Abstract 18034: Clinical, Angiographic and Genetic Determinants of Early Coronary Stent Thrombosis: the ONASSIST Study

Abstract

OBJECTIVES: To perform a comprehensive analysis of all determinants of definite early stent thrombosis (ST) to identify the risk and the modifiable factors of early EST. Methods: Using a web-based case collection and reporting system, 123 patients with definite early ST on dual antiplatelet therapy were matched 2:1 according to age and gender with 246 controls. All patients were genotyped for 23 genetic variants involved in clopidogrel metabolism ( CYP2C19 , CYP2C9, CYP2B6, CYP3A5, POR, ABCB1, PON1 ), platelet receptor function ( P2Y12, ITGB3 ), and the coagulation and fibrinolytic system ( MTHFR , Factor V, Fibrinogen, Prothrombin, PAI1 and VKORC1 ). Results: CYP2C19*2 (OR und =2.53, 95% CI [1.61-3.97], p<0.0001) and ABCB1 TT3435 (OR und =2.01, 95% CI [1.22-3.30], p=0.006) carriers were more frequent among patients with EST than controls while CYP2C19*17 (OR und =0.53, 95% CI [0.31-0.88], p=0.01) and ITGB3 PlA2 (OR und =0.50, 95% CI [0.29-0.87], p=0.01) carriers were less frequent. Percutaneous coronary intervention in acute setting, complex lesions, impaired left ventricular function < 35%, high clopidogrel loading doses and use of proton pump inhibitor were non genetic independent correlates of early ST. The accuracy of the clinical model to discriminate between early ST and controls (AUC 0.72, 95% CI [0.66-0.77] did not differ significantly from the genetic model (AUC 0.68, 95% CI [0.62-0.73] (p=0.34), although combining both led to a significant improvement in the discriminatory power of the model (AUC 0.78, 95% CI [0.73-0.83], p=0.004). Among all independent predictors of early ST, the use of high clopidogrel loading doses (OR=0.73, 95% CI[0.57-0.94], p=0.01) and proton pump inhibitors (OR=2.19, 95% CI [1.28-3.72], p=0.004) were the only modifiable factors. Conclusion: In addition to established clinical and angiographic factors, three genes involved in clopidogrel metabolism and platelet receptor function (CYP2C19, ABCB1, ITGB3) significantly improved the ability to predict early ST. PPI use and clopidogrel dose were both independently correlated with the risk of early ST, suggesting that the final amount of active metabolite generated is a major factor of prevention.