as well
as new therapeutic principles.
Keywords
ADP-receptor blockers - thienopyridines - clopidogrel - response variability - prasugrel
- platelet function testing
