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.
Department of Cardiology, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark.
Morten
M
Würtz
Erik Lerkevang
EL
Grove
D000284:Administration, Oral; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D000077144:Clopidogrel; D015897:Comorbidity; D004347:Drug Interactions; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D006801:Humans; D055118:Medication Adherence; D018579:Patient Selection; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin