Win ratio analysis of the REVERSE cardiac resynchronization trial.

Area of Science:

• Cardiology
• Clinical Trials
• Biostatistics

Background:

• Cardiac resynchronization therapy (CRT) trials often use single endpoints, but the novel win ratio statistic allows simultaneous comparison of multiple endpoints.
• The REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) trial, a multicenter randomized CRT study in mild heart failure (HF), is analyzed.
• Previous primary analysis of REVERSE showed non-significant reduction in worsened clinical composite scores, despite CRT improving remodeling and delaying HF hospitalizations.

Purpose of the Study:

• To evaluate the utility of the win ratio statistic for assessing cardiac resynchronization therapy (CRT) using data from the REVERSE trial.
• To demonstrate the value of the win ratio in analyzing complex outcomes in heart failure (HF) clinical trials.

Main Methods:

• Individual patient data from the REVERSE trial were analyzed using the win ratio statistic.
• A hierarchical endpoint at 12 months included all-cause death, HF hospitalization, crossover/exit due to HF, change in NYHA class, and Patient Global Assessment.
• Win ratio was calculated by comparing all pairs of CRT and control patients (wins/losses).

Main Results:

• The REVERSE trial included 610 patients (419 CRT-ON, 191 CRT-OFF).
• Analysis of 80,029 treatment/control pairs yielded a win ratio of 1.45 (95% CI, 1.17-1.80), indicating CRT superiority (P = .0009).
• The win ratio analysis showed 53.5% wins, 36.9% losses, and 9.5% ties.

Conclusions:

• The win ratio analysis confirms the significant benefits of cardiac resynchronization therapy (CRT) across multiple endpoints in heart failure patients.
• This statistical approach holds promise for evaluating combined endpoints in future CRT and other arrhythmia studies.
• The win ratio provides a robust method for demonstrating treatment efficacy when multiple outcomes are considered.