Understanding response to clopidogrel

A genetic basis for the variable clinical response to the anti-blood clot drug clopidogrel is presented this week in Nature Medicine. This finding may be exploited to assess in advance the clinical efficacy of this popular drug in each patient.

Clopidogrel is one of the most widely prescribed blood clotting medicines worldwide, but its efficacy is hampered by patient differences in the metabolic processing necessary for the drug to become active. This variability has been attributed to genetic factors, but the specific genes underlying clopidogrel activation are disputed.

Dirk Taubert and his colleagues report that paraoxonase-1 (PON1) is the crucial enzyme for clopidogrel activation. The authors tested the clinical relevance of genetic variants of PON1 in a group of patients with coronary artery disease who underwent stent implantation and received clopidogrel to prevent thrombosis. Patients with the PON1 QQ192 genotype showed a higher risk of stent thrombosis than patients with the RR192 genotype. The QQ192 patients also had lower PON1 plasma activity, lower plasma concentrations of active drug and less platelet inhibition than the RR192 group.

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doi: 10.1038/nm.2281

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