Loss-of-function polymorphisms in CYP2C19 affect antiplatelet response to clopidogrel, explaining 5 to 12% of the variability in adenosine diphosphate-induced platelet aggregation.
Does genotype-based personalized therapy with clopidogrel improve outcomes in patients undergoing PCI or with ACS?
CYP2C19 loss-of-function polymorphisms significantly affect clopidogrel response but only explain a small fraction of the variability in platelet aggregation.
Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the standard of care in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) because this regimen has markedly decreased the rate of cardiovascular events. The substantial variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. Baseline demographic and clinical variables contributing to the observed variability have been identified. Besides this, research within the past decade has focused on the impact of genetic polymorphisms encoding transport systems or enzymes involved in the absorption and metabolism of these drugs. Loss-of-function polymorphisms in CYP2C19 are the strongest individual variables affecting pharmacokinetics and antiplatelet response to clopidogrel, but explain no more than 5 to 12% of the variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. No genetic variables contributing to clinical outcomes of patients treated with the newer P2Y12 receptor antagonists, prasugrel or ticagrelor, have been identified so far. This review aims to provide an update on the current status of genotype-based personalized therapy with clopidogrel.
Trenk et al. (Wed,) conducted a review in Percutaneous coronary intervention (PCI) and acute coronary syndromes (ACS). CYP2C19 loss-of-function polymorphisms was evaluated. Loss-of-function polymorphisms in CYP2C19 affect antiplatelet response to clopidogrel, explaining 5 to 12% of the variability in adenosine diphosphate-induced platelet aggregation.
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