Author Affiliations: Brigham and Women's Hospital, Boston, Massachusetts (Drs Mega and Sabatine) (email@example.com); and Scripps Translational Science Institute, La Jolla, California (Dr Topol).
To the Editor: Dr Holmes and colleagues1 conducted a meta-analysis on the important clinical question of the association between CYP2C19 genotype and cardiovascular events. However, several methodological issues warrant consideration. First, the analysis included patients in whom there is relatively little to no benefit of clopidogrel, thus curtailing the ability to observe any pharmacogenetic effect. Prior data have highlighted that in patients who have undergone coronary stenting, a setting in which the adenosine diphosphate–receptor blockade is of particular importance,2 there is a significant association between CYP2C19 loss-of-function alleles and cardiovascular outcomes, whereas there is not in patients who are managed medically or who do not have coronary disease.3- 5
Mega JL, Topol EJ, Sabatine MS. CYP2C19 Genotype and Cardiovascular Events. JAMA. 2012;307(14):1482-1485. doi:10.1001/jama.2012.444