Determinants of the interindividual variability in response to antiplatelet drugs.
The aim of this review article is to discuss the main determinants of the interindividual variability in response to antiplatelet agents. The main sources of pharmacokinetic and pharmacodynamic variability are reviewed, with particular emphasis on aspirin and clopidogrel. The term 'resistance' is uninformative of the mechanism(s) underlying interindividual variability in response to these antiplatelet agents, and is potentially misleading. Increased awareness of the distinct factors potentially interfering with the desired antiplatelet effects of aspirin or clopidogrel, particularly avoidable drug interactions, may ultimately result in better patient management than requesting unnecessary costly tests of platelet function. Similarly, new studies addressing the interindividual variability in response to these antiplatelet agents should rely upon mechanism-based biochemical end-points rather than platelet aggregation measurements. As with any drug used to prevent atherothrombosis, treatment 'failure' can occur with aspirin or clopidogrel perhaps not surprisingly, given the multifactorial nature of atherothrombosis. There is no scientific basis for changing antiplatelet therapy in the face of a treatment 'failure', as we cannot be sure whether a second vascular event occurring in the same patient will reflect the same pathophysiological event that led to the first. Moreover, we have no controlled evidence that changing therapy is a more effective strategy than maintaining an evidence-based therapy.
Rocca
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Center of Excellence on Aging, G. D'Annunzio University Foundation, Chieti, Italy.
Patrono
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D004347:Drug Interactions; D004351:Drug Resistance; D006801:Humans; D008954:Models, Biological; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D012306:Risk; D013927:Thrombosis / Q000188:drug therapy*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin