Overcoming clopidogrel resistance with higher dose

Overcoming clopidogrel resistance with higher dose: It is now well known that variations in CYP2C19 gene affect the response to clopidogrel. ELEVATE-TIMI 56 by Jessica L Mega, Willibald Hochholzer, Andrew L Frelinger 3rd, Michael J Kluk, Dominick J Angiolillo, Dean J Kereiakes, Steven Isserman, William J Rogers, Christian T Ruff, Charles Contant, Michael J Pencina, Benjamin M Scirica, Janina A Longtine, Alan D Michelson and Marc S Sabatine [1] evaluated whether this clopidogrel resistance due to loss of function mutation in CYP2C19 gene can be overcome by higher doses of clopidogrel. ELEVATE-TIMI 56 was a randomized double blind trial involving thirty two sites which enrolled 333 genotyped patients. The investigators found that tripling the dose of clopidogrel to 225 mg per day maintenance dose produced the same level of reduction of platelet reactivity in heterozygotes as compared to 75 mg per day in non carriers of the mutation. But in homozygotes for the mutation, even 300 mg per day maintenance dose did not have similar reduction in platelet reactivity.

Reference

1. Jessica L Mega, Willibald Hochholzer, Andrew L Frelinger 3rd, Michael J Kluk, Dominick J Angiolillo, Dean J Kereiakes, Steven Isserman, William J Rogers, Christian T Ruff, Charles Contant, Michael J Pencina, Benjamin M Scirica, Janina A Longtine, Alan D Michelson, Marc S Sabatine. Dosing Clopidogrel Based on CYP2C19 Genotype and the Effect on Platelet Reactivity in Patients With Stable Cardiovascular Disease. JAMA. 2011 Nov 23;306(20):2221-8.