（表1）治疗组的基线临床和超声心动图特征平衡良好，组间唯一的差异是高血压和既往卒中。平均年龄为83岁，395名患者为女性。STS-PROM平均评分为6.5%，521名患者的平均虚弱指数为2或更高，541名患者为NYHA III级或IV级，133名患者被认为有极高的手术风险。
（表2）事后优势测试表明，在治疗人群中，市售瓣膜在主要安全终点方面优于Portico瓣膜。1年时，治疗组和符合方案的人群均在主要疗效终点的非劣效性范围内。
（图3C）对于瓣膜性能的事后分析，Portico瓣膜与Evolut R和Evolut PRO瓣膜的平均主动脉瓣压差和主动脉瓣面积相似，随访时间长达2年。
（图3D）与SAPIEN 3瓣膜相比，主动脉瓣压梯度较低，主动脉瓣面积较高。
在手术后30天、1年和2年，Portico瓣膜接受者比SAPIEN 3瓣膜接受者更频繁地发生中度或更严重的瓣周漏，但Portico瓣膜受体和Evolut R或Evolut Provalves受体之间没有差异。在ITT人群中，Portico瓣膜组在30天内出现中度或重度瓣周漏的患者在2年内的死亡率高于那些没有或只有微量瓣周漏患者，尽管这种差异没有达到显著性。术后30天，Portico瓣膜接受者的新永久性起搏器植入率高于Evolut R或Evolut PRO瓣膜以及SAPIEN 3瓣膜接受者。
在接受经导管主动脉瓣置换术的严重主动脉瓣狭窄的高危和极端风险患者中，从这项临床试验中得出了五个主要发现。
首先，与美国食品药品监督管理局批准的球囊扩张或环上自扩张瓣膜相比，环内自扩张Portico瓣膜在ITT分析中符合预先规定的非劣效性安全界限，但Portico瓣膜组在30天内观察到更高的死亡率和血管并发症率，这可能与研究前半部分的新器械学习有关。
其次，与商用瓣膜相比，Portico瓣膜在1年内死亡或致残卒中的复合疗效终点的发生率相似。
第三，使用Portico瓣膜可以减少心脏症状，改善生活质量，与商业瓣膜相似。
第四，随访2年的瓣膜功能评估显示，Portico瓣膜的瓣膜面积比商用瓣膜大，平均压差低。
第五，事后12项分析显示，Portico瓣膜和单个当代商用瓣膜在临床结果和瓣膜性能方面存在差异。
Background:Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs.
Methods:In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing.
Findings:Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI -0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI -3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups.
