Transcatheter aortic valve implantation with the Trilogy valve for symptomatic native aortic regurgitation (ALIGN-AR): A pivotal, multicentre, single-arm, investigational device exemption study
Recommended Citation
Makkar RR, Thourani VH, Vahl TP, et al. Transcatheter aortic valve implantation with the Trilogy valve for symptomatic native aortic regurgitation (ALIGN-AR): a pivotal, multicentre, single-arm, investigational device exemption study. Lancet. Published online November 16, 2025. doi:10.1016/S0140-6736(25)02215-9
Abstract
Background: Transcatheter devices designed for calcific aortic stenosis are not optimised for use in native aortic regurgitation, and data on aortic regurgitation-dedicated platforms are limited. The extended ALIGN-AR pivotal experience with a prospectively enrolled continued-access cohort and longer follow-up aimed to characterise the safety, valve function, and clinical outcomes of transcatheter aortic valve intervention (TAVI) with a dedicated device in aortic regurgitation.
Methods: ALIGN-AR is a prospective, multicentre, single-arm study enrolling patients at high surgical risk to undergo TAVI with a dedicated valve (Trilogy valve) for symptomatic moderate-to-severe or severe aortic regurgitation at 30 centres in the USA. Coprimary endpoints were a safety composite of major adverse events within 30 days post procedure (all-cause death, stroke, life-threatening or major bleeding, acute kidney injury, major vascular complications, need for additional surgical or percutaneous interventions, new pacemaker implantation, and moderate or greater aortic regurgitation), tested for non-inferiority against a margin of 1·35 applied to literature-based incidence of safety endpoint of 30% translating to performance goal of 40·5%, and 1-year all-cause mortality, tested for superiority against a performance goal of 25·0%. Analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04415047), and is ongoing.
Findings: Between June 8, 2018, and July 29, 2025, we screened 1352 patients and enrolled 700 patients (pivotal cohort n=180; continued access cohort n=520). Median age was 79·0 years (IQR 72·0-84·0), 321 (46%) were female, 379 (54%) were male, and 532 (76%) were White, 68 (10%) were Black or African American, and 36 (5%) were Asian. Technical success was achieved in 664 (95%) patients. The median duration of follow-up was 472 days (IQR 352-891). The 30-day primary safety composite endpoint occurred in 168 patients (24·0% [upper 97·5% CI 27·3%]; pnon-inferiority<0·0001), meeting the performance goal. Among components of the composite safety endpoint, death occurred in 11 (1·6%), stroke in 12 (1·7%), new pacemaker implantation in 127 (21·6%) of 589, moderate aortic regurgitation in three (0·5%) of 569 and severe aortic regurgitation in none. All-cause mortality occurred in 38 at 1 year (7·7% [upper 97·5% CI 10·4%]; psuperiority<0·0001), meeting the performance goal, and in 53 (13·3%) at 2 years.
Interpretation: In patients with symptomatic moderate-to-severe or severe aortic regurgitation considered to be of high surgical risk, TAVI with a dedicated platform met prespecified safety and effectiveness performance goals. We observed substantial reductions in aortic regurgitation, favourable valve haemodynamics and myocardial remodelling, with associated improvements in functional status and quality-of-life gains up to 2 years. These data support TAVI with a purpose-built device as a feasible and effective treatment option for selected patients with native aortic regurgitation who are at high risk for death or complications after surgery.
Document Type
Article
PubMed ID
41260228
Affiliations
Advocate Christ Medical Center