Abstract 2126: CYP2C19 Genetic Variants and Clinical Outcomes With Clopidogrel: A Collaborative Meta-Analysis
Introduction: Several studies have recently evaluated the relationship between CYP2C19 variants and risk of adverse cardiovascular (CV) events in the setting of clopidogrel treatment. However, risk estimates from individual studies have wide confidence intervals and the relative effects for heterozygotes and homozygotes remain controversial.
Methods: Nine studies evaluating the association between reduced-function CYP2C19 alleles (predominantly *2) and outcomes in patients (91% underwent PCI, 65% presented w/ACS) treated w/clopidogrel were included in a collaborative meta-analysis. 9684 subjects contributed to MACE (major adverse CV events) and 5772 to stent thrombosis. Data were combined using a random-effects model with weighting based on inverse variance.
Results: Of 9684 subjects, 71.5% were wildtype and 28.5% carriers (26.3% heterozygotes, 2.2% homozygotes). Carriers vs non-carriers of a reduced-function CYP2C19 allele had a significantly increased risk of MACE (RR 1.61, Figure⇓), with risk evident in both heterozygotes (RR 1.50) and homozygotes (RR 1.81). Moreover, carriers had a 2.76 fold increased risk of stent thrombosis, with 2.51 and 4.78 fold increased risk in heterozygotes and homozygotes.
Conclusion: Carriers of a reduced-function CYP2C19 allele are at a greater than 50% increased risk of adverse CV events and a nearly 3 fold increased risk of stent thrombosis in the setting of treatment with clopidogrel. This elevated risk is apparent in both heterozygotes and homozygotes of a reduced-function CYP2C19 allele. Thus, genetic testing identifies nearly 30% of patients who are less likely to be protected from recurrent ischemic events by clopidogrel.