Prasugrel, Māori, and personalised medicine in New Zealand.
The response to thienopyridine antiplatelet therapy is heterogeneous and is in part explained by clinical and genetic factors. A recent meta-analysis has demonstrated the clinical significance of a genetic polymorphism in the cytochrome P450 2C19 gene. Carriers of this polymorphism have a higher incidence of stent thrombosis and cardiovascular death, whilst on the thienopyridine clopidogrel. The polymorphism and rarer variants display higher carrier frequencies in ethnic groups with disproportionate cardiovascular mortality, such as Māori. Knowledge of an individual's genetic status may assist in optimising antiplatelet therapy, thereby reducing the cost of adverse events, expenditure on new medicines, and the ethnic disparities seen in healthcare outcomes. A demonstration of the cost-effectiveness of genetic testing, on a population basis, and a proven alternative, personalised strategy is required before the adoption of this technology can be advocated.
Gladding
Patrick
P
Green Lane Cardiovascular Service, Auckland City Hospital, Private Bag 92024, Victoria St West, Auckland 1142, New Zealand. patrickg@adhb.govt.nz
White
Harvey
H
Webster
Mark
M
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D010879:Piperazines / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D011110:Polymorphism, Genetic / Q000187:drug effects*; D000068799:Prasugrel Hydrochloride; D057285:Precision Medicine / Q000379:methods*; D015607:Stents; D013876:Thiophenes / Q000009:adverse effects*; D013927:Thrombosis / Q000139:chemically induced; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives; D014652:Vascular Diseases / Q000139:chemically induced*
D005819:Genetic Markers; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine