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

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.

Funding: Boston Scientific.