Biolimus A9-eluting Stent Noninferior to Taxus Liberte

　　在NoboriⅡ期临床试验中，血管造影及IVUS证据亦显示出Biolimus A9 药物洗脱支架的优势。

　　最新试验

　　法国du Nord心脏中心Bernard R. Chevalier医生报道的Nobori I 临床试验2期结果显示：9个月时Biolimus A9 药物洗脱支架不逊于Taxus Liberte紫杉醇－药物洗脱支架。次要终点为Nobori 支架的优越性在晚期管腔丢失，再狭窄和新生内膜容积方面也得到证实。

　　Nobori 支架（泰尔茂）与Taxus Liberte支架(波士顿科技) 晚期管腔丢失分别为0.11mm 和 0.32mm（劣势比：P<0.001；优势比P＝0.001）。在全部243例患者中，Nobori支架组与Taxus Liberte支架组相比，心源性死亡率为0.7% vs 1.1%，心梗的发生率为3.3% vs 4.4%；总的主要不良心脏事件（MACE）发生率为3.9% vs 5.6%。但以上结果均无统计学差别。

　　Nobori支架详细情况

　　Nobori支架使用了可降解多聚物涂层以及biolimus A9洗脱层；该药物与其它相关药物相比更具亲脂性，它从支架上洗脱速度更快。1期试验是将Nobori支架与Taxus Express支架进行对比，但在2期转为与Taxus Liberte支架比较。

　　入选该研究患者为1处新发病变或2处新发病变位于不同血管的冠心病患者；靶病变长度小于25mm，参考血管直径为2.5mm-3.5mm。主要的排除标准为对PCI相关药物过敏，左主干病变，分叉病变，靶病变处血栓，靶病变近端或远端有＞50%狭窄的病变，完全闭塞病变（TIMI 血流0或1级），计划在介入治疗后6个月内行择期外科大手术的患者。

　　全部243例患者中，入Nobori支架组153人。除Taxus支架组有较多的糖尿病患者（27.8% vs 16.3%; P=0.048），两组基线水平没有差别。而胰岛素依赖性糖尿病患者更多分布于Nobori组（7.2% VS 2.2%; P＝0.008）。

　　晚期管腔丢失的分布分析显示，病变近端、远端及支架节段内无显著性差异。但Nobori组的支架内晚期丢失明显改善（图）

　　9个月狭窄率亦优于Taxus组（14.0% vs 20.8%；P<0.001）, 再狭窄率亦如此（0.7% vs 5.4%；P＝.049）。Nobori支架组无支架内血栓形成，而Taxus支架组发生2例。

　　概要
　　

　　Chevalier说“Nobori支架在晚期管腔丢失，再狭窄率及内膜容积方面无论血管造影还是IVUS结果显示均优于Taxus liberte支架”“在I期实验中，Nobori支架再次证实其良好的安全性和有效性。”

　　来自华盛顿的Ron Waksman医生对Nobori I期研究给予严格地评价。他说，尽管该试验结果显示Nobori支架有着广阔的前景，“但是本研究在临床事件方面检验效能还不足以得到Nobori支架并不逊于Taxus支架的结论”他附加说道用这种方法进行支架之间比较，晚期管腔丢失可能并不是最佳替代终点。

　　“显而易见，从长远来看，这是一种引人注目的支架，我们需要更多的研究来证实是否Nobori支架确实优于Taxus或Cypher支架。”

　　 (阜外心血管病医院　宋会军　高立建　编译)

Biolimus A9-eluting Stent Noninferior to Taxus Liberte

Angiographic and IVUS evidence also indicated superiority in phase 2 trial.

Nine-month results from the Nobori 1 phase 2 trial showed that the Nobori biolimus A9-eluting stent was noninferior to the Taxus Liberte paclitaxel-eluting stent. The secondary endpoint of superiority of the Nobori stent also was achieved with regard to late loss, restenosis, andneointimal volume.

Late loss for Nobori (Terumo) was 0.11 mm vs. 0.32 mm for Taxus Liberte (Boston Scientific; P<0.001 for noninferiority, P =0 .001 for superiority). Among the 243 total patients, the rate of cardiac death was 0.7% for Nobori and 1.1% for Taxus Liberte, and the rates of MI were 3.3% and 4.4%, respectively; the overall rate of major adverse cardiac events (MACE) was 3.9% for Nobori and 5.6% for Taxus Liberte. These differences were not statistically significant. The results were presented by Bernard R. Chevalier, MD, of the Centre Cardiologie du Nord in Saint-Denis, France.

Nobori details

The Nobori stent uses a biodegradable polymer coating and elutes biolimus A9; the drug is more lipophilic than related drugs, and it elutes very quickly from the stent. The phase 1 version of the trial compared Nobori with Taxus Express, but in phase 2 switched to the Taxus Liberte.

The trial included patients with up to 2 de novo lesions located in 2 epicardial vessels; the target lesion length was <25 mm and reference vessel diameter was 2.5 mm to 3.5 mm. The main exclusion criteria were allergies to PCI-associated drugs, left main CAD, bifurcation, visible thrombus in the target lesion, stenosis >50% proximally or distally to the target lesion, totally occluded lesions (TIMI of 0 or 1), or planned major surgery within 6 months postprocedure.

Of the 243 patients, 153 were in the Nobori group. There were no significant demographic differences at baseline, with the exception of diabetes: there were more diabetic patients in the Taxus group (27.8% vs. 16.3%; P = .048) and more insulin-dependent diabetic patients in the Nobori group (7.2% vs. 2.2%; P = .008).

Analysis of late loss distribution showed nonsignificant differences with regard to proximal, distal, and in-segment late loss. In-stent late loss, however, was significantly improved in the Nobori group (Figure). Nine-month stenosis was better in the Nobori group vs. the Taxus group as well (14.0% vs. 20.8%; P<0.001), as was the rate of binary restenosis (0.7% vs. 5.4%; P = .049). There were no instances of stent thrombosis in the Nobori group and two in the Taxus group.

Summary

“Angiographic and IVUS results [regarding] late loss, restenosis rate, and neointimal volume showed superiority of the Nobori stent vs. the Taxus Liberte,” Chevalier said. “Nobori confirmed its excellent safety and efficacy profile consistent with the phase 1 trial.”

Ron Waksman, MD, of the Washington Hospital Center in Washington, DC, gave a critical appraisal of the Nobori I study. He said that although the results are clearly promising, “the study was underpowered to detect noninferiority to Taxus for clinical events.” He added that late loss may not be the best surrogate endpoint for this type of stent comparison.

“Clearly it is an interesting stent to look at in the future, and we need more studies to confirm whether Nobori will indeed be a better stent than Taxus or Cypher,” Waksman said.