據(jù)10月26日刊《美國(guó)醫(yī)學(xué)會(huì)雜志》（JAMA）上的一則研究披露,，帶有某些基因或與使用抗凝血藥物氯吡格雷有關(guān)的特別因子的患者，更可能在支架放置后不久在其冠狀動(dòng)脈支架內(nèi)出現(xiàn)凝血塊,。
根據(jù)文章的背景資料：“安放支架的經(jīng)皮冠狀動(dòng)脈介入治療（PCI,；人們用諸如球囊血管成形術(shù)或支架放置等術(shù)療來(lái)打開(kāi)狹窄的冠狀動(dòng)脈）已經(jīng)成為心肌血管重建術(shù)的治療標(biāo)準(zhǔn)，特別是在病人存在不穩(wěn)定性冠心病的情況下,。盡管使用雙重抗血小板治療（DAPT,；阿司匹林和氯吡格雷）可減少80%以上的PCI后的心血管事件，但確定性的支架血栓形成（血塊）仍然令人擔(dān)憂,。”支架血栓形成可以是一種致命的（死亡率可高達(dá)40%）且不可預(yù)知的PCI的并發(fā)癥,。大多數(shù)的支架血栓形成發(fā)生在支架放置后的第一個(gè)月，它們被定義為早期支架血栓形成,。
巴黎Pitie-Salpetriere 醫(yī)院的Guillaume Cayla, M.D., Ph.D.及其同事開(kāi)展了一項(xiàng)對(duì)與確定性早期支架血栓形成有關(guān)的臨床和遺傳因素的分析,。這項(xiàng)于2007年1月至2010年5月間在法國(guó)的10個(gè)中心內(nèi)開(kāi)展的研究包括了123名接受了PCI并有確定性早期支架血栓形成（發(fā)生在支架放置后30天內(nèi)）的患者和他們的DNA樣本，這些患者及DNA樣本與246名沒(méi)有發(fā)生支架血栓癥的對(duì)照者進(jìn)行了年齡和性別的匹配,。檢測(cè)的主要結(jié)果是對(duì)帶有23種遺傳變異者發(fā)生早期支架血栓的預(yù)測(cè)準(zhǔn)確性,。
研究人員進(jìn)行了多變量分析以確定哪些臨床、血管造影和遺傳變量獨(dú)立地與早期支架血栓形成的發(fā)生有關(guān)系,。在對(duì)15個(gè)不同基因內(nèi)的23個(gè)遺傳變異的調(diào)查中,，研究人員發(fā)現(xiàn)，3個(gè)與氯吡格雷代謝和血小板功能有關(guān)的基因型（CYP2C19,、 ABCB1和 ITGB3）是早期支架血栓形成的獨(dú)立風(fēng)險(xiǎn)因子,。文章的作者還發(fā)現(xiàn)了早期支架血栓形成的2個(gè)可能被更改的因子：氯吡格雷的負(fù)荷劑量及氯吡格雷與質(zhì)子泵抑制劑的相互作用。與處于最低三分位數(shù)中的患者相比，那些在應(yīng)用某種臨床與遺傳學(xué)組合模型中的處于最高三分位數(shù)（3組中的1組）中的患者發(fā)生早期支架血栓的風(fēng)險(xiǎn)會(huì)增加7倍,。
研究人員寫(xiě)道：“我們的研究增加了對(duì)接受氯吡格雷治療并有發(fā)生早期支架血栓形成風(fēng)險(xiǎn)患者的遺傳特征的理解,。”
“將遺傳因子與臨床因子相結(jié)合可改善支架血栓形成的風(fēng)險(xiǎn)度分層。但基于這種綜合性風(fēng)險(xiǎn)度分層而對(duì)治療進(jìn)行調(diào)整,，是否能改善接受了PCI的病人的預(yù)后還需要在將來(lái)在獨(dú)立群組研究中得到確認(rèn),。”（生物谷 Bioon.com）
doi:10.1001/jama.2011.1529
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Clinical, Angiographic, and Genetic Factors Associated With Early Coronary Stent Thrombosis
Cayla, Guillaume; Hulot, Jean-Sébastien; O’Connor, Stephen A.; Pathak, Atul; Scott, Stuart A.; Gruel, Yves; Silvain, Johanne; Vignalou, Jean-Baptiste; Huerre, Yves; de la Briolle, Axel; Allanic, Frédérick; Beygui, Farzin; Barthélémy, Olivier; Montalescot, Gilles; Collet, Jean-Philippe
Context Despite dual antiplatelet therapy, stent thrombosis remains a devastating and unpredictable complication of percutaneouscoronary 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 PCIwho 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 thrombosiswere 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 (adjustedOR, 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 clopidogrelloading doses (adjusted OR, 0.73; 95% CI, 0.57-0.93). The discriminative accuracy of the clinical-only model was similar tothat 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 ofthe 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 earlystent thrombosis. Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts.
