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. 2025 Oct 6.
doi: 10.1007/s40256-025-00770-9. Online ahead of print.

Early SGLT2i Therapy Facilitates In-Hospital ARNI Introduction Improving 6-Month Systolic Function in Patients with HFrEF

Andrea D'Amato #  1 , Silvia Prosperi #  1 , Federico Ferranti  1 , Claudia Cestiè  1 , Vincenzo Myftari  1 , Rosanna Germanò  1 , Camilla Segato  1 , Matteo Aulicino  1 , Stefanie Marek-Iannucci  1 , Giovanna Manzi  1 , Domenico Filomena  1 , Marco Valerio Mariani  1 , Lucia Ilaria Birtolo  1 , Silvia Papa  1 , Massimo Mancone  1 , Viviana Maestrini  1 , Roberto Badagliacca  1 , Carmine Dario Vizza  1 , Paolo Severino  2
Affiliations

Early SGLT2i Therapy Facilitates In-Hospital ARNI Introduction Improving 6-Month Systolic Function in Patients with HFrEF

Andrea D'Amato et al. Am J Cardiovasc Drugs. .

Abstract

Purpose: Heart failure with reduced ejection fraction (HFrEF) represents a complex clinical syndrome requiring the timely initiation of disease-modifying therapies. However, the optimal timing for introducing these therapies in the hospital setting remains an area of investigation. This study aims to evaluate whether the early in-hospital initiation of sodium-glucose co-transporter 2 inhibitors (SGLT2i) facilitates the introduction of angiotensin receptor-neprilysin inhibitors (ARNI) during hospitalization and whether this strategy is associated with improved left ventricular systolic function at 6-month follow-up.

Methods: In this prospective, observational, single-centre study, consecutive patients with HFrEF were enrolled and divided into two groups on the basis of the timing of SGLT2i initiation: Group 1 (in-hospital) and Group 2 (post-discharge). The differences in terms of ARNI introduction within hospitalization were evaluated in the two groups. Changes in echocardiographic parameters (left ventricular ejection fraction [LVEF], left ventricular end-diastolic volume [LVEDV], left ventricular end-systolic volume [LVESV], E/e' ratio) at 6-month follow up have been compared among patients treated with ARNI+SGLT2i and SGLT2i alone.

Results: A total of 285 patients were enrolled, 151 for G1 and 134 for G2. Early in-hospital use of SGLT2i was an independent predictor of ARNI initiation before discharge (odds ratio, OR: 3.31; 95% confidence intervals, CI 1.87-5.84; p < 0.001). Among the 89 patients of G1 who completed 6 months of follow-up, early in-hospital therapy with SGLT2i and ARNI represents an independent significant predictor of LVEF > 10% improvement, compared with those treated with SGLT2i alone (OR: 5.353; 95% CI 1.504-12.070; p < 0.003).

Conclusions: Early in-hospital initiation of SGLT2i in patients with HFrEF is associated with a higher likelihood of in-hospital ARNI introduction and with significant improvements in left ventricular systolic function at 6-month follow-up.

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Conflict of interest statement

Declarations. Conflicts of Interest: Andrea D’Amato, Silvia Prosperi, Federico Ferranti, Claudia Cestiè, Vincenzo Myftari, Rosanna Germanò, Camilla Segato, Matteo Aulicino, Stefanie Marek-Iannucci, Giovanna Manzi, Domenico Filomena, Marco Valerio Mariani, Lucia Ilaria Birtolo, Silvia Papa, Massimo Mancone, Viviana Maestrini, Roberto Badagliacca, Carmine Dario Vizza and Paolo Severino declare no conflicts of interest or competing interests. Ethics Approval: Not applicable. Consent to Participate: All the authors participated in the study and made significant intellectual contributions to the manuscript. Consent for Publication: The manuscript is not currently under consideration elsewhere, and the work reported will not be submitted for publication elsewhere until a final decision has been made as to its acceptability by the journal. Availability of Data and Material: Not applicable. Code Availability: Not applicable. Author Contributions: A.D., S.P. and P.S. conceptualized the study; A.D., S.P., F.F., C.C., V.M., R.G., C.S., M.A. and P.S. performed data curation; A.D., S.P., P.S. and M.V.M. conducted the formal analysis and performed the methodology; M.M., V.M., R.B., C.D.V. and P.S. supervised the study and performed validation and visualization; A.D., S.P., F.F., C.C., V.M., R.G., C.S., M.A., S.M.I., G.M., D.F., M.V.M., L.I.B. and S.P. performed writing—original draft and writing—review and editing. All authors have read and agreed to the published version of the manuscript.

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