Win ratio analysis of 1-year outcomes after transcatheter aortic valve implantation: substudy of the LANDMARK trial

Abstract Background The LANDMARK trial demonstrated the comparable clinical performance of the Myval balloon-expandable transcatheter heart valve (THV) series with the contemporary THVs – Sapien and Evolut series – at 1 year. The primary analysis was performed based on the conventional time-to-first event analysis. Purpose To perform a win ratio analysis of the 1-year outcomes in the LANDMARK trial, accounting for event severity and recurrent events. Methods This is a substudy of the LANDMARK trial. The LANDMARK trial is a randomized, open-label, multi-center, non-inferiority trial which compares clinical outcomes of the Myval THV series with the contemporary THVs (Sapien and Evolut series). A total of 768 patients with severe symptomatic native aortic stenosis were assigned in a 1:1 ratio either to receive a Myval series (n=368) or a contemporary THV (n=368). Clinical events were adjudicated by an independent committee. A hierarchical composite endpoint was analyzed using the win ratio method with the following order: (1) all-cause death, (2) disabling stroke, (3) non-disabling stroke, and (4) procedure- or valve-related hospitalization. Outcomes were compared across 147,456 (384x384) unmatched patient pairs. Death and stroke were analyzed by time-to-first-event (later = winner), and hospitalization by the total number of events (fewer = winner). An extended analysis included quality-of-life (QoL) outcomes. Results The win ratio for the composite endpoint was 1.02 (95% CI: 0.68–1.51; p=0.94, Figure 1), with 17,870 wins for the novel balloon-expandable valve series and 17,599 for contemporary valve series. Mortality wins were balanced; contemporary valves had numerically more wins for disabling stroke, while the novel balloon-expandable valve had numerically more wins for non-disabling stroke and hospitalization. The extended endpoint including QoL yielded a win ratio of 1.13 (95% CI: 0.82–1.55; p=0.45, Figure 2). Conclusion This win ratio analysis confirmed comparable 1-year hierarchical outcomes between the Myval series and the contemporary valve series, supporting their clinical equivalence.composite endpointFor image description, please refer to the figure legend and surrounding text. extended composite endFor image description, please refer to the figure legend and surrounding text.