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March 14, 2012

Clopidogrel Dosing Based on Genotype

Author Affiliations

Author Affiliations: Department of Cardiology, Patras University Hospital, Rio, Patras, Greece (dalex@med.upatras.gr).

JAMA. 2012;307(10):1024-1025. doi:10.1001/jama.2012.281

To the Editor: Dr Mega and colleagues1 presented a study showing that increasing the clopidogrel dose resulted in platelet inhibitory effects in patients heterozygous for the CYP2C19*2 loss-of-function allele, but not in homozygotes. We consider a few points that require clarification.

Platelet reactivity was assessed at least 1 month after myocardial infarction (MI), percutaneous coronary intervention (PCI), or both. However, it is well recognized that most events, including stent thrombosis, occur early, within 30 days of PCI. In the Platelet Inhibition and Patient Outcomes (PLATO) genetic substudy,2 the event rate at 30 days was higher in clopidogrel-treated patients with CYP2C19 alleles than those without CYP2C19 alleles, leading to earlier separation of event rates between the ticagrelor and clopidogrel groups in patients with loss-of-function alleles. In contrast, beyond 30 days, no difference in event rates between treatment groups for patients with any loss-of-function allele was observed. Therefore, genotyping and appropriate clopidogrel dose escalation outside the setting of MI and PCI may not provide incremental clinical utility.

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