Win ratio analysis of the REVERSE cardiac resynchronization trial
Michael R Gold1, William T Abraham2, Javed Butler3
1Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.
Insights
The win ratio statistic demonstrates cardiac resynchronization therapy (CRT) superiority in heart failure (HF) patients by analyzing multiple endpoints. This method confirms CRT benefits beyond a single primary outcome.
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.
Background:
The novel win ratio 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. 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 win ratio for the evaluation of CRT using data from REVERSE.
Methods:
Individual patient data were analyzed using the win ratio 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 win ratio 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 win ratio was 1.45 (95% confidence interval, 1.17-1.80), showing CRT superiority (P = .0009).
Conclusion:
Win ratio 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.
