WHY THIS STUDY?

TAVI is an established procedure to treat aortic stenosis irrespective of surgical risk. Several new-generation TAVI devices have been designed by specifically incorporating features to mitigate paravalvular leak, vascular injuries, and conduction disturbances, to improve clinical outcomes. The LANDMARK trial is one of its kind and the first randomized trial in which the long-term (10 years) head-to-head outcomes are being studied to prove the non-inferiority of newer generation balloon-expandable Myval transcatheter heart valve series with commercially available contemporary TAVI devices (Sapien and Evolut transcatheter heart valve series). The primary objective of this study was to compare the safety and effectiveness of Myval with contemporary TAVI devices.

HOW WAS IT EXECUTED?

This is a prospective, multinational, multicentre, open-label, randomized, non-inferiority trial. 768 patients undergoing TAVI for severe native aortic valve stenosis were randomized in a 1:1 ratio [Myval: 384; contemporary ? Sapien: 192, Evolut: 192] from 31 sites across 16 countries between 21 January 2021 and 7 December 2023. The primary endpoint of the study is the combined safety and effectiveness endpoint at 30-day follow-up as per VARC-3 criteria and it is a composite of all-cause mortality, all stroke, bleeding (type 3 and 4), acute kidney injury (stage 2, 3 and 4), major vascular complications, moderate or severe prosthetic valve regurgitation and conduction system disturbances resulting in a new permanent pacemaker implantation. Non-inferiority analyses will be performed on the intention-to-treat population for this primary combined safety and effectiveness endpoint. This study is planned to follow up with the patients at 30-day, 6 months, 1, 2, 3, 4, 5, 7, and 10 years. All the clinical events are being adjudicated by independent clinical events committee. All 30-day echocardiograms and electrocardiograms are being analysed centrally by the CORRIB core lab (Galway, Ireland) and the Cardiovascular European Research Center, France, respectively.

WHAT WERE THE ESSENTIAL RESULTS?

The mean age of the patients in Myval and contemporary transcatheter heart valve series groups was 80.0±5.8 years and 80.4±5.5 years, respectively. The majority of the patients had low Society of Thoracic Surgeons scores (Myval: 76.0%; contemporary: 76.0%) followed by intermediate (20.1%; 19.7%) and high risk (4.0%; 4.3%) scores at baseline. The 30-day follow-up will be completed by January 2024, and the final 30-day results will be presented during the EuroPCR 2024 as a late-breaking trial.

WHY IT IS IMPORTANT?

The unique design of the Myval aids in precise placement, accurate deployment, and size optimization (due to the availability of intermediate and extra-large sizes). All Myval sizes are compatible with low profile introducer sheath (14Fr), which also gives an option of full retrievability in case of complex anatomy. The delivery system is user-friendly and has high flexion. Though the safety and effectiveness of next-generation Myval is well established, this is the first randomized head-to-head trial comparing the Myval series to commercially available TAVI valves (including balloon-expandable Sapien valve). Notably, this is the first randomized trial that will report a 30-day composite endpoint based on the Valve Academic Research Consortium-3 consensus.

PLEASE LIST THE DEVICE(S)/TECHNOLOGY(IES) INVOLVED IN THIS TRIAL

Myval: Myval and Myval Octacor (Meril Life Sciences Pvt. Ltd.) Evolut: Evolut R, Evolut PRO, Evolut PRO+, Evolut FX (Medtronic) Sapien: Sapien 3, Sapien 3 Ultra (Edwards Lifesciences)