Moses Jeffrey W, Kipshidze Nicholas, Leon Martin B
Lenox Hill Heart and Vascular Institute of New York and Cardiovascular Research Foundation, New York, New York 10021, USA.
Am J Cardiovasc Drugs. 2002;2(3):163-72. doi: 10.2165/00129784-200202030-00004.
Coronary stent implantation has become a well established therapy in the management of coronary artery disease (CAD). Although the Stent Restenosis Study (STRESS) and Belgium-Netherlands Stent (BENESTENT) trials demonstrated convincingly that stenting is superior to percutaneous transluminal coronary angioplasty with respect to restenosis in de novo lesions, there is, however, still a high incidence (10 to 50%) of restenosis following stent implantation. Improvements in stent design and implantation techniques resulted in an increase in the use of coronary stents and today, in most centers in the US and Europe, stenting has become the predominant form of nonsurgical revascularization accounting for about 80% of all percutaneous coronary intervention procedures. Coronary stents provide luminal scaffolding that virtually eliminates elastic recoil and remodelling. Stents, however, do not decrease neointimal hyperplasia and in fact lead to an increase in the proliferative comportment of restenosis. Agents that inhibit cell-cycle progression indirectly have also been tested as inhibitors of vascular proliferation. When coated onto stents, sirolimus, a macrolide antibiotic with immunosuppressive properties, and paclitaxel and dactinomycin, both chemotherapeutic agents, induced cell-cycle arrest in smooth muscle cells (SMC) and inhibited neointimal formation in animal models. Preliminary clinical studies with drug-eluting stents produced dramatic results eliminating restenosis in large and mid-size arteries. Quantitative coronary angiography and intravascular ultrasound demonstrated virtually complete inhibition of tissue growth at 6 and 12 months after sirolimus-eluting stent implantation. Results are also very encouraging with paclitaxel-coated stents. However, it needs to be proven that current drug-eluting stents will produce similar results in 'real life' interventional practice (long lesions, lesions in small vessels, in vein grafts, chronic total occlusions, and bifurcated and ostial lesions). The ongoing randomized, double-blind sirolimus-coated Bx Velocity trade mark balloon expandable stent in the treatment of patients with de novo coronary artery lesions (SIRIUS) trial may answer some of these concerns. With further improvements, including the expansion of drug-loading capacity, double coatings and coatings with programmable pharmacokinetic capacity using advances in nanotechnology (which may allow for more precise and controlled release of less toxic and improved molecules), we think that in the next few years the practice of interventional cardiology may undergo major changes. A new era of dramatic improvements in the treatment of CAD may have dawned. The prospect of approval of this technology should herald a host of clinical trials to revisit basic assumptions about the place of coronary stenting in the contemporary care of obstructive (and nonobstructive) CAD.
冠状动脉支架植入术已成为治疗冠状动脉疾病（CAD）的一种成熟疗法。尽管支架再狭窄研究（STRESS）和比利时-荷兰支架（BENESTENT）试验令人信服地表明，在治疗初发病变时，支架植入术在预防再狭窄方面优于经皮腔内冠状动脉成形术，然而，支架植入术后仍有较高的再狭窄发生率（10%至50%）。支架设计和植入技术的改进导致冠状动脉支架的使用增加，如今，在美国和欧洲的大多数中心，支架植入术已成为非手术血管重建的主要方式，约占所有经皮冠状动脉介入治疗手术的80%。冠状动脉支架提供管腔支架，几乎消除了弹性回缩和重塑。然而，支架并不能减少新生内膜增生，实际上还会导致再狭窄增殖成分增加。间接抑制细胞周期进程的药物也已作为血管增殖抑制剂进行了测试。西罗莫司（一种具有免疫抑制特性的大环内酯类抗生素）、紫杉醇和放线菌素D（均为化疗药物）涂覆在支架上时，可诱导平滑肌细胞（SMC）的细胞周期停滞，并在动物模型中抑制新生内膜形成。药物洗脱支架的初步临床研究取得了显著成果，消除了大中动脉的再狭窄。定量冠状动脉造影和血管内超声显示，西罗莫司洗脱支架植入后6个月和12个月时，组织生长几乎完全受到抑制。紫杉醇涂层支架的结果也非常令人鼓舞。然而，需要证明目前的药物洗脱支架在“实际”介入治疗中（长病变、小血管病变、静脉桥血管病变、慢性完全闭塞病变以及分叉病变和开口病变）能产生类似的效果。正在进行的随机、双盲西罗莫司涂层Bx Velocity商标球囊扩张支架治疗初发冠状动脉病变患者（SIRIUS）试验可能会回答其中一些问题。随着进一步改进，包括扩大载药量、双层涂层以及利用纳米技术进展实现具有可编程药代动力学能力的涂层（这可能允许更精确和可控地释放毒性更小且性能更佳的分子），我们认为在未来几年，介入心脏病学的实践可能会发生重大变化。CAD治疗取得显著改善的新时代可能已经来临。这项技术获批的前景应该会引发一系列临床试验，以重新审视关于冠状动脉支架在当代阻塞性（和非阻塞性）CAD治疗中地位的基本假设。
