Grube E, Gerckens U, Müller R, Büllesfeld L
Heart-Center Siegburg Ringstrasse 49 53721 Siegburg, Germany.
Z Kardiol. 2002;91 Suppl 3:44-8. doi: 10.1007/s00392-002-1309-x.
Local delivery of immunosuppressive or antiproliferative agents using a drug-eluting stent is a new technology meant to inhibit in-stent restenosis providing both a biological and mechanical solution and has recently emerged as a very promising approach. Up to now several agents have been in use: Paclitaxel, Rapamycin, Actinomycin D or Tacrolimus. Evaluating these drugs regarding their release kinetics, effective dosage, safety in clinical practice and benefit, several studies have been published or are still ongoing: SCORE (Paclitaxel-derivative), TAXUS I, II, III, IV (Paclitaxel), ELUTE, ASPECT (Paclitaxel), RAVEL, SIRIUS (Sirolimus), ACTION (Actinomycin), EVIDENT, PRESENT (Tacrolimus). Paclitaxel was the first stent-based antiproliferative agent under clinical investigation providing profound inhibition of neointimal thickening, depending on delivery duration and drug dosage. The randomized multicenter SCORE trail (Quanam stent, Paclitaxel coated) enrolled 266 patients at 17 sites. At 6 month follow-up, a drop of 83% in stent restenosis using the drug-eluting stent could be achieved (6.4% drug-eluting stent vs. 36.9% control group) attributable to a remarkable decrease in intimal proliferation. Unfortunately, due to both frequent stent thrombosis and side-branch occlusions the reported 30-day MACE rate was 10.2%. The randomized TAXUS I safety trail (NIRx, Paclitaxel coated) also demonstrated beneficial reduction of restenotic lesions at 6-month FU (0% vs. 11%) but, this time, associated with the absence of thrombotic events presumably due to the lower drug dosage. The ongoing TAXUS II, III and IV trails are aimed at providing additional insight regarding the efficacy of the TAXUS Paclitaxel-eluting stent. Both the RAVEL and the SIRIUS trial have been conducted to evaluate a Sirolimus-coated stent (Bx VELOCITY stent). From the results available, the beneficial findings regarding reduction of renarrowing using a drug-eluting stent have been confirmed without any adverse effects. Although parameters like drug toxicity, optimal drug dosage or delayed endothelial healing need to be further evaluated, summarizing the today's clinical experience the strategy of drug-coated stents promises a striking benefit in interventional treatment of coronary lesions.
使用药物洗脱支架局部递送免疫抑制或抗增殖药物是一项旨在抑制支架内再狭窄的新技术，它提供了一种生物学和机械学的解决方案，并且最近已成为一种非常有前景的方法。到目前为止，已有几种药物在使用：紫杉醇、雷帕霉素、放线菌素D或他克莫司。关于这些药物的释放动力学、有效剂量、临床实践中的安全性和益处，已经发表了几项研究或仍在进行中：SCORE（紫杉醇衍生物）、TAXUS I、II、III、IV（紫杉醇）、ELUTE、ASPECT（紫杉醇）、RAVEL、SIRIUS（西罗莫司）、ACTION（放线菌素）、EVIDENT、PRESENT（他克莫司）。紫杉醇是第一个接受临床研究的基于支架的抗增殖药物，它能根据递送持续时间和药物剂量对新生内膜增厚产生显著抑制作用。随机多中心SCORE试验（Quanam支架，涂有紫杉醇）在17个地点招募了266名患者。在6个月的随访中，使用药物洗脱支架可使支架再狭窄率下降83%（药物洗脱支架为6.4%，对照组为36.9%），这归因于内膜增殖的显著减少。不幸的是，由于频繁的支架血栓形成和分支闭塞，报告的30天主要不良心血管事件（MACE）发生率为10.2%。随机TAXUS I安全性试验（NIRx，涂有紫杉醇）在6个月随访时也显示出对再狭窄病变有有益的减少（0%对11%），但这次没有血栓形成事件，可能是由于药物剂量较低。正在进行的TAXUS II、III和IV试验旨在进一步深入了解TAXUS紫杉醇洗脱支架的疗效。RAVEL和SIRIUS试验都已进行，以评估西罗莫司涂层支架（Bx VELOCITY支架）。从现有结果来看，使用药物洗脱支架减少再狭窄的有益发现得到了证实，且没有任何不良反应。尽管药物毒性、最佳药物剂量或内皮愈合延迟等参数需要进一步评估，但总结当今的临床经验，药物涂层支架策略在冠状动脉病变的介入治疗中有望带来显著益处。
