Next-generation DES Targeting More Complex Lesions

　　在安全性和有效性上，到目前为止第一代和第二代药物洗脱支架的临床结果是相似的。下一代以治疗特殊复杂病变为目的的DES还需经过长期的临床检验，来自德国的Grube医生说。

　　Grube医生回顾了期待2008年在美国上市的第二代药物洗脱支架Endeavor (美敦力) 和 Xience V (雅培)支架的临床试验结果，并展望了现在欧洲正在和研制的其他新型药物洗脱支架的前景。他讲道第一代支架Cypher 和Taxus已经经过了比较彻底的研究，到目前为止第二代支架还缺乏一些重要的临床数据资料。经过了早期的安全性和有效性研究后，还需要大规模临床试验比较不同支架的长期安全性。

　　第一代药物洗脱支架已有5年的比较完整的临床随访资料（包括Taxus支架3500人和Cypher支架1800人）。第二代药物洗脱支架Endeavor支架目前也有大约1700例完成2年的比较完整的临床随访。Xience V everolimus洗脱支架有大约1300例完成1年临床随访。为了证实这些新的支架效果等同于或优于第一代药物洗脱支架，长期的研究是增加检验效能所必须的。

　　晚期管腔丢失

　　Grube医生回顾了到目前为止的关于第一代和第二代药物洗脱支架有效性和安全性的临床试验资料。他说药物洗脱支架防止内膜增生，反映内膜增生程度最好的指标是晚期管腔丢失，但在很多试验中所用的是替代指标靶病变重建（TLR）。Grube医生强调在评价临床试验时我们要有这些概念。“在SIRIUS （Cypher支架）和TAXUS IV （TAXUS支架）试验中，3年TLR是相似的，但如用晚期管腔丢失评价，Cypher支架显然具有更好的效果。在比较Endeavor支架和Taxus支架的ENDEAVOR IV试验中,主要有效终点为9个月靶血管重建，第二代DES与第一代支架Taxus没有差别。一篇将要发表在本月JACC杂志上的文章中，作者Kereiakes回顾了29个比较Taxus 和Cypher的临床试验，二者间TLR率方面没有差别。

　　关于安全性的问题，Grube医生回顾了2006 ESC Edoardo Camenzind医生荟萃分析显示：置入Cypher支架组较Taxus支架组Q波心梗有所增加。Grube最后总结时说道“现在我们都知道，事实证明不是这样的”。

　　报告中Grube也提到了关于支架内血栓的定义，定义的不同导致很难在两个试验结果间进行比较。

　　最后Grube呼吁介入医生：如果你们关心药物洗脱支架的长期效果，那么让我们“回到从前的时代“－－使用DES需更加谨慎。他强调“操作技术很重要”。

　　展望

　　展望未来，Grube回顾了新一代支架技术不断在发展，包括可降解生物支架，载体控制支架和无载体支架。

　　最后，Grube也介绍了针对特殊病变如闭塞和分叉病变的特殊支架。Devax支架用于分叉病变，Xtent 系统可提供一个确定长度的支架。

　　（阜外心血管病医院 陈俊 高立建　编译）

Next-generation DES Targeting More Complex Lesions

Clinical efficacy and safety of second-generation DES appear equivalent in trials to date.

The efficacy and safety of second-generation DES appear to be similar to first-generation devices in clinical trial results to date. Next-generation stents, such as lesion-specific DES, hold promise for addressing more complex lesions, but they must first undergo more longterm examination, said Eberhard Grube, MD.

Grube, of HELIOS Klinikum Siegburg, Germany, reviewed clinical trial results for the second-generation DES models Endeavor (Medtronic) and Xience V (Abbott), which are expected to reach the U.S. market in 2008, and looked ahead to the promise of other stent models now available in Europe or in development. He said the first generation of DES- Cypher (Cordis, Johnson & Johnson) and Taxus (Boston Scientific) - are themost thoroughly studied, and the second-generation models that have been introduced are “mostly without a profound database” of experience. After early safety and efficacy studies, longterm safety trials in large patient populations are needed to assess performance differences among devices, he said.

The first-generation stents now have clinical experience extending up to 5 years with near-complete followup in trials that include approximately 3,500 and 1,800 patients for Taxus and Cypher, respectively. Clinical trial experience with the second-generation Endeavor zotarolimus-eluting stent is up to 2 years with near-complete follow-up in approximately 1,700 patients, and clinical experience with the Xience V everolimus-eluting stent is up to 1 year with near-complete follow-up in approximately 1,300 patients.

Adequately powered, long-term studies will be needed to confirm the equivalence or superiority of these newer devices, he said.

Late lumen loss

Grube reviewed some of the safety and efficacy findings in first- and second generation DES in clinical trials to date.

DES efficacy requires the prevention of intimal hyperplasia, he said. The best angiographic surrogate for hyperplasia is late lumen loss, but the surrogate that matters most to the patient is TLR.

The clinician should keep this in mind when evaluating clinical trial results, Grube said. In the pivotal SIRIUS and TAXUS IV trials of Cypher and Taxus, respectively, TLR rates at 3 years were similar, despite significant differences in late lumen loss favoring Cypher.

In the ENDEAVOR IV trial, which compared Endeavor with Taxus, the second-generation device demonstrated noninferiority in the primary efficacy endpoint of target vessel failure at 9 months, Grube said. (See related article on ENDEAVOR IV 1-year results, which were announced at TCT 2007.)

In a broad review of 29 clinical trials comparing Taxus and Cypher, there was no difference in target lesion revascularization between the two devices, Grube said (Figure).

The study, by Kereiakes, is to be published this month in the Journal of the American College of Cardiology.

Regarding safety, Grube recalled the alarm raised at the European Society of Cardiology meeting in 2006, when a meta-analysis by Edoardo Camenzind suggested an increase in Q wave MI with Cypher vs. Taxus.
“That, as we all know, has proven not to be the case,” Grube said.

He noted also that different definitions of stent thrombosis can make it difficult to compare results between trials.
Grube urged operators, if they are concerned about long-term results with DES, to “go back to the early days,” and employ the stents carefully.“Technique does matter,” he said.

The future

Grube also reviewed some of the stent technologies still in development, such as bioabsorbable polymers, controlled application of polymers, and nonpolymer-based devices.

In addition, he said, lesion-dedicated DES are in development to address the needs of complex types of occlusions. These include the Devax stent, for use in bifurcations, and the Xtent system offering customized length with interdigitized stent segments.