Abstract
BACKGROUND: In recent heart failure (HF) trials, the win ratio statistical approach, developed to address the limitations of conventional methods, has been increasingly applied to better capture clinical benefits. The TOPCAT study was a randomised controlled trial designed to evaluate the efficacy of spironolactone in patients with HF and a left ventricular ejection fraction (LVEF) ≥45%. This study evaluated the cardiovascular benefits of spironolactone according to their clinical importance using the win ratio method. METHODS: A post hoc analysis was conducted using data from the TOPCAT Americas cohort. The primary outcome was a hierarchical composite comprising the time to cardiovascular death, time to first aborted cardiac arrest, time to first hospitalisation for HF, time to first hospitalisation for arrhythmia and change in the Kansas City Cardiomyopathy Questionnaire Overall summary score at 36 months. Outcomes were analysed using the win ratio statistical model. RESULTS: In all, 1,767 patients were included; 886 were assigned to receive spironolactone and 881 to receive placebo. Hierarchical analysis of the primary composite outcome revealed a significant higher probability of win (28.3%) compared to loss (23.1%) in the spironolactone group, yielding a win ratio of 1.22 (95% CI [1.05-1.42]; p=0.008) and a net clinical benefit (win difference) of 5.2% (95% CI [1.36-9.04]). Detailed assessment of the win differences revealed a concordant positive benefit (win difference >0) across all components of the outcome hierarchy. Subgroup analyses indicated no significant effect of age (<75 years versus ≥75 years), sex (male versus female) or LVEF (<50% versus ≥50%) on the efficacy of spironolactone (p for interaction>0.05). CONCLUSION: This post hoc analysis, using a novel statistical approach, demonstrates the consistent benefits of spironolactone across adverse cardiovascular events, patient symptoms, functional status and quality of life in individuals with HF and mildly reduced or preserved LVEF.