Key result
Carriers of the CYP2C19*2 loss-of-function allele had an increased risk of death or cardiovascular hospitalization compared to noncarriers.
Why the study?
Individual platelet responses to antiplatelet therapy depend on genetic factors including CYP2C19 and P2Y12 receptor polymorphisms, but their impact on platelet reactivity and cardiovascular outcome after PCI on clopidogrel treatment needed evaluation.
Do CYP2C19*2 and C34T P2Y12 loss-of-function alleles predict cardiovascular outcomes in stable CAD patients after PCI on clopidogrel?
Cohort (n=408)
Do CYP2C19*2 and C34T P2Y12 loss-of-function alleles predict cardiovascular outcomes in stable CAD patients after PCI on clopidogrel?
CYP2C19*2 loss-of-function alleles, but not C34T P2Y12 polymorphisms, are associated with increased platelet reactivity and worse cardiovascular outcomes in stable CAD patients on clopidogrel after PCI.
Answers are grounded in this paper and cite their sources.
May support risk stratification in observational cohorts; leaves open whether CYP2C19 genotyping improves outcomes in prospective trials.
OBJECTIVES: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. METHODS: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI. High on-treatment platelet reactivity was evaluated using the VerifyNow Assay in a subset of patients. CYP2C19*2 and C34T P2Y12 genotyping was performed by real-time polymerase chain reaction. The primary end point was the composite of death or hospitalization for cardiovascular causes, and patients were followed for a median time of 13 months. RESULTS: In the total study population, 37% were carriers of at least 1 CYP2C19*2 loss-of-function allele, and 53% were carriers of at least 1 C34T loss-of-function allele. Interestingly, homozygotes of the CYP2C19*2 loss-of-function allele had significantly increased P2Y12 reaction units (PRU) (p = 0.007). However, PRU did not differ between carriers and noncarriers of the C34T loss-of-function allele (p = 0.41). Moreover, carriers of CYP2C19*2 had an increased hazard ratio (HR) for the occurrence of the primary end point (for carriers HR = 1.96, 95% CI 1.05-3.66, p = 0.03), whereas the C34T polymorphism had no impact on the cardiovascular outcome (p = 0.17). Finally, PRU was associated with cardiovascular outcome even after adjustment for the presence of any reduced function allele polymorphism. CONCLUSIONS: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms on platelet reactivity and cardiovascular outcome in CAD patients after PCI on clopidogrel treatment. Importantly, increased platelet reactivity adversely affects the cardiovascular outcome independently of the studied polymorphisms.
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Siasos et al. (2017) conducted a cohort in Stable coronary artery disease after percutaneous coronary intervention (n=408). CYP2C19*2 loss-of-function allele vs. Noncarriers was evaluated on Composite of death or hospitalization for cardiovascular causes (HR 1.96, 95% CI 1.05-3.66, p=0.03). Carriers of the CYP2C19*2 loss-of-function allele had an increased risk of death or cardiovascular hospitalization compared to noncarriers.
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