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Aims We investigated the incremental advantage in terms of N-terminal pro-B-type natriuretic peptide (NT-proBNP) reduction in patients affected by heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (S/V) and mineralocorticoid receptor antagonists (MRA) versus patients treated with S/V only.Methods Consecutive adult patients with a left ventricular ejection fraction (LVEF) of ≤40% who were followed in our outpatient clinic from January 2016 to December 2019 and treated with S/V were analysed.Results Out of eligible 147 patients, 99 were treated with S/V+MRA at baseline and 48 patients were treated with S/V. Patients treated with S/V+MRA were significantly younger (61.5 vs 67.8 years, p=0.006), had better basal renal function (serum creatinine 1.2 vs 1.4 mg/dL, p=0.006) and lower LVEF (30.9% vs 33.1%, p=0.039). At follow-up at 8–16 months, 84 out of 99 patients continued to be on S/V+MRA, and 39 out of 48 patients continued to be on S/V. Between these two groups, at follow-up, LVEF did not vary significantly, ΔNT-proBNP was not significantly different (−215.7 vs −165.9 pg/mL, p=0.93) and neither was the rate of hospitalisation for heart failure (9.5% vs 12.8%, p=0.58). Using general linear models, both age and basal NT-proBNP influenced significantly ΔNT-proBNP (respectively, p=0.002; p=0.005), while treatment with S/V+MRA versus S/V only did not significantly influence ΔNT-proBNP (p=0.462).Conclusion Even with the limitations of a small retrospective study, our results generate the hypothesis that MRA might not provide any additional value in patients with HFrEF treated with S/V. Larger studies are needed to test if MRA should remain a standard treatment in patients with HFrEF treated with S/V.