Ludwig Sebastian, Klimek Matthias, Bay Benjamin, Blankenberg Stefan, Granada Juan F, Hildick-Smith David, Hudson Jemma, Jørgensen Troels Højsgaard, Leon Martin B, Magnussen Christina, Thiele Holger, Hørsted Thyregod Hans Gustav, Wendler Olaf, de Backer Ole, Toff William D, Ziegler Andreas, Seiffert Moritz
Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Centre for Population Health Innovation, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
JAMA Cardiol. 2025 Aug 30. doi: 10.1001/jamacardio.2025.3403.
Mounting evidence suggests transcatheter aortic valve implantation (TAVI) as preferred treatment for patients at low to intermediate surgical risk. However, limitations in study design and statistical power raise concerns about the generalizability of individual randomized clinical trials (RCTs) comparing TAVI and surgical aortic valve replacement (SAVR) to routine clinical practice.
To compare 1-year outcomes of TAVI vs SAVR in patients with severe symptomatic aortic stenosis at low to intermediate surgical risk applying a 2-stage individual participant data (IPD) and aggregate meta-analyses.
MEDLINE databases were searched for RCTs comparing TAVI and SAVR in patients with aortic stenosis until June 15, 2025.
RCTs were selected comparing TAVI vs SAVR in patients with severe symptomatic aortic stenosis at low or intermediate surgical risk with 1-year follow-up.
IPD were obtained from all investigator-initiated RCTs (DEDICATE, NOTION, NOTION-2, and UK TAVI) and analyzed in 1- and 2-stage IPD meta-analyses. An overall meta-analysis was performed by adding aggregate data from industry-sponsored RCTs.
The primary end point was all-cause death or any stroke 1 year after randomization. Secondary end points included all-cause death, any stroke, disabling stroke, cardiovascular death, rehospitalization for cardiovascular cause, myocardial infarction, new-onset atrial fibrillation, new permanent pacemaker implantation, and aortic valve reintervention.
The IPD meta-analysis included 4 RCTs comprising 2873 patients (mean [SD] age, 76.7 [5.5] years; 805 [56.1%] male) at low to intermediate surgical risk randomly assigned to TAVI (n = 1439) or SAVR (n = 1434). At 1 year, the hazard ratio (HR) for the primary end point for TAVI compared to SAVR was 0.73 (95% CI, 0.56-0.95) in the 1-stage and 0.79 (95% CI, 0.49-1.27) in the 2-stage IPD meta-analysis. In the 2-stage overall meta-analysis the HR for the primary end point was 0.76 (95% CI, 0.60-0.97).
In this IPD meta-analysis of 4 RCTs, and an overall meta-analysis of 8 RCTs of patients with severe symptomatic AS at low to intermediate risk, TAVI was associated with a reduction in the 1-year incidence of all-cause death or any stroke. These findings emphasize TAVI as alternative option in patients at low to intermediate risk. Long-term follow-up is warranted to evaluate sustainability of these findings.
越来越多的证据表明，经导管主动脉瓣植入术（TAVI）是低至中度手术风险患者的首选治疗方法。然而，研究设计和统计效力的局限性引发了人们对比较TAVI与外科主动脉瓣置换术（SAVR）的个体随机临床试验（RCT）能否推广到常规临床实践的担忧。
采用两阶段个体参与者数据（IPD）和汇总荟萃分析，比较TAVI与SAVR在低至中度手术风险的重度症状性主动脉瓣狭窄患者中的1年结局。
检索MEDLINE数据库，查找截至2025年6月15日比较TAVI与SAVR治疗主动脉瓣狭窄患者的RCT。
选择比较TAVI与SAVR治疗低或中度手术风险的重度症状性主动脉瓣狭窄患者且随访1年的RCT。
从所有研究者发起的RCT（DEDICATE、NOTION、NOTION-2和英国TAVI）中获取IPD，并在单阶段和两阶段IPD荟萃分析中进行分析。通过添加行业赞助的RCT的汇总数据进行总体荟萃分析。
主要终点是随机分组后1年的全因死亡或任何卒中。次要终点包括全因死亡、任何卒中、致残性卒中、心血管死亡、因心血管原因再次住院、心肌梗死、新发心房颤动、新植入永久性起搏器以及主动脉瓣再次干预。
IPD荟萃分析纳入了4项RCT，共2873例患者（平均[标准差]年龄，76.7[5.5]岁；805例[56.1%]为男性），这些患者处于低至中度手术风险，随机分配接受TAVI（n = 1439）或SAVR（n = 1434）。1年时，在单阶段IPD荟萃分析中，TAVI与SAVR相比主要终点的风险比（HR）为0.73（95%CI，0.56 - 0.95），在两阶段IPD荟萃分析中为0.79（95%CI，0.49 - 1.27）。在两阶段总体荟萃分析中，主要终点的HR为0.76（95%CI，0.60 - 0.97）。
在这项对4项RCT的IPD荟萃分析以及对8项低至中度风险的重度症状性主动脉瓣狭窄患者的RCT的总体荟萃分析中，TAVI与全因死亡或任何卒中的1年发生率降低相关。这些发现强调TAVI是低至中度风险患者的替代选择。有必要进行长期随访以评估这些发现的可持续性。
