药物洗脱支架（DES）内血栓一直是病理学家和临床医生研究的焦点。

　　在2007TCT会议有关DES置入后支架内血栓（ST）发病机制的研讨会上，Virmani医生（CVPath Institute in Gaithersburg）和Camenzind（University of Geneva）医生就置入DES的患者ST发生的病理机制、临床特征及其发生率等问题展开讨论。

　　CVPath DES注册研究发现，2005年以来，患者置入DES后早发和晚发ST发生率呈下降趋势。2005年早发ST（<30天）和晚发ST（>30天）发生率分别高达23%和26%，而现在则分别降至7%和14%。

　　Virmani医生认为抗血小板药物的合理使用，支架工艺的改进和置入技术的提高是ST发生率降低的原因。不过，置入DES的患者，其ST发生率仍然高于置入金属裸支架（BMS）的患者。Camenzind医生说，MILAN 和ERACI III注册研究中发生晚期ST患者的死亡率分别为45%和44.4%。他同时指出，造影显示晚期ST（30天）的年累积发生率平均为0.6%。

　　ST发生的预测因素

　　根据Virmani教授的报道，内皮化不全是ST发生的可靠的预测因子。既往研究发现，经过18个月的随访，置入DES患者内皮化不全的晚期ST发生率明显高于置入BMS的患者（18月时，55.8%的DES支架表面内皮化，而BMS为89.8%，P＝0.0001）。置入DES患者的内膜化面积小于置入BMS的患者，说明DES对延缓支架内再狭窄有利，但DES患者的纤维蛋白积分却明显高于BMS患者。（如图）

　　Virmani指出，支架丝被内皮覆盖是支架内皮化的一个非常准确的标志，它与ST发生的病理过程相关，是ST发生的一个预测因素。每个节段未被内皮覆盖面积占整个支架丝面积的比值（RUTSS）超过30%时，发生晚发ST的优势比（OR）为9.0（95% CI, 3.5-22）。最近一项研究(Circulation 2007;115:2435-41)发现，支架内纤维蛋白聚集和炎症积分也是ST发生的病理学预测因子。

　　ST病因

　　Virmani说，AMI患者是否置入DES依然存有争议。CVPath 注册研究显示，AMI患者较未发生AMI的患者拥有更多的ST预测因子，包括更多的支架丝纤维蛋白(67.2% vs. 41.8%; P = 0.02)、支架丝炎症反应（54.7% vs. 17.8%; P =0 .03）和未覆盖的支架丝面积(33.6% vs. 23.8%; P =0.02)。Virmani认为AMI患者较易发生ST是由于支架内斑块破裂处存在未被代谢完的药物的可能性更大。

　　不同DES应当区别对待

　　Camenzind强调说，不同种类DES的ST发生率并不都一样，每种DES都应分别分析。由于目前大多数随机临床试验主要使用的是Cypher支架（39个随机试验）和Taxus支架（29个随机试验），因此，大部分试验结果来自于其中一种或两种支架的随机试验。对4项随机试验（包括RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS）荟萃分析发现，置入Cypher支架死亡率＋Q波MI发生率为6.3%（n＝878），明显高于置入BMS的患者（n＝870，3.9%，P＝0.03）。

　　（阜外心血管病医院　丁立刚　高立建　编译）

Pathology, Prevalence, and Risk Factors of Stent Thrombosis After DES

Pathologist and clinician weigh in on persistent risks of DES.

In a session investigating the pathogenesis of stent thrombosis after DES implantation, Renu Virmani, MD, of the CVPath Institute in Gaithersburg, Md., and Edoardo Camenzind, MD, of the University of Geneva, examined the pathological correlates and clinical profiles of ST risk and occurrence in DES patients.

Since 2005, the rates of early and late stent thrombosis in DES patients have decreased, from a high of 23% for early ST (<30 days) and 26% for late ST (>30 days) in 2005 to the more current rate of 7% and 14% for early and late ST, respectively, according to the CVPath DES Registry.

Virmani attributes this to possible improvements in antiplatelet therapy, stent technology, and implantation procedures. However, the risk remains higher for DES patients than for bare-metal stent patients. Camenzind referred to the MILAN and ERACI III registries, which showed mortality rates of 45% and 44.4%, respectively, in cases of late ST. He also cited data showing the cumulative incidence of late angiographic ST (.30 days) is, on average, 0.6% per year.

Predictors of ST

Lack of endothelialization is a “good predictor of ST,” and DES patients in previous studies have shown significantly less endothelialization after 18-month follow-up than bare-metal stent patients (55.8% of DES struts were endothelialized after 18 months compared with 89.8% of bare-metal stent struts; P = .0001). Neointimal area was smaller in DES patients, indicating DES usefulness in retarding restenosis, but fibrin score was significantly higher for DES patients, according to Virmani (Figure).

Strut coverage as a marker of endothelialization shows significant accuracy, and it is a pathological correlate that should be recognized as a predictor of ST, Virmani said. The odds ratio for late ST in lesions having a ratio of uncovered-tototal stent struts per section (RUTSS) greater than 30% is 9.0 (95% CI, 3.5-22). Other pathological predictors of ST development include fibrin accumulation on the stent, as well as inflammation score, according to a recent study she cited (Circulation 2007;115:2435-41).

Causes of ST

Particularly problematic, according to Virmani, is implanting DES in the setting of AMI. Patients with AMI showed significantly higher rates of predictors for ST compared with non-AMI patients, including strut fibrin (67.2% vs. 41.8%; P = .02), strut inflammation (54.7% vs. 17.8%; P = .03) and uncovered struts (33.6% vs. 23.8%; P = .02), according to data from the CVPath registry. Virmani attributes this risk for ST in AMI patients to the fact that in a ruptured plaque site, there is a higher likelihood of unmetabolized drug being present.

DES must be evaluated separately

Camenzind emphasized that not all DES are the same, and each one must be evaluated separately. The Cypher (Cordis, Johnson & Johnson) and Taxus (Boston Scientific) stents have been subjected to the most randomized trials (39 and 29, respectively), so most results today refer to one or both of them. In a meta-analysis of 4 randomized trials (RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS), Camenzind et al found a 6.3% rate of mortality or Q-wave MI among Cypher patients (n = 878), significantly higher than the rate found among bare-metal stent patients (n = 870, 3.9%, P = .03).