Win ratio analysis of the REVERSE cardiac resynchronization trial.

Abstract

Background: The novel win ratio (WR) statistic has emerged as a promising alternative end point for the comparison of 2 treatment groups on multiple end points simultaneously, but it has not been used for cardiac resynchronization therapy (CRT) trials. The REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE; ClinicalTrials.gov identifier: NCT00271154) 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 compared with 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 end point at 12 months that included the following clinical composite score components: all-cause death, HF hospitalization, crossover or exit because of HF, change in New York Heart Association 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 as alternative end points.

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% confidence interval, 1.17-1.80), showing CRT superiority (P = .0009).

Conclusion: WR analysis confirms the benefits of CRT beyond a single primary end point and holds promise for analysis of combined end points in CRT and other arrhythmia studies.