Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved

Figures

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  Fig. 1. Effect of empagliflozin versus placebo on time-to-first-event outcomes and total heart failure hospitalizations by LVEF category. Hazard ratios for the primary endpoint, first hospitalization for heart failure (HHF), cardiovascular (CV) death and all-cause mortality were calculated using a multivariable Cox regression model, whereas the hazard ratio for total HHF was calculated using a joint frailty model with CV death as competing risk, as described in the Methods. Data are presented as point estimates and 95% CIs with two-sided P values. No adjustments for multiple testing were made.

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  Fig. 2. Comparison of effects of empagliflozin versus placebo on outcomes by LVEF category. Effects are shown for the primary outcome (cardiovascular death or hospitalization for heart failure) (a), first hospitalization for heart failure (b), cardiovascular death (c) and total hospitalizations for heart failure (d). Detailed results for all related modeled analyses are shown in Fig. 1.

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  Fig. 3. Comparison of empagliflozin versus placebo for change in eGFR over time and eGFR slope by LVEF category. Effects are shown for LVEF ≥ 50% (a) and LVEF 41–49% (b). a, Between-group difference in slope: 1.24 ml min−1 1.73 m−2 per year (95% CI: 0.87–1.61, P < 0.0001). b, Between-group difference in slope: 1.61 ml min−1 1.73 m−2 per year (95% CI: 1.09–2.13, P < 0.0001). Data are presented as adjusted mean and standard error. Change in eGFR was analyzed using a mixed model for repeated measures while the eGFR slope (that is, the rate of change in the decrease in eGFR) was analyzed using a random coefficient model, as described in the Methods.

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  Fig. 4. Comparison of empagliflozin versus placebo for outcomes by LVEF subgroups in patients with LVEF ≥ 50%. Effects are shown for the first event of cardiovascular (CV) death or hospitalization for heart failure (HHF), first HHF, CV death and total HHF (a), and the slope of change in eGFR (b) for patients in subgroups of LVEF from 50% to 70%. Data for the clinical events are presented as point estimates and 95% confidence intervals (CIs); data for the difference in slope of eGFR are presented as mean values and 95% CIs.

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  Extended Data Fig. 1. Effect of empagliflozin versus placebo on changes in NYHA functional class in patients with LVEF ≥ 50%. Odds ratios were calculated using a multivariable Cox regression model. Data are presented as point estimates and 95% CIs with two-sided P values. No adjustments for multiple testing were made. Patients treated with empagliflozin had higher odds of improving NYHA class at week 52 (odds ratio 1.32 [95% CI: 1.10–1.56]; P = 0.0033) and lower odds of worsening NYHA class at week 52 (odds ratio 0.74 [95% CI: 0.54–1.01]; P = 0.0606). LVEF, left ventricular ejection fraction; NYHA, New York Heart Association.

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  Extended Data Fig. 2. The effect of different heart failure therapies tested in specific trials aiming to recruit HFpEF patients. Known and estimated treatment effects for the composite endpoint of the time to a first event of cardiovascular death or HHF are displayed for the subgroup of patients with LVEF ≥ 50%. Panel A shows treatment effect sizes, and Panel B provide hazard ratios and event rates as are available. CI, confidence interval; CV, cardiovascular; HF, heart failure; HHF, hospitalization for heart failure; HR, hazard ratio; LVEF, left ventricular ejection fraction.