Empagliflozin reduces the risk of a broad spectrum of heart failure outcomes regardless of heart failure status at baseline

In the EMPA-REG OUTCOME trial (NCT01131676), empagliflozin reduced the primary composite outcome of cardiovascular mortality (CVM), non-fatal myocardial infarction, or non-fatal stroke, driven by a reduction in CVM, as compared to placebo in patients with type 2 diabetes and established cardiovascular disease. These results led to the first approval of a glucose-lowering drug for cardiovascular death prevention. Furthermore, hospitalization for heart failure (HHF) [4.1% vs. 2.7%, hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.50–0.85], and the composite of HHF and CVM (8.5% vs. 5.7%, HR 0.66, 95% CI 0.55–0.79) were pronouncedly reduced,1 with similar effect in those with and without heart failure (HF) at baseline (interaction P> 0.05).2 Subsequent analyses of those without HF at baseline revealed consistent effects of empagliflozin on HF outcomes across the spectrum of HF risk,3 suggesting that empagliflozin reduced not only HHF but also prevented new-onset HF. In addition to adjudicated HF outcomes (HHF, and HHF or CVM), investigatorreported HF and first introduction of loop diuretics were reduced by empagliflozin in the overall study population.2 However, the study of these additional outcomes in patients with and without HF has not yet been explored. The potential interest of the study of these subpopulations is to explore whether empagliflozin may be helpful not only in treating HF, but also in preventing new-onset HF. In the CANVAS Program (Canagliflozin Cardiovascular Assessment Study), canagliflozin [a sodium–glucose co-transporter 2 (SGLT2) inhibitor] also reduced HHF and the composite of HHF or CVM.4 In the DECLARE-TIMI 58 (Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes) trial, dapagliflozin (another SGLT2 inhibitor) also reduced HHF and the composite of HHF or CVM.5 A meta-analysis combining the results from these three trials showed similar effects on HHF or CVM in those with or without HF.6