[TCT2008]ISAR-TEST 2试验显示：“双支架”疗效与Cypher相当，优于Endeavor

      2008年10月16日TCT周四的ISAR-TEST 2试验显示：无聚合物的普罗布考和西罗莫司双支架与永久聚合物Cypher支架在再狭窄和节段内管腔丢失率相当，都优于Endeavor支架。

      “普罗布考是一种非常有效的亲脂性抗氧化剂，”该试验的研究者Robert A. Byrne说，“并且它能减少再狭窄，这一点在动物模型和临床试验中都已经得到证实。”

      ISAR-TEST 2试验随机选取单支冠脉病变患者1,007例，接受双支架、Cypher支架或者Endeavor支架。在主要研究终点——节段内造影再狭窄和因缺血而驱使的TLR方面，双支架组和Cypher组类似，但是Endeavor组却表现得差强人意。在晚期管腔丢失率上，双支架组和Cypher组类似，0.23 mm vs. 0.26 mm; P=0.78，明显优于Endeavor，0.23 mm vs. 0.58 mm; P<0.001，3组患者临床结果相当（如下图）.

两种因素共抗再狭窄
      “永久聚合物涂层药物支架长时间在冠脉内停留，必然会导致如晚期支架内再狭窄等一系列问题的发生，” Dr. Byrne在他的报告中解释，并且还强调，“无聚合物支架由于其药物不能得到最佳释放，故其有效性因此受到限制。因此，引入另外一种可作用于再狭窄过程的药物，有望成为提高多聚物支架抗再狭窄能力的新选择。” Dr. Byrne进一步强调，这是有关双支架的首次成功报道，他避免了因永久聚合物存在而造成的安全性问题，但是其永久性和有效性尚待进一步试验证实。

      在听完Dr. Byrne’s的报告后，Peter J. Fitzgerald首先对ISAR研究组将不同的药物支架平台方面的工作给予高度评价，并认为，无聚合物支架是在原来基础上加用另一种药物来减少内膜增生。Fitzgerald教授称，目前尚不清楚这种效应是仅见于普罗布考，还是也能见于其他物质。然而，由于ISAR-TEST 2试验的样本量较小且随访时间较短，双重DES的安全性问题现在仍无法回答。

（医心评论: 马秀芹 译  朱婧 校)

ISAR-TEST 2: “Dual DES” Similar to Cypher, Surpasses Endeavor

Polymer-free stents eluting both probucol and sirolimus, dubbed "Dual DES," achieve similar levels of restenosis and in-stent late lumen loss as permanent-polymer sirolimus-eluting Cypher stents, according to results from the ISAR-TEST 2 trial presented at TCT 2008 on Thursday, October 16. In the same study, both Cypher and Dual DES performed better than the Endeavor permanent polymer zotarolimus-eluting stent.

Probucol is a potent lipophilic antioxidant, said study investigator Robert A. Byrne, MD, of Deutsches Herzzentrum (Munich, Germany), which has been shown to reduce restenosis in both animal models and clinical trials.
ISAR-TEST 2 randomized 1,007 patients with de novo coronary lesions to receive Dual DES, Cypher (Cordis/Johnson & Johnson, Miami Lakes, FL), or Endeavor (Medtronic Vascular, Santa Monica, CA) stents.
 In-segment binary angiographic restenosis (primary endpoint) and ischemic target lesion revascularization (TLR) were similar between the Dual DES and Cypher groups. However, the Endeavor showed significantly less favorable results than Dual DES for both of these outcomes (figure 1).
 
 Late lumen loss was also similar for Dual DES vs. Cypher (0.23 mm vs. 0.26 mm; P=0.78) and significantly better with Dual DES vs. Endeavor (0.23 mm vs. 0.58 mm; P<0.001). Clinical outcomes, however, were comparable among all of the treatment groups (figure 2).

 Two Agents to Combat Restenosis
 “Long-term polymer residue in the coronary milieu is a consequence of current drug-eluting stent therapy and has been implicated in late adverse events such as delayed stent thrombosis,” Dr. Byrne explained in his presentation, noting that polymer-free stents can, however, suffer "certain efficacy limitations related to suboptimal release kinetics of the active drug. The incorporation of a second active agent targeted at a different element of the restenotic response cascade is one potential option to enhance the anti-restenotic performance of a polymer-free drug-eluting stent platform."
 
 Dr. Byrne noted that this is the "first report of a successful outcome" with Dual DES. However, while "avoidance of durable polymer has interesting potential long-term safety implications, the durability of performance efficacy and accrual of putative clinical benefit remain subject to future investigation and longer term study," he concluded.
 
 Commenting on Dr. Byrne’s presentation, Peter J. Fitzgerald, MD, PhD, of Stanford University Medical Center (Stanford, CA), praised the ISAR research group for its work in formulating different stent platforms. Evidently, polymer-free stent formulations are made possible by the addition of a biologic to "enhance the overall attenuation of intimal hyperplasia,” explained Dr. Fitzgerald, adding that he is not sure whether the effect is specific to probucol or arises from biologics in general. “Safety issues, however, are not addressed because of [ISAR-TEST 2’s] small sample size and [short duration of] follow-up."