One-year outcomes of novel balloon-expandable versus contemporary transcatheter heart valves in severe aortic stenosis: the LANDMARK trial

Abstract

Background In the LANDMARK trial, the Myval balloon-expandable transcatheter heart valve (THV) series was non-inferior to the most commonly used contemporary Sapien and Evolut Series THVs for the 30-day early safety endpoint in participants with symptomatic severe native aortic stenosis (AS). Objectives The current study reports clinical outcomes, hemodynamic performances and quality of life (QOL) at one year. Methods This open-label, non-inferiority trial enrolled 768 participants across 31 hospitals in Europe, New Zealand and Brazil. Participants were randomly assigned (1:1) to receive either a Myval THV series or a contemporary THV (Sapien or Evolut series). The composite endpoint at one year included all-cause mortality, all strokes, and procedure- or valve-related hospitalizations. Clinical efficacy was defined as freedom from the composite endpoint. As recommended in Valve Academic Research Consortium (VARC)-3, the above composite endpoint, combined with the assessment of QOL at baseline and 1 year with the Short Form-12, was reported as an extended composite endpoint. The non-inferiority hypothesis was prespecified for the assessment of the primary endpoint at 30 days. Considering the specific 1-year composite endpoints of VARC-3 and the event rate of 27.23% derived from recent studies, an a posteriori descriptive and exploratory non-inferiority hypothesis was introduced with a non-inferiority margin of 10.89%. The analysis was performed in the intention-to-treat population. Results The mean age was 80 years, 48% were women, and the median Society of Thoracic Surgeons Predicted Risk of Mortality score was 2.6%. There was no significant difference in the Kaplan-Meier estimates of freedom from the composite endpoint at 365 days (Myval THV 87.0% vs. Contemporary THVs 86.9%). The Myval THV series was non-inferior to the contemporary THVs for the composite endpoint (difference: -0.1%, one-sided 95% confidence interval: 3.9%, Pnon-inferiority < 0.0001). Similarly, there were no significant differences in freedom from the extended composite endpoint (80.5% vs 77.3%, difference: 3.2%, 95% CI: -2.9 to 9.2%, p=0.33). Conclusions In the treatment of symptomatic severe native AS, the clinical and hemodynamic outcomes of the Myval THV series were comparable to those of contemporary THVs for the 1-year composite of all-cause mortality, all strokes, or procedure- or valve-related hospitalizations.