Abstract 14831: Considering Abcb1 Genotype In Addition To Cyp2c19 Loss-of-function Allele Allows Better Prediction Of 1-year Clinical Outcomes Than Each One In Clopidogrel On-treatment Patients Who Underwent Pci With Drug-eluting Stent
Introduction Combined effect of ABCB1 3435 TT genotype and CYP2C19 loss-of-function allele on 1-year clinical outcomes in real-world PCI cohort have not been studied.
Methods We retrospectively enrolled 2188 patients (1656 [75.7%] angina and 532 [24.3%] AMI patients) who received a loading dose of 600mg clopidogrel followed by daily 75mg maintenance dose for at least 1-year after PCI between 2005 to 2009. We tested the association of polymorphism of 6 genes (CYP2B6, CYP2C19, CYP3A4, CYP3A5, ABCB1, P2Y12) with the primary end point of major adverse cardiac and cerebrovascular events (MACCE; including death from any cause, nonfatal MI, or stroke) during 1-year follow-up.
Results Patients with MACCE showed older, higher prevalence of HBP/CRF/CYP2C19 poor metabolizer (PM) (*2/*2, *2/*3, *3/*3) genotype, more left main disease, and more diagnosis of MI than patients without MACCE. On multivariable Cox analysis, age≥65 years (HR; 3.65, 95% CI; 2.29-6.49), diagnosis of MI (HR; 2.72, 95% CI; 1.75-4.23), CRF (HR; 6.32, 95% CI; 3.80-10.51), and CYP2C19 PM (HR; 1.87, 95% CI; 1.12-3.12) were identified as predictors of MACCE. ABCB1 3435 TT genotype had no statistical significance on Cox regression model. Notably, when CYP2C19 PM was combined with ABCB1 3435C◊T polymorphism, presence of ABCB1 3435 TT genotype had a statistical significance (PM+ABCB1 TT vs. PM+non-ABCB1 TT (CC/CT) : HR; 2.86, 95% CI; 1.09-7.57, p for interaction=0.15) as well as HR of PM+ABCB1 TT genotype to non-PM+non-ABCB1 TT genotype (CC/CT) were significantly increased (HR; 3.97, 95% CI; 1.71-9.21) compared with that of each CYP2C19 PM and ABCB1 TT genotype. This combined effect of CYP2C19 PM was not seen in polymorphism of other genes.
Conclusions In conclusion, when both ABCB1 and CYP2C19 are taken into account, we may predict 1-year MACCE better in clopidogrel on-treatment patients in real-world PCI cohort.
- © 2011 by American Heart Association, Inc.