Paclitaxel-Coated Zilver PTX Drug-Eluting Stent Treatment Does Not Result in Increased Long-Term All-Cause Mortality Compared to Uncoated Devices.
与未涂层器械相比，紫杉醇涂层 Zilver PTX 药物洗脱支架治疗不会导致长期全因死亡率增加。
- 作者列表："Dake MD","Ansel GM","Bosiers M","Holden A","Iida O","Jaff MR","Lottes AE","O'Leary EE","Saunders AT","Schermerhorn M","Yokoi H","Zeller T
PURPOSE:Patient-level data from two large studies of the Zilver PTX drug-eluting stent (DES) with long-term follow-up and concurrent non-drug comparator groups were analyzed to determine whether there was an increased mortality risk due to paclitaxel.,METHODS:Data from the Zilver PTX randomized controlled trial (RCT) and Zilver PTX and bare metal stent (BMS) Japan post-market surveillance studies were analyzed. Five-year follow-up is complete in both DES studies; follow-up for the BMS study was limited to 3 years and is complete. Kaplan-Meier analyses assessed mortality. A Cox proportional hazards model identified significant factors related to mortality.,RESULTS:In the RCT, there were 336 patients treated with the DES and 143 patients treated with percutaneous transluminal angioplasty (PTA) or BMS. In Japan, there were 904 DES patients and 190 BMS patients. There was no difference in all-cause mortality for the DES compared to PTA/BMS in the RCT (19.1% DES versus 17.1% PTA/BMS through 5 years, p = 0.60) or Japan (15.8% DES versus 15.3% BMS through 3 years, p = 0.89). Cox proportional hazard models revealed that age, tissue loss, and congestive heart failure were significantly associated with mortality in the RCT, and critical limb ischemia, age, renal failure, and gender were significantly associated with mortality in Japan (all p < 0.05). Neither treatment with Zilver PTX (p = 0.46 RCT, p = 0.49 Japan) nor paclitaxel dose (p = 0.86 RCT, p = 0.07 Japan) was associated with mortality.,CONCLUSION:Analyses of the Zilver PTX patient-level data demonstrated no increase in long-term all-cause mortality.,LEVEL OF EVIDENCE:Zilver PTX RCT: Level 1, randomized controlled trial; Japan PMS studies: Level 3, post-market surveillance study.
目的: 来自 Zilver PTX 药物洗脱支架 (DES) 的两项大型研究的患者水平数据对长期随访和同期非药物比较组进行分析，以确定紫杉醇是否增加死亡风险。,方法: 数据来自 Zilver PTX 随机对照试验 (RCT) 和 Zilver PTX 和裸金属支架 (BMS)日本上市后监测研究进行了分析。两项 DES 研究的 5 年随访均完成; BMS 研究的随访仅限于 3 年，且已完成。Kaplan-Meier 分析评估死亡率。Cox 比例风险模型确定了与死亡率相关的显著因素。,结果: 在 RCT 中，336 例患者接受了 DES 治疗，143 例患者接受了经皮腔内血管成形术 (PTA) 或 BMS 治疗。在日本，有 904 例 DES 患者和 190 例 BMS 患者。在 RCT 中，与 PTA/BMS 相比，DES 的全因死亡率没有差异 (5 年间 19.1% DES 与 17.1% PTA/BMS，p = 0.60) 或日本 (15.8% DES 与 15.3% BMS 通过 3 年，p = 0.89)。Cox 比例风险模型显示，年龄、组织丢失和充血性心力衰竭与 RCT 死亡率、严重肢体缺血、年龄、肾功能衰竭显著相关。在日本，性别与死亡率显著相关 (均 p <0.05)。Zilver PTX 治疗 (p = 0.46 RCT，p = 0.49 日本) 和紫杉醇剂量 (p = 0.86 RCT，p = 0.07 日本) 均与死亡率无关。结论: 对 Zilver PTX 患者水平数据的分析显示长期全因死亡率没有增加。,证据级别: Zilver PTX RCT: 1 级，随机对照试验; 日本 PMS 研究: 3 级,上市后监测研究。
METHODS:Aims : We sought to investigate the thrombogenicity of different DES and BMS in an in vitro system of stent perfusion. Material and Methods: The experimental model consisted of a peristaltic pump connected to 4 parallel silicone tubes in which different stents were deployed. Blood was drawn from healthy volunteers and the amount of stent surfaced -induced thrombus deposition was determined using 125 I -fibrinogen. Results: Compared to Resolute, Biomatrix and Vision, Xience was associated with the lowest amount of stent surface -induced thrombus formation, with a significant difference compared to Vision (125 I -fibrinogen median value deposition [IQ range]: 50 ng [25 -98] versus 560 ng [320 - 1,520], respectively, p<0.05), but not to other DES. In the second set of experiments Fluoropolymer -coated BMS not eluting drug was associated with a significant 3 -fold reduction in 125 I -fibrinogen deposition (245 ng [80 -300]) compared to Vision (625 ng [320 -760], p<0.05), but a 7 -fold increase compared to Xience (35 ng [20 -60], p<0.05). Finally Xience was associated with a significantly greater absorption of albumin compared to BMS. Conclusions: In an in vitro system of stent perfusion, Xience was associated with the lowest amount of stent surface -induced thrombus formation compared with Resolute, Biomatrix and Vision, with a noted synergistic effect between the fluoropolymer and the drug.
METHODS::Fibronectin-splice variant containing extra domain A (Fn-EDA) is associated with smooth muscle cells (SMCs) following vascular injury. The role of SMC-derived Fn-EDA in SMC phenotypic switching or its implication in neointimal hyperplasia remains unclear. Herein, using human coronary artery sections with a bare metal stent, we demonstrate the expression of Fn-EDA in the vicinity of SMC-rich neointima and peri-strut areas. In mice, Fn-EDA colocalizes with SMCs in the neointima of injured carotid arteries and promotes neointima formation in the comorbid condition of hyperlipidemia by potentiating SMC proliferation and migration. No sex-based differences were observed. Mechanistic studies suggested that Fn-EDA mediates integrin- and TLR4-dependent proliferation and migration through activation of FAK/Src and Akt1/mTOR signaling, respectively. Specific deletion of Fn-EDA in SMCs, but not in endothelial cells, reduced intimal hyperplasia and suppressed the SMC synthetic phenotype concomitant with decreased Akt1/mTOR signaling. Targeting Fn-EDA in human aortic SMCs suppressed the synthetic phenotype and downregulated Akt1/mTOR signaling. These results reveal that SMC-derived Fn-EDA potentiates phenotypic switching in human and mouse aortic SMCs and neointimal hyperplasia in the mouse. We suggest that targeting Fn-EDA could be explored as a potential therapeutic strategy to reduce neointimal hyperplasia.
METHODS:OBJECTIVE:The goal of this study was to determine the impact of late-acquired stent malapposition (LASM) on long-term clinical outcomes in patients treated with coronary stent implantation. Approach and Results: We investigated major adverse cardiac event during 10 years after 6-month intravascular ultrasound examination using our previous studies database. A total of 732 patients treated with bare-metal stent (54 LASM versus 678 non-LASM) and 529 patients treated with first-generation drug-eluting stent (82 LASM versus 447 non-LASM), who did not have clinical event or censoring at the time of follow-up intravascular ultrasound, were included for the present analysis. major adverse cardiac event was defined as the composite of cardiac death, target vessel-related myocardial infarction, target lesion revascularization and stent thrombosis. Multivariable adjustment and inverse probability weight were performed to consider baseline differences. After multivariable adjustment, LASM was related to a greater risk of major adverse cardiac event (hazard ratio, 1.666 [95% CI, 1.041-2.665]; P=0.0333) and very-late stent thrombosis (hazard ratio, 3.529 [95% CI, 1.153-10.798]; P=0.0271) than non-LASM in patients treated with first-generation drug-eluting stent, but not in those treated with bare-metal stent. Results were consistent after inverse probability weight. Among patients with LASM of first-generation drug-eluting stent, no late stent thrombosis occurred in patients who continued to receive dual antiplatelet therapy. CONCLUSIONS:The relationship between LASM and major adverse cardiac event might depend on the type of implanted stents during the long-term follow-up, highlighting the clinical significance of polymers and drugs in drug-eluting stent system.