Doggrell Sheila A
University of Queensland, School of Biomedical Sciences, Australia.
Expert Opin Pharmacother. 2004 Nov;5(11):2209-20. doi: 10.1517/14656566.5.11.2209.
The restenosis rate is lower with stent implantation than with balloon angioplasty. Nevertheless, even with the use of stenting, restenosis still occurs in approximately one-third of patients with diabetes, small coronary vessels, and long lesions. The two drugs commonly used in eluting stents are sirolimus and paclitaxel. Systemically administered sirolimus decreased vascular proliferation in animal models. After preliminary trials showing benefit with sirolimus-eluting stents in de novo coronary lesions, the large-scale SIRIUS (Sirolomus-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) trial was undertaken. SIRIUS showed that sirolimus reduced restenosis and target vessel revascularisation, compared to bare stents. These benefits were also apparent in the diabetic, and small- and long vessel subgroups. The RESEARCH (Rapamycin-eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry have established that sirolimus-eluting stents are superior to bare stents in practice. Thus, the benefits of sirolimus-eluting stents over bare stents have been clearly established, and sirolimus can be considered the benchmark eluting agent for the prevention of coronary artery restenosis. Animal studies with paclitaxel-eluting stents, mainly in endothelium denuded normal vessels, have shown that paclitaxel reduces restenosis in the short-term, and that this may be a delay, rather than a prevention of restenosis. In clinical trials, stents eluting the paclitaxel derivative 7-hexanolytaxol, or paclitaxel without a polymer, delay rather than prevent restenosis. Slowing the release of paclitaxel with a polymer base in the TAXUS (Taxol(trade mark) [paclitaxel]-eluting stent) series of clinical trials reduced the revascularisation rate at 12 and 18 months, indicating that polymer-based paclitaxel is effective for longer. The results of the REALITY trial comparing the sirolimus- and paclitaxel-eluting stents in diabetics and other high-risk patients are eagerly awaited.
支架植入后的再狭窄率低于球囊血管成形术。然而,即使使用支架置入术,糖尿病、冠状动脉细小及病变较长的患者中仍约有三分之一会发生再狭窄。洗脱支架中常用的两种药物是西罗莫司和紫杉醇。全身给药的西罗莫司可降低动物模型中的血管增殖。在初步试验显示西罗莫司洗脱支架对初发冠状动脉病变有益后,开展了大规模的SIRIUS(西罗莫司涂层Bx Velocity球囊扩张支架治疗初发冠状动脉病变患者)试验。SIRIUS试验表明,与裸支架相比,西罗莫司可降低再狭窄率和靶血管血运重建率。这些益处在糖尿病患者以及血管细小和病变较长的亚组中也很明显。RESEARCH(鹿特丹心脏病医院对雷帕霉素洗脱支架的评估)注册研究证实,在实际应用中,西罗莫司洗脱支架优于裸支架。因此,西罗莫司洗脱支架相对于裸支架的益处已得到明确证实,西罗莫司可被视为预防冠状动脉再狭窄的基准洗脱剂。关于紫杉醇洗脱支架的动物研究主要在剥脱内皮的正常血管中进行,结果显示紫杉醇可在短期内降低再狭窄率,这可能只是延迟而非预防再狭窄。在临床试验中,洗脱紫杉醇衍生物7-己醇紫杉醇或不含聚合物的紫杉醇的支架只能延迟而非预防再狭窄。在TAXUS(紫杉醇洗脱支架)系列临床试验中,使用聚合物基质减缓紫杉醇的释放可降低12个月和18个月时的血运重建率,这表明基于聚合物的紫杉醇在更长时间内有效。人们急切期待着比较糖尿病患者和其他高危患者中西罗莫司洗脱支架与紫杉醇洗脱支架的REALITY试验结果。