CYP2C19 genotype-guided antiplatelet therapy in a patient with clopidogrel resistance.
We report a switch in antiplatelet medication based on platelet function and CYP2C19 genotype test results in a 74-year-old man with severe coronary arterial disease. Upon bare metal stent implantation at age 66, clopidogrel therapy (75 mg/ day) was initiated to supplement aspirin. Over the next eight years, the patient required multiple percutaneous coronary interventions for de novo coronary stenosis and in-stent restenosis. Platelet reactivity measured while on clopidogrel therapy was high, consistent with clopidogrel resistance. CYP2C19 genotype testing then revealed homozygosity for the *2 null allele. The *2/*2 designation indicates poor metabolizer status, indicating deficient capacity of the cytochrome p450 2C19 enzyme for activation of clopidogrel. A medication switch to prasugrel,which does not rely on activation by the 2C19 enzyme, reduced platelet reactivity by 86%. The patient has suffered no cardiovascular events in the 18 months since initiation of prasugrel therapy.
Hartford Hospital, Hartford, USA. mrai@harthosp.org
Mridula
M
Rai
Richard L
RL
Seip
Ankur
A
Gupta
Raymond G
RG
McKay
Jeffrey
J
Hirst
Paul D
PD
Thompson
Gualberto
G
Ruaño
D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000235:genetics* / Q000628:therapy; D065731:Cytochrome P-450 CYP2C19; D004351:Drug Resistance / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D010879:Piperazines / Q000627:therapeutic use; D015539:Platelet Activation / Q000187:drug effects* / Q000235:genetics; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D015607:Stents; D013876:Thiophenes / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin