Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial

Background: In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF. / Methods and Results: We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31–1.17], 0.79 [0.51–1.23], and 0.63 [0.50–0.78], respectively; P interaction = 0.62). / Conclusions: In EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF

Cardiovascular Benefit of Empagliflozin Across the Spectrum of Cardiovascular Risk Factor Control in the EMPA-REG OUTCOME Trial

ContextControl of multiple cardiovascular (CV) risk factors reduces CV events in individuals with type 2 diabetes.ObjectiveTo investigate this association in a contemporary clinical trial population, including how CV risk factor control affects the CV benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor.DesignPost hoc analysis.SettingRandomized CV outcome trial (EMPA-REG OUTCOME).ParticipantsType 2 diabetes patients with established CV disease.InterventionEmpagliflozin or placebo.Main Outcome MeasuresRisk of CV outcomes—including the treatment effect of empagliflozin—by achieving 7 goals for CV risk factor control at baseline: (1) glycated hemoglobin ResultsIn the placebo group, the hazard ratio (HR) for CV death was 4.00 (95% CI, 2.26–7.11) and 2.48 (95% CI, 1.52–4.06) for patients achieving only 0–3 or 4–5 risk factor goals at baseline, respectively, compared with those achieving 6–7 goals. Participants achieving 0–3 or 4–5 goals also had increased risk for the composite outcome of hospitalization for heart failure or CV death (excluding fatal stroke) (HR 2.89 [1.82–4.57] and 1.90 [1.31–2.78], respectively) and 3-point major adverse CV events (HR 2.21 [1.53–3.19] and 1.42 [1.06–1.89]). Empagliflozin significantly reduced these outcomes across all risk factor control categories (P > 0.05 for treatment-by-subgroup interactions).ConclusionsCardiovascular risk in EMPA-REG OUTCOME was inversely associated with baseline CV risk factor control. Empagliflozin’s cardioprotective effect was consistent regardless of multiple baseline risk factor control.</div