title: Impact of loading dose adjustment on platelet reactivity in homozygotes of the 2C19 2* loss of function polymorphism.
abstract: The cytochromes 2 C19 2* loss of function polymorphism has recently been shown to be associated with decreased platelet reactivity (PR) inhibition after clopidogrel loading dose (LD) and an excess in thrombotic events following percutaneous coronary intervention (PCI). We aimed to investigate if an optimal PR inhibition could be obtained in patients homozygotes for this alleles using adjusted LD of clopidogrel according to platelet reactivity monitoring. Post-treatment PR was measured using the VASP index. Dose adjustment was performed in order to obtain a PR <50% using additional clopidogrel LD. Direct sequencing was used to select homozygotes for CYP 2C19 2* alleles. Six patients with the loss of function polymorphism were recruited. The mean VASP index was 53.7 ± 16.2% after the first LD of clopidogrel. Four patients had a VASP index >50% and were therefore considered to have high on treatment PR. Using up to 3 additional 600 mg LD of clopidogrel we were able to obtain a VASP <50% in all these patients. The present study is the first to suggest that in homozygotes for CYP 2C19 2* loss of function polymorphism, increased loading dose of 55 clopidogrel is efficient to obtain an optimal level PR inhibition in patients undergoing PCI.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
authors.forename: Nathalie
authors.initials: N
authors.lastname: Palot-Bonello
authors.forename: Sébastien
authors.initials: S
authors.lastname: Armero
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D006720:Homozygote; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine