A combined clinical and genetic model significantly improved the predictive accuracy for early stent thrombosis compared with a clinical-only model (AUC 0.78 vs 0.73; P=.004).
Case-Control (n=369)
Yes
Do specific clinical, angiographic, and genetic factors accurately predict early stent thrombosis in patients undergoing PCI?
Combining genetic testing (CYP2C19, ABCB1, ITGB3) with clinical and angiographic factors significantly improves the prediction of early stent thrombosis after PCI compared to clinical factors alone.
Odds Ratio: 1.99 (95% CI 1.47–2.69)
CONTEXT: Despite dual antiplatelet therapy, stent thrombosis remains a devastating and unpredictable complication of percutaneous coronary intervention (PCI). OBJECTIVE: To perform a sequential analysis of clinical and genetic factors associated with definite early stent thrombosis. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 10 centers in France between January 2007 and May 2010 among 123 patients undergoing PCI who had definite early stent thrombosis and DNA samples available, matched on age and sex with 246 stent thrombosis-free controls. MAIN OUTCOME MEASURE: Accuracy of early stent thrombosis prediction by 23 genetic variants. RESULTS: Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (adjusted odds ratio OR, 1.99; 95% CI, 1.47-2.69), ABCB1 3435 TT genotype (adjusted OR, 2.16; 95% CI, 1.21-3.88), and ITGB3 PLA2 carriage (adjusted OR, 0.52; 95% CI, 0.28-0.95). Nongenetic independent correlates were acuteness of PCI (adjusted OR, 3.05; 95% CI, 1.54-6.07), complex lesions (American College of Cardiology/American Heart Association type C) (adjusted OR, 2.33; 95% CI, 1.40-3.89), left ventricular function less than 40% (adjusted OR, 2.25; 95% CI, 1.09-4.70), diabetes mellitus (adjusted OR, 1.82; 95% CI, 1.02-3.24), use of proton pump inhibitors (adjusted OR, 2.19; 95% CI, 1.29-3.75), and higher clopidogrel loading doses (adjusted OR, 0.73; 95% CI, 0.57-0.93). The discriminative accuracy of the clinical-only model was similar to that of a genetic-only model (area under the curve, 0.73 95% CI, 0.67-0.78 vs 0.68 95% CI, 0.62-0.74, respectively; P = .34). A combined clinical and genetic model led to a statistically significant increase in the discriminatory power of the model compared with the clinical-only model (area under the curve, 0.78 95% CI, 0.73-0.83 vs 0.73 95% CI, 0.67-0.78; P = .004). CONCLUSIONS: This case-control study identified 3 genes (CYP2C19, ABCB1, and ITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with early stent thrombosis. Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts.
Cayla et al. (Tue,) conducted a case-control in early coronary stent thrombosis (n=369). Genetic variants (including CYP2C19, ABCB1, ITGB3) and clinical factors vs. Stent thrombosis-free controls was evaluated on Accuracy of early stent thrombosis prediction by 23 genetic variants (OR 1.99, 95% CI 1.47-2.69). A combined clinical and genetic model significantly improved the predictive accuracy for early stent thrombosis compared with a clinical-only model (AUC 0.78 vs 0.73; P=.004).
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