Abstract 14879: Impact of Vascular Function and Genotyping on Platelet Activation and Cardiovascular Outcome in Patients After Percutaneous Coronary Intervention Receiving Clopidogrel: Two Pieces of the Puzzle of Clopidogrel Resistance
Background: Individual platelet response to antiplatelet therapy depends on genetic, cellular and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet response to antiplatelet treatment. We evaluated the impact of vascular function, CYP2C19*2 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) receiving clopidogrel treatment.
Methods: We enrolled 408 patients with stable coronary artery disease (CAD) receiving clopidogrel (75mg/d), one month after PCI. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. High on treatment platelet reactivity was evaluated using VerifyNow Assay. VerifyNow reports its results in P2Y12 reaction units (PRU) and the diagnostic cut-off value is 230 PRU. 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 mean time of 14 months.
Results: Subjects with high on treatment platelet reactivity and PRU>230 had significantly increased PWV (p=0.001) and AIx (p=0.04). In the total study population, 37% were carriers of at least one CYP2C19*2 reduced-function allele and 53% were carriers of at least one C34T reduced-function allele. Although the rate of occurrence of primary end point differ significantly between carriers and non carriers of CYP2C19*2 (p=0.03), C34T polymorphism had no impact on cardiovascular outcome (p=0.17). Interestingly, carriers of two CYP2C19*2 reduced-function allele had significantly increased PRU (p=0.007). Though, PRU did not differ between carriers and non-carriers of the C34T-allele (p=0.47).
Conclusions: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms, on platelet reactivity and cardiovascular outcome in CAD patients after PCI receiving clopidogrel treatment. Moreover, increased arterial stiffness is associated with clopidogrel resistance in patients after PCI, highlighting another clinical factor implicated in individual platelet response to antiplatelet therapy.
- © 2013 by American Heart Association, Inc.