Win Ratio Analysis of the REVERSE Cardiac Resynchronization Trial.

Background: The novel win ratio (WR) statistic has emerged as a promising alternative endpoint for the comparison of two treatment groups on multiple endpoints simultaneously, but it has not been used for cardiac resynchronization therapy (CRT) trials. REVERSE was the first multicenter, randomized CRT trial in mild heart failure (HF). The primary result was a non-significant reduction in the proportion of CRT patients with worsened Clinical Composite Score (CCS) compared to control. However, CRT did improve reverse remodeling measures and delayed time to first HF hospitalizations.

Objective: To demonstrate the value of the WR for the evaluation of CRT using data from REVERSE.

Methods: Individual patient data were analyzed using the WR on a hierarchical endpoint at 12 months that included the CCS components: all-cause death, HF hospitalization, crossover or exit due to HF, change in NYHA class from baseline, and the Patient Global Assessment. All pairs of a CRT and a control patient were compared. The WR is the number of CRT wins divided by the number of losses. Reverse remodeling and Quality of Life were assessed in alternative endpoints.

Results: REVERSE included 610 patients randomized between treatment (CRT ON, n=419) and control (CRT OFF, n=191). Comparison of all 80,029 treatment/control pairs resulted in 53.5% wins, 36.9% losses and 9.5% ties. The WR was 1.45 (95% CI:1.17-1.80) showing CRT superiority (p=0.0009).

Conclusions: Win ratio analysis confirms the benefits of CRT beyond a single primary endpoint and holds promise for analysis of combined endpoints in CRT and other arrhythmia studies.