Empagliflozin in heart failure with preserved and mildly reduced ejection fraction: prognostic benefit confirmed with different endpoint definitions
Abstract
A very recent review by Prof. Braunwald told the amazing story of sodium–glucose cotransporter 2 inhibitors (SGLT2i), from the discovery of their glycosuric properties in the late 19th century to the characterization of the mechanism of glycosuria (1980s), the development of the first synthetic SGLT2i (1990s), the evaluation of SGLT2i as antidiabetic drugs, and finally the unexpected finding of their great efficacy in patients with heart failure (HF).1 The emerging paradigm is that SGLT2i are effective across the whole spectrum of HF: indeed, a prognostic benefit from SGLT2i has been observed in patients with chronic HF with reduced ejection fraction (HFrEF) or preserved/mildly reduced ejection fraction (HFmrEF/HFpEF), and also in those with acute HF. The great survival benefit from SGLT2i is likely unrelated to their diuretic effect (which is mild) and also to glycosuria (given their efficacy in both diabetic and non-diabetic patients).1–3 Other positive effects have then been searched, and may include a modulation of cardiac metabolism and the epicardial adipose tissue phenotype, a relief from oxidative stress and inflammation, blunted sympathetic nerve activity, and the induction of a more favourable haemodynamic profile.1 The combination of these effects might explain the survival benefit from SGLT2i even in the challenging scenario of HFpEF,
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