ENDEAVOR III 验证试验证实与以往ENDEAVOR试验一致的临床结果

Endeavor与Cypher间临床结果无统计学差异
尽管以细微之差未达血管造影主要终点

中国，北京 － 11月3日，2005年 －Fugua心脏中心主席、美国乔治亚州亚特兰大Emory医学院内科教授、MACC FESC, Spencer B. King 医生今天在中国北京第16届长城国际心脏学大会上公布了ENDEAVOR III临床试验的结果。ENDEAVOR III，一个验证试验，证实了Endeavor™药物洗脱冠脉支架可提供与以往Endeavor试验一致的临床及血管造影结果。

 “此试验的两个目的是比较Endeavor支架和Cypher支架的节段内晚期丢失，同时也为了解在全球性的ENDEAVOR II试验中Endeavor支架获得的较好的血管造影和临床结果能否在美国病人群中重复，”King博士说，“不次于终点虽未达到，但作为验证试验，此试验确实显示在美国人群中同样能得到安全性和有效性结果。此试验得出的一个主要信息是ENDEAVOR III的临床及血管造影结果与ENDEAVOR II所见相同。另外， Endeavor和Cypher间临床结果无统计学显著差异。但是，就输送性及较低的院内心梗而言，此试验确实显示Endeavor有更显著的手术成功率。”

ENDEAVOR III是由美敦力公司（MDT）主办的一个随机试验，旨在评估与Codis公司（一个强生公司）已上市的Cypher^TM 西罗莫司支架相比，被覆ABT－578药物的Endeavor支架的安全性和有效性。此试验共入选436名病人，按3：1比例随机（323名病人接受Endeavor治疗），其主要终点为8个月时节段内晚期管腔丢失。次要终点包括：9个月时靶病变血运重建（TLR）、靶血管血运重建（TVR）、靶血管失败（TVF）、主要不良心脏事件（MACE）及8个月时造影界定的狭窄（ABR）。方案要求所有病人进行血管造影随访。

数周前在华盛顿特区举办的心血管研究基金会第17届年度经导管心血管治疗学术会议上，美敦力血管部总裁Scott Ward表示，由于已取得各项重要成就，Endeavor临床项目会继续推进。继去年7月获得CE批准后，美敦力已在全球市场成功上市Endeavor支架，并获得医生积极反响。本月初公司向美国食品与药品监督管理局(FDA)提交其第一个PMA的申请，并且另一项大型验证试验ENDEAVOR IV 也如期入选病人。公司预计于2007年获得PMA批准。

 “Endeavor药物洗脱支架的临床表现与我们目前已完成的所有3个主要临床试验非常一致，”Ward说，“全部Endeavor试验的综合分析显示1,300名接受Endeavor支架的病人中95.1％在术后9个月内无需靶病变血运重建。同时我们对Endeavor的安全性保有信心，因为我们观察到在我们的任何试验中Endeavor均无晚期支架内血栓。事实上，在1,300名病人中我们观察到术后10天起即无支架内血栓产生。”

在ENDEAVOR III试验中，Endeavor组节段内晚期丢失为0.34mm，与ENDEAVOR II观察到的一致，而Cypher支架晚期丢失为0.13mm。0.21mm的差异以微弱之势未达不次于终点要求的0.20mm的界限。但值得注意的是，晚期丢失是一个血管造影学的替代指标，临床终点如TLR及MACE才具有代表性地被临床医生认为更为重要。

 “我们通常不会因为考虑到晚期丢失而将病人送回导管室，” King 说，“相反，只有与再狭窄发生有关的症状复发时才那样做。应引起关注的是晚期丢失的差异并非意味了任何临床结果的不同。”

在此试验中，Endeavor组TLR率为6.3%，与以往的ENDEAVOR II中接受血管造影的Endeavor病人的5.8%几乎相同。尽管由于Cypher组病人只有113名，试验不足以证实次要终点的统计学意义，但ENDEAVOR III 中Cypher组的TLR率为3.5%。Endeavor组30天MACE率为7.6% ，非Q波心梗（心脏病发作）率为0.6%，而Cypher组为7.1%，非Q波心梗率达3.5%。另外，Endeavor手术成功率98.1%，较Cypher的91.2%有统计学差异，证明Endeavor有更好的输送性。两组均未发生早期和晚期支架血栓。

 “Endeavor临床项目继续提供有力证据，证实该支架对病人是安全的且能有效降低靶病变血运重建，”纽约哥伦比亚大学医院、心脏研究基金会主席、ENDEAVOR III联合主要研究者Martin B. Leon博士说，“ENDEAVOR IV，具有临床终点而非血管造影替代终点，应能对Endeavor支架系统提供更富洞察力的数据，我们期待着试验的结果。”

ENDEAVOR IV试验是在北美洲80个中心进行的随机试验，在1,548名病人中比较Endeavor支架和波士顿科学的Taxus支架。其主要临床终点是9个月时靶血管失败。该试验预计在2006年上半年完成入选。

Endeavor支架由钴合金制成，其独特的模块结构提供优于一般裸支架的输送性。除了特有的ABT－578药物，Endeavor支架以磷酸胆碱（PC）涂层，此多聚物模拟红细胞表面及正常细胞膜的结构。

关于美敦力
美敦力公司(www.medtronic.com),总部设在美国明尼苏达州明尼阿波利斯市，在医疗技术方面处于全球领先地位――为世界百万人减轻病痛，恢复健康，延长寿命。

此新闻稿含有预见性陈述，包括涉及预期的政策批准和试验完成日期的陈述。这些陈述可能具有风险和不确定性，如政府法规、整体经济状况及其他美敦力年度报告（2005财政年）10－K表格中所述的情况。实际结果可能与预期有较大不符。美敦力不保证更新其预见性陈述。
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注意：Endeavor药物洗脱冠脉支架是具有研究性药物（ABT－578）的研究性器械，只用于临床研究。

English version

ENDEAVOR III CONFIRMATORY STUDY DEMONSTRATES CLINICAL OUTCOMES CONSISTENT WITH PREVIOUS ENDEAVOR TRIALS

No Statistical Differences in Clinical Outcomes Between Endeavor and Cypher
Despite Narrowly Missing Angiographic Primary Endpoint

Beijing, China – November 3, 2005 – Spencer King MD MACC FESC, Fuqua Heart Center/Piedmont Hospital, Atlanta, Georgia, USA, today presented results of the ENDEAVOR III clinical trial at the 16th Great Wall International Congress of Cardiology scientific symposium in Beijing, China.  The ENDEAVOR III trial, a confirmatory study, demonstrated that the Endeavor™ drug-eluting coronary stent provides clinical and angiographic outcomes that are consistent with previous Endeavor trials.

“The two objectives of this trial were to compare in-segment late loss between the Endeavor stent and the Cypher stent, and also to see if the superior angiographic and clinical results achieved with the Endeavor stent in the international ENDEAVOR II trial could be replicated in a United States patient population,” said Dr. King. “The non-inferiority endpoint was not reached, but as a confirmatory study, this trial definitively showed that the safety and efficacy results were achievable in a U.S. population. One of the key takeaways from this trial should be that the ENDEAVOR III clinical and angiographic outcomes are equivalent to those seen in ENDEAVOR II. In addition, there were no statistically significant differences in the clinical outcomes between Endeavor and Cypher. However, the study did show a significant procedure success rate in favor of Endeavor when it came to deliverability and a lower rate of in-hospital myocardial infarctions.”

Sponsored by Medtronic, Inc. (NYSE: MDT), ENDEAVOR III was a randomized trial evaluating the safety and efficacy of the Endeavor stent with the drug compound ABT-578 compared to the Cypher™ Sirolimus-eluting stent marketed by Cordis Corporation, a Johnson & Johnson company.  The study included 436 patients randomized 3-to-1 against Cypher (323 receiving Endeavor), with a primary endpoint of in-segment late lumen loss at eight months.  Secondary endpoints included Target Lesion Revascularization (TLR), Target Vessel Revascularization (TVR), Target Vessel Failure (TVF) and Major Adverse Cardiac Events (MACE) at nine months, and Angiographic Binary Restenosis (ABR) at eight months. The ENDEAVOR III protocol mandated angiographic follow-up for all patients.

At the Cardiovascular Research Foundation’s (CRF) Seventeenth Annual Transcatheter Cardiovascular Therapeutics scientific symposium in Washington, D.C. several weeks earlier, Scott Ward, president of Medtronic Vascular, noted that the Endeavor clinical program is continuing to gain momentum as various key milestones have now been achieved. Following CE mark approval in late July, Medtronic has successfully launched the Endeavor stent in international markets, with positive physician feedback. The company filed its first PMA module with the U.S. Food and Drug Administration earlier this month, and enrollment in ENDEAVOR IV, another large confirmatory trial, is progressing as planned. The company remains on track for PMA approval in calendar year 2007.

“The clinical performance of the Endeavor drug-eluting stent has been remarkably consistent in all three of our major clinical trials completed to date,” said Ward. “The combined analysis across the entire spectrum of Endeavor trials reveals that 95.1% of the 1,300 patients receiving the Endeavor stent did not need target lesion revascularization in the nine months following the procedure. We also continue to be very encouraged by our safety profile, as we have observed no late stent thrombosis with Endeavor in any of our trials. In fact, among these 1,300 patients, we have observed no stent thrombosis beyond 10 days of the procedure.”

In the ENDEAVOR III trial, the Endeavor arm showed an in-segment late loss of 0.34mm, consistent with the rate observed in ENDEAVOR II, while the Cypher stent had late loss of 0.13mm. The 0.21mm difference narrowly missed the margin of ≤0.20mm required to achieve the non-inferiority endpoint. It is important to note, however, that late loss is an angiographic surrogate marker and clinical endpoints such as TLR and MACE are typically considered more important by clinicians.

“We don’t routinely bring patients back to the cath lab because of concerns over late loss,” King said. “Instead, we bring them back due to recurrent symptoms related to the development of restenosis. What is very interesting is that the observed difference in late loss did not translate into differences in any of the clinical results.”

In the trial, the TLR rate for Endeavor was 6.3%, nearly identical to the 5.8% for Endeavor patients who underwent angiography in the previous ENDEAVOR II trial. The TLR rate for Cypher in ENDEAVOR III was 3.5%, although with only 113 patients in the Cypher arm, the study was not “powered” for statistical significance of secondary endpoints. The MACE rate in the Endeavor arm was 7.6% with a non-Q wave myocardial infarction (heart attack) rate at 30 days of 0.6%, while Cypher was 7.1% with a 3.5% myocardial infarction rate. In addition, Endeavor proved to be better than Cypher in deliverability, with a procedural success rate of 98.1% compared to 91.2% for Cypher, a statistically significant finding. Early and late stent thrombosis did not occur in either group.

“The Endeavor clinical program continues to provide strong evidence that this stent is safe for patients and effective at reducing target lesion revascularization,” said Martin B. Leon, M.D., Columbia University Hospital, New York, chairman of the Cardiac Research Foundation and ENDEAVOR III co-principal investigator. “The ENDEAVOR IV study, which has a clinical endpoint instead of an angiographic surrogate, should provide even more insightful information about the Endeavor stent system and we look forward to the results of that trial.”

The ongoing ENDEAVOR IV trial is a randomized study at 80 centers in North America comparing the Endeavor stent with the Taxus stent from Boston Scientific in 1,548 patients. The primary clinical endpoint of the study is target vessel failure at 9 months. The study is on pace to complete enrollment in the first half of 2006.

The Endeavor stent is made of a cobalt alloy and has a unique modular architecture designed to enhance deliverability over standard bare metal stents. In addition to the proprietary drug compound ABT-578, the Endeavor stent is coated with phosphorylcholine (PC), a polymer designed to simulate the outside surface of a red blood cell and mimic the structure of the natural cell membrane.

About Medtronic

Medtronic, Inc. (www.medtronic.com), headquartered in Minneapolis, MN, USA is the global leader in medical technology – alleviating pain, restoring health, and extending life for millions of people around the world. 

This press release contains forward-looking statements, including statements regarding anticipated regulatory approval and study completion dates, which are subject to risks and uncertainties, such as governmental regulation, general economic conditions and others described in Medtronic’s Annual Report on Form 10-K for the year ended April 29, 2005. Actual results may differ materially from anticipated results. Medtronic does not undertake to update its forward-looking statements.

Caution: The Endeavor Drug Eluting Coronary Stent is an investigational device with an investigational drug (ABT-578) and exclusively for clinical investigation.