美国雪松西奈医疗中心Raj R Makkar团队近日比较了ACURATE neo2瓣膜与市售经导管心脏瓣膜治疗严重主动脉瓣狭窄患者的效果。这一研究成果于2025年5月21日发表在《柳叶刀》杂志上。

ACURATE neo2是一种开细胞、环上、自我扩张的经导管心脏瓣膜，已在50多个国家上市，但此前尚未在随机试验中进行评估。ACURATE-IDE旨在前瞻性评估经导管主动脉瓣置换术（TAVR）与市售瓣膜治疗严重症状性主动脉瓣狭窄的安全性和有效性。

在这项多中心、随机、对照、非劣效性试验中，研究组从美国和加拿大的71个医疗中心招募了有症状的严重主动脉瓣狭窄和任何手术风险的患者。符合条件的患者被随机（1:1）分配到使用ACURATE neo2或控制阀之一的TAVR， SAPIEN 3 （SAPIEN 3或SAPIEN 3 Ultra）或Evolut，使用伪随机数生成器进行排列块随机化，并根据临床研究地点和控制阀类型进行分层。所有装置都是按照制造商的说明植入的。主要终点是全因死亡率、全卒中和1年后再住院的综合数据，使用贝叶斯方法进行非劣效性检验。初步分析在意向治疗人群中进行，敏感性分析在植入人群中进行。非劣效性边际为8.0%。

在2019年6月10日至2023年4月19日期间，共招募了1500名患者，其中752名被随机分配到ACURATE neo2组，748名被分配到对照组。参与者的中位年龄为79岁（IQR 74-83）。1500例患者中，女性778例（51.9%），男性721例（48.1%）。在1年时，ACURATE neo2组主要复合终点的后验中位数概率（16.2%[95%贝叶斯可信区间13.4 - 19.1]）高于对照组(9.5% [7.5 - 11.9]；组间差异6.6%[3.0 ~ 10.2])。治疗差异的上界超过了预定的8%的非劣效性边界，治疗差异的后验概率为>； 0.999。

1年时，ACURATE neo2组的全因死亡率、全卒中和再住院的Kaplan-Meier复合终点率显著更高(14.8% vs 9.1% [7.2 - 11.4]；风险比[HR] 1·71；p = 0·0005)。1年后，ACURATE neo2组752例患者中有36例发生全因死亡，对照组748例患者中有28例发生全因死亡（HR为1.30），41例患者发生卒中，25例患者发生卒中（HR为1.68[1.02 - 2·75]），38例患者再次住院，25例患者再次住院（HR为1.57[0.95 - 2·61]）。心血管死亡率（3.7% vs 1.8%, p= 0.024）和1年后自发性心肌梗死（2.4% vs 0.7%, p= 0.0092）在ACURATE neo2组比对照组更常见。ACURATE neo2组1年主动脉瓣反流（中央和瓣旁）发生率明显高于对照组(轻度主动脉瓣反流42.5% vs 24.8%, p< 0.0001；中度4·4% vs 1·8%，p= 0.0070；严重0.5% vs 0%；p = 0·12)。

研究结果表明，在有症状的严重主动脉瓣狭窄患者中，与商用瓣膜相比，使用ACURATE neo2的TAVR不符合非劣效性，并且与全因死亡率、全卒中和1年后再住院的综合主要终点相比，预后明显更差。

附：英文原文

Title: ACURATE neo2 valve versus commercially available transcatheter heart valves in patients with severe aortic stenosis (ACURATE IDE): a multicentre, randomised, controlled, non-inferiority trial

Author: Raj R Makkar, Ravi K Ramana, Eric Gnall, Basel Ramlawi, Wen Cheng, Pantelis Diamantouros, Srinivasa Potluri, Neal Kleinman, Aakriti Gupta, Tarun Chakravarty, Sanjay Samy, Andrew Rassi, Vivek Rajagopal, Steven Yakubov, Paul Sorajja, Dhairya Patel, Santiago Garcia, Pradeep Yadav, Vinod Thourani, John Wang, Michael Rinaldi, Samir Kapadia, Ron Waksman, John Webb, Claire Ben Ren, John Gregson, Rodrigo Modolo, Janarthanan Sathananthan, Michael J Reardon

Issue&Volume: 2025-05-21

Abstract:

Background

ACURATE neo2 is an open-cell, supra-annular, self-expanding transcatheter heart valve that is commercially available in over 50 countries but has not previously been evaluated in a randomised trial. ACURATE-IDE aimed to prospectively evaluate the safety and efficacy of transcatheter aortic valve replacement (TAVR) with the ACURATE neo2 valve compared with commercially available valves for the treatment of severe symptomatic aortic stenosis.

Methods

In this multicentre, randomised, controlled, non-inferiority trial, patients with symptomatic severe aortic stenosis and any level of surgical risk were recruited from 71 medical centres in the USA and Canada. Eligible patients were randomly assigned (1:1) to TAVR with ACURATE neo2 or one of the control valves, SAPIEN 3 (SAPIEN 3 or SAPIEN 3 Ultra) or Evolut, using permuted block randomisation with a pseudo-random number generator, and stratified by the clinical investigation site and type of control valve. All devices were implanted according to the manufacturer's instructions. The primary endpoint was a composite of all-cause mortality, all stroke, and rehospitalisation at 1 year, tested for non-inferiority using a Bayesian approach. The primary analysis was performed in the intention-to-treat population and sensitivity analyses were done in the implanted population. The non-inferiority margin was 8·0%. This study is registered with ClinicalTrials.gov, NCT03735667, and is ongoing.

Findings

Between June 10, 2019, and April 19, 2023, 1500 patients were recruited, of whom 752 were randomly assigned to the ACURATE neo2 group and 748 to the control group. The median age of participants was 79 years (IQR 74–83). 778 (51·9%) of 1500 patients were female and 721 (48·1%) were male. At 1 year, the posterior median probability of the primary composite endpoint was higher in the ACURATE neo2 group (16·2% [95% Bayesian credible interval 13·4–19·1) than in the control group (9·5% [7·5–11·9]; between-group difference 6·6% [3·0–10·2]). The upper bound of treatment difference exceeded the prespecified non-inferiority margin of 8%, with a posterior probability of treatment difference of >0·999. At 1 year, the ACURATE neo2 group, had significantly higher Kaplan–Meier rates of the composite endpoint of all-cause mortality, all stroke, and rehospitalisation (14·8% [95% CI 12·5–17·6] vs 9·1% [7·2–11·4]; hazard ratio [HR] 1·71 [95% CI 1·26–2·33]; p=0·0005). At 1 year, all-cause mortality occurred in 36 of 752 patients in the ACURATE neo2 group versus 28 of 748 patients in the control group (HR 1·30 [95% CI 0·80–2·14]), stroke in 41 patients versus 25 patients (1·68 [1·02–2·75]), and rehospitalisation in 38 patients versus 25 patients (1·57 [0·95–2·61]). Cardiovascular mortality (3·7% vs 1·8%, p=0·024) and spontaneous myocardial infarction at 1 year (2·4% vs 0·7%, p=0·0092) were more frequent in the ACURATE neo2 group than in the control group. Prosthetic valve aortic regurgitation (central plus paravalvular) at 1 year was significantly more frequent in the ACURATE neo2 group than in the control group (mild aortic regurgitation 42·5% vs 24·8%, p<0·0001; moderate 4·4% vs 1·8%, p=0·0070; severe 0·5% vs 0%; p=0·12).

Interpretation

In patients with symptomatic severe aortic stenosis, TAVR with ACURATE neo2 did not meet non-inferiority and resulted in significantly worse outcomes with respect to the primary endpoint of composite of all-cause mortality, all stroke, and rehospitalisation at 1 year when compared with commercial valves.

DOI: 10.1016/S0140-6736(25)00319-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00319-8/abstract