如图一所示，对38份随机临床研究的荟萃分析显示，裸支架的TLR率比DES支架更高。这些研究包括雷帕霉素vs裸支架，紫杉醇支架vs裸支架，以及雷帕霉素vs紫杉醇支架。

在雷帕霉素涂层支架的一份注册研究中，Serruys及其同事们报告称裸支架的5年期TVR率为19.6%，而雷帕霉素支架仅为12.9%。

另一些临床研究则关注累积的TLR。累积TLR的5年期数据在裸支架组中为18%。

动物模型

在猪的模型中，接受雷帕霉素治疗和裸支架治疗的个体，其损伤和炎症评分从30天到180天的范围内开始升高。
采用雷帕霉素释放支架治疗的血管节段的增生细胞核抗原（PCNA）测定值在90天开始抬高，损伤和炎症指数在30天到180天之间抬高。在90天时，雷帕霉素在血管壁中的含量明显升高。PCNA在30天时的增加在附膜支架组中比裸支架组更明显。同样，紫杉醇支架在动物模型中有着类似的结果。

（来源：www.tctmd.com）

• Discrepancies between animal and human models attributed to several factors.

By TCT Daily Staff

Sirolimus-eluting and paclitaxel-eluting stents failed to reduce neointimal proliferation at 90 to 180 days in animal models. In humans, however, results were much better, said Patrick W. Serruys, MD, PhD.

Serruys, from the Thoraxcenter, Erasmus MC in Rotterdam, The Netherlands, said several randomized trials and registries comparing DES and bare-metal stents "revealed a significant and persistent reduction in clinical angiographic restenosis up to 36 to 60 months."

The discrepancy between animal and human models could be attributed to differences in species response to sirolimus and paclitaxel and physiological stimuli for neointimal formation, he said. "Delayed neointimal growth may also be due to other mechanisms such as shear stress, adaptive neointimal thickening, and de novo atherosclerosis."

Data in humans

A network meta-analysis of 38 randomized controlled trials in humans comparing sirolimus-eluting vs. bare-metal stents, paclitaxel-eluting vs. bare-metal stents, and sirolimus-eluting vs. paclitaxel-eluting stents found a higher incidence of TLR with bare-metal stents than with DES (see Figure 1).

In the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry, Serruys and colleagues reported a five-year TVR rate of 19.6% for bare-metal stents and 12.9% for sirolimus-eluting stents.

Several clinical trials have looked at increases in cumulative TLR over time. The cumulative rate of TLR with bare-metal stents among these trials was 18% at five years (see Figure 2).

Animal studies

In porcine models, injury and inflammation scores increased between 30 and 180 days for those treated with sirolimus-eluting stents vs. animals treated with bare-metal stents.

The vascular segments treated with sirolimus-eluting stents demonstrated elevated expression of proliferating cell nuclear antigen (PCNA) levels at 90 days in comparison with bare-metal stents, despite up-regulation of p27kip1. Injury and inflammation scores increased between 30 and 180 days for the sirolimus-eluting stent group compared with the bare-metal stent group.

At 90 days, sirolimus was present in the arterial tissue with an increased level of p27kip1. PCNA was more expressed in the vessel wall after 30 days in the sirolimus-eluting stent group compared with the bare-metal stent group. Similarly, the paclitaxel-eluting stent also showed late catch-up in the animal model.

Disclosures:
• Dr. Serruys reports no relevant conflicts of interest.