Key result
Carriers of coexisting mutational alleles of CYP2C19 and P2Y12 had a higher rate of the primary composite clinical endpoint (8.5%) compared to wild-type carriers (1.5%) at 12 months.
Why the study?
Does the presence of coexisting polymorphisms of CYP2C19 and P2Y12 worsen clopidogrel responsiveness and clinical outcomes in Han Chinese patients with acute coronary syndrome undergoing stent placement?
Cohort (n=577)
Does the presence of coexisting polymorphisms of CYP2C19 and P2Y12 worsen clopidogrel responsiveness and clinical outcomes in Han Chinese patients with acute coronary syndrome undergoing stent placement?
Absolute Event Rate: 8.5% vs 1.5%
Coexisting polymorphisms of CYP2C19 and P2Y12 synergistically impair clopidogrel responsiveness and increase the risk of adverse cardiovascular events in Chinese patients with ACS undergoing PCI.
Caution advised against genotype-guided clopidogrel changes; hypothesis-generating for combined CYP2C19/P2Y12 testing in East Asian ACS.
BACKGROUND: The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. METHODS: In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. RESULTS: Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74 ± 32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%). CONCLUSION: Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.
No takes yet. Share an insight, caveat, or question.
Tang et al. (2013) conducted a cohort in acute coronary syndrome (n=577). Coexisting mutational alleles of CYP2C19 and P2Y12 vs. Wild type genotypes of CYP2C19 and P2Y12 was evaluated on composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. Carriers of coexisting mutational alleles of CYP2C19 and P2Y12 had a higher rate of the primary composite clinical endpoint (8.5%) compared to wild-type carriers (1.5%) at 12 months.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: