Poster No. 052 The Influence of the CYP2C9 polymorphisms on the treatment with clopidogrel: combined data from the POPular Genetics & POPular AGE trials

Abstract Background The CYP2C9-enzym plays a role in the metabolization of clopidogrel. In patients treated with clopidogrel, carriage of a CYP2C9 loss-of-function (LoF) allele has been associated with attenuated pharmacokinetics leading to a diminished pharmacodynamic response and increased risk for stent thrombosis. Material and methods We aimed to determine the effect of the CYP2C9*2 and *3 LoF-alleles on thrombotic events and clopidogrel treatment discontinuation. A post-hoc analysis was performed in patients with available CYP2C9 genotype status included in the POPular Genetics and POPular Age trials, which enrolled patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction, respectively. The primary thrombotic outcome was a composite of cardiovascular death, myocardial infarction or stroke. Results The CYP2C9 genotype was available in 2,257 patients, of which 878 were treated with clopidogrel (352 [40%] CYP2C9 LoF-allele carriers and 526 [60%] CYP2C9 LoF-allele noncarriers). There were no significant differences between CYP2C9 LoF-allele carriers and noncarriers for the combined thrombotic outcome (6.3% vs. 5.9%, HR 1.17 [0.67–2.03], P = 0.58), and the individual thrombotic outcomes. No differences were seen in clinically relevant bleeding (Bleeding Academic Research Consortium [BARC] 2–5 bleeding) as well as major bleeding (BARC 3 or 5 bleeding). Discontinuation rates for clopidogrel due to side-effects were numerically lower in CYP2C9 LoF carriers compared noncarriers (1.4% vs. 3.2%, HR 0.54 [0.26–1.13], P = 0.10), however this difference was not statistically significant. Conclusions Carriage of the CYP2C9 *2 or *3 LoF-alleles did not show an association with an increased thrombotic risk in patients treated with clopidogrel. Funding ZonMW.