Abstract 15893: Mediators of the Improvement in Heart Failure Outcomes With Empagliflozin in the EMPA-REG OUTCOME Trial

Introduction: In the EMPA-REG OUTCOME trial, empagliflozin (EMPA) given in addition to standard of care to patients with T2DM and established CV disease reduced the risk of hospitalization for heart failure (HHF) or death from HF by 39% vs placebo (hazard ratio [HR] 0.61 [95% CI 0.47, 0.79]; pu003c0.001). This exploratory mediation analysis assessed the extent to which changes in individual covariates during the trial contributed to the reduction in HHF or death from heart failure (HF) with empagliflozin. Methods: Potential mediators were identified post-hoc. Effects of each covariate on the HR for the composite of HHF or death from HF with empagliflozin vs placebo were analyzed using Cox regression models with treatment group adjusted for the baseline value of the covariate and the change from baseline in the covariate or the updated mean of the covariate (considering all prior values), each as a time-dependent covariate. HRs were then compared to a model without adjustment for covariates. Results: Changes i...