美国旧金山丨2019年9月27日

 

　　第一次随机试验比较在有症状的重度主动脉瓣狭窄患者中应用ACURATE neo经导管心脏瓣膜与SAPIIN 3 TAVR装置的安全性和有效性的非劣性无法成立。

 

 

　　研究结果在第三十一届经导管心血管治疗（TCT）学术会议上公布。该会议由心血管研究基金会（CRF）赞助，是世界上最重要的心血管介入医学教育会议。研究同时发表在《柳叶刀》上。

 

　　在2017年2月~2019年2月期间，在欧洲20个中心，共有739名有症状的重度主动脉瓣狭窄患者1：1随机采用ACURATE neo（n=372）或SAPIEN 3（n=367）系统经股动脉TAVR。30天的临床随访信息占总研究人群的98.9％，超声心动图随访占98.0％。

 

　　这项研究旨在研究主要终点的非劣效性，主要终点为基于VARC-2的30天早期安全性和临床有效性，包括全因死亡率、卒中、危及生命或致残性出血出血、主要血管并发症、需介入开通的冠状动脉闭塞、2期或更严重的急性肾脏损伤、因瓣膜相关功能不全需再次手术、因瓣膜相关症状或慢性心力衰竭（CHF）加重再住院、及中度或重度人工瓣膜返流或人工瓣膜狭窄。

 

　　主要终点发生率上，ACURATE neo组为23.7%，而SAPIEN 3组为16.5%（P非劣效性=0.42，非劣效性无法成立）。两种TAVR设备之间的差异主要在中度或重度瓣周漏以及2或3期急性肾损伤，而SAPIEN 3装置在这方面具有优效性。

 

　　伯尔尼大学附属医院心内科医学博士Jonas Lanz说：“与SAPIEN 3设备相比，ACURATE neo在30天的主要复合安全性和有效性终点并不存在劣效性。事实证明，早期复合安全性和有效性终点可用于区别不同TAVR系统的有效性。”

 

 

　　Transcatheter aortic valve replacement (TAVR) is the preferred treatment option for older patients with symptomatic severe aortic stenosis. Differences in the properties of available TAVR systems can affect clinical outcomes. Among patients undergoing TAVR， we compared the self-expanding ACURATE neo TAVR system with the balloon-expandable SAPIEN 3 TAVR system with regard to early safety and efficacy.

 

　　TAVR是老年有症状的重度主动脉狭窄患者的首选治疗方案。可用的TAVR系统的性能差异影响临床结果。在接受TAVR的患者中，研究者比较自膨式ACURATE neo TAVR系统和球囊扩张SAPIEN 3 TAVR系统的早期安全性和有效性。

 

　　Methods

　　In this randomised non-inferiority trial， patients (aged ≥75 years) undergoing transfemoral TAVR for treatment of symptomatic severe aortic stenosis， and who were deemed to be at increased surgical risk， were recruited at 20 tertiary heart valve centres in Germany， the Netherlands， Switzerland， and the UK. Participants were randomly assigned (1:1) to receive treatment with the ACURATE neo or the SAPIEN 3 with a computer-based randomly permuted block scheme， stratified by study centre and Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) category. The primary composite safety and efficacy endpoint comprised all-cause death， any stroke， lifethreatening or disabling bleeding， major vascular complications， coronary artery obstruction requiring intervention， acute kidney injury (stage 2 or 3)， rehospitalisation for valve-related symptoms or congestive heart failure， valverelated dysfunction requiring repeat procedure， moderate or severe prosthetic valve regurgitation， or prosthetic valve stenosis within 30 days of the procedure. Endpoint assessors were masked to treatment allocation. Non-inferiority of ACURATE neo compared with SAPIEN 3 was assessed in the intention-to-treat population on the basis of a risk difference margin of 7·7% for the primary composite endpoint， with a one-sided α of 0·05. This trial is registered with ClinicalTrials.gov (number NCT03011346) and is ongoing but not recruiting.

 

　　这项随机非劣效性试验，在德国、荷兰、瑞士和英国的20个三级心脏瓣膜中心招募接受经股动脉TAVR治疗的有症状重度主动脉狭窄的高手术风险患者（年龄≥75岁）。受试者被随机分配（1:1）接受ACURATE neo或SAPIEN 3治疗，采用基于计算机的随机分组方案，按研究中心和胸外科医师协会预测死亡率（STS-PROM）类别分层。主要综合安全性和有效性终点包括术后30天内的全因死亡、任何卒中、危及生命或致残性出血、主要血管并发症、需要干预的冠状动脉阻塞、急性肾损伤（2或3期）、因瓣膜相关症状或充血性心力衰竭而重新住院治疗、需再次手术的瓣膜相关功能障碍、中度或重度人工瓣膜返流或狭窄。与SAPIEN 3相比，ACURATE neo的非劣效性在意向治疗人群中的评估基于主要复合终点的7.7%的风险差，单侧α为0.05。这项试验在ClinicalTrials.gov上注册（编号：NCT03011346），目前正在进行中。

 

　　Findings

　　Between Feb 8， 2017， and Feb 2， 2019， up to 5132 patients were screened and 739 (mean age 82?8 years [SD 4·1]; median STS-PROM score 3?5% [IQR 2·6–5·0]) were enrolled. 30-day follow-up was available for 367 (99%) of 372 patients allocated to the ACURATE neo group， and 364 (99%) of 367 allocated to the SAPIEN 3 group. Within 30 days， the primary endpoint occurred in 87 (24%) patients in the ACURATE neo and in 60 (16%) in the SAPIEN 3 group; thus， non-inferiority of the ACURATE neo was not met (absolute risk difference 7?1% [upper 95% confidence limit 12·0%]， P=0?42). Secondary analysis of the primary endpoint suggested superiority of the SAPIEN 3 device over the ACURATE neo device (95% CI for risk difference –1·3 to –12·9， P=0·0156). The ACURATE neo and SAPIEN 3 groups did not differ in incidence of all-cause death (nine patients [2%] vs three [1%]) and stroke (seven [2%] vs 11 [3%]); whereas acute kidney injury (11 [3%] vs three [1%]) and moderate or severe prosthetic aortic regurgitation (34 [9%] vs ten [3%]) were more common in the ACURATE neo group.

 

　　在2017年2月8日~2019年2月2日期间，共筛查5132名患者，纳入739名（平均年龄82 8岁[SD 4.1]；STS-PROM中位得分3 5%[IQR 2.6~5.0]）。372例患者中367例（99%）被分配到ACURATE neo治疗组，367例（99%）被分配到SAPIEN 3治疗组。在30天内，主要终点出现在87名（24%）ACURATE neo组患者和60名（16%）SAPIEN 3组患者中；因此，不满足ACURATE neo的非劣效性（绝对风险差异7.1% [ 95% CI上限12.0%]，P=0.42）。对主要终点的二次分析表明，SAPIEN 3装置优于ACURATE neo装置（风险差异95%CI：–1.3~–12.9，P=0.0156）。ACURATE Neo和Sapien 3组在全因死亡（9 [2%] vs. 3 [1%]）和卒中（7[2%] vs. 11 [3%]）的发生率无差异；而在ACURATE neo组中，急性肾损伤（11[3%] vs. 3[1%]）和中度或重度人工主动脉瓣关闭不全（34[9%] vs. 10[3%]）更为常见。

 

Slides

TCT 2019｜SCOPE I

 

 

 

 

 

　　About CRF and TCT

 

　　The Cardiovascular Research Foundation (CRF) is one of the world’s leading nonprofit organizations specializing in interventional cardiology innovation， research， and education. CRF is dedicated to helping doctors improve survival and quality of life for people suffering from heart and vascular disease. For nearly 30 years， CRF has helped pioneer medical advances and educated doctors on the latest treatments for heart disease. CRF is comprised of the CRF Skirball Center for Innovation， CRF Clinical Trials Center， CRF Center for Education， CRF Digital， TCTMD， and Structural Heart: The Journal of the Heart Team.

 

　　Transcatheter Cardiovascular Therapeutics (TCT) is the annual scientific symposium of CRF and the premier educational meeting specializing in interventional cardiovascular medicine. Now in its 31st year， TCT features major medical research breakthroughs and gathers leading researchers and clinicians from around the world to present and discuss the latest evidence-based research in the field. TCT also includes interactive training pavilions where clinicians can gain vital skills to apply immediately to their practices.

 

　　For more information，

　　visit www.crf.org and www.tctconference.com.