Early outcomes of a randomized non-inferiority trial comparing TAVI devices: the LANDMARK trial

Published in Congress: Euro PCR 2024

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 Dr. Yusuf Bozkurt Şahin

Background:
Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to surgical intervention in high surgical risk patients. The SAPIEN and Evolut transcatheter heart valves (THVs) series provided the main evidence for TAVR and positioned these 2 THVs as the contemporary standards. The Myval series are new balloon-expandable THVs that have shown favorable results in observational studies. The safety and efficacy of these new technologies should be investigated against contemporary TAVR devices in randomized controlled trials.

Objective:
The aim of the LANDMARK study was to compare the balloon-expandable THV series with the contemporary THV series (SAPIEN THV and Evolut THV series) in patients with severe symptomatic aortic stenosis.

Methods:
It is a prospective, multinational, multicenter, randomized, open-label and non-inferiority study. A total of 768 patients from 31 centers in 16 countries were included in the study.  Patients were randomized 1:1 to Myval and contemporary THV (SAPIEN and Evolut). The mean age was 80 years. Gender, body mass index and symptoms were similar in both groups. The two groups were similar in terms of STS risk score and the majority of patients were low risk (STS risk score <4) (76% in the Myval group and 75% in the contemporary device arm).
The primary endpoint was all-cause death, all stroke, bleeding (varc 3-4), acute kidney injury (stages 2-4), major vascular complications, moderate or severe prosthetic valve regurgitation, conduction system disorders requiring permanent pacemaker implantation at 30-day follow-up.

Results:
A total of 768 patients were randomized 1:1 to implantation of Myval THV or an alternative contemporary TAVR device. At 30 days, the primary endpoint was met in 24.7% and 27.6% in the Myval and contemporary valves arms, respectively, demonstrating that Myval was non-inferior (p<0-0001 for non-inferiority). There were no significant differences in any component of the primary endpoint, and no differences in technical and device success (defined according to VARC-3 criteria). Secondary endpoints, including pacemaker implantation rates and improvements in hemodynamic parameters (mean pressure gradient and effective orifice area) were also similar in both study arms.

Conclusion:
Early outcomes from the LANDMARK study demonstrate that the Myval THV series is noninferior to contemporary THV series in terms of early safety and efficacy composite endpoints (all-cause death, all stroke, bleeding types 3 and 4, acute kidney injury grades 2-4, moderate or severe prosthetic valve regurgitation, new permanent pacemaker implantation and major vascular complication) at 30 days.

Interpretations: 
The LANDMARK study expanded the indications for TAVR to patients with complex anatomy, such as small annulus (<430 mm2, 31.9%) and bicuspid aortic valves (6.8%). The Myval THV is available in intermediate valve sizes, which increases the possibility of selecting the appropriate valve according to the patient. In the study, intermediate valve sizes were used in 48% of patients. When comparing the EOA of conventional nominal THV sizes (20, 23, 26 and 29 mm), the Myval series showed equal (20 mm) or significantly greater EOA than the Sapien series (23, 26 and 29 mm) and similar EOA to the Evolut series (26 and 29 mm). Whether the documented EOA of the Myval THV series will have a beneficial impact on long-term patient prognosis and valve durability will be revealed by follow-up for up to 10 years.