Clinical, Angiographic, and Genetic Factors Associated With Early Coronary Stent Thrombosis
Clinical, Angiographic, and Genetic Factors Associated With Early Coronary Stent Thrombosis
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DOI：
10.1001/jama.2011.1529
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发表时间：
2011-10-26
影响因子：
120.7
通讯作者：
Collet, Jean-Philippe
中科院分区：
文献类型：
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作者：
Cayla, Guillaume;Hulot, Jean-Sebastien;Collet, Jean-Philippe
背景尽管双重抗血小板治疗，支架血栓形成仍然是经皮冠状动脉介入治疗（PCI）的一个毁灭性和不可预测的并发症。目的对与明确的早期支架血栓形成相关的临床和遗传因素进行连续分析。参与者案例-2007年1月至2010年5月在法国10家中心进行的对照研究，纳入了123例接受PCI的患者，这些患者有明确的早期支架内血栓形成，结果在15个不同基因的23个基因变异中，CYP 2C 19代谢状态是早期支架血栓形成的重要决定因素，CYP 2C 19代谢状态是早期支架血栓形成的重要决定因素，CYP 2C 19代谢状态是早期支架血栓形成的重要决定因素（调整的比值比[OR]，1.99; 95%CI，1.47-2.69），ABCB 1 3435 TT基因型（调整的OR，2.16; 95%CI，1.21-3.88），和ITGB 3 PLA 2携带（调整的OR，0.52; 95%CI，0.28-0.95）。非遗传独立相关因素为PCI的急性程度（校正OR，3.05; 95% CI，1.54-6.07），复杂病变（美国心脏病学会/美国心脏协会C型）（校正OR，2.33; 95% CI，1.40-3.89），左心室功能低于40%（校正OR，2.25; 95% CI，1.09-4.70），糖尿病（校正OR，1.82; 95% CI，1.02-3.24），使用质子泵抑制剂（调整后OR，2.19; 95% CI，1.29-3.75）和较高的氯吡格雷负荷剂量（调整后OR，0.73; 95% CI，0.57-0.93）。仅临床模型的判别准确性与仅遗传模型相似（曲线下面积分别为0.73 [95%CI，0.67-0.78] vs 0.68 [95%CI，0.62-0.74]; P= 0.34）。与仅临床模型相比，结合临床和遗传模型导致模型的区分能力在统计学上显著增加（曲线下面积，0.78 [95% CI，0.73-0.83] vs 0.73 [95% CI，0.67-0.78];结论：本病例对照研究确定了3个基因（CYP 2C 19、ABCB 1和ITGB 3）和2个氯吡格雷相关因素（负荷剂量和质子泵抑制剂）与早期支架内血栓形成独立相关。未来的研究需要验证这些危险因素在前瞻性队列中的预后准确性。美国医学会杂志2011;306（16）：1765-1774
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. JAMA. 2011;306(16):1765-1774