Characteristics and outcomes of patients with heart failure and reduced left ventricular ejection fraction in relation to sodium-glucose cotransporter-2 inhibitor treatment: data from the H2-registry

J. Leiner (Leipzig)¹, S. Hohenstein (Leipzig)², S. König (Leipzig)³, S. Kwast (Leipzig)⁴, A. Nitsche (Leipzig)⁴, M. Seyfarth (Wuppertal)⁵, H. Baberg (Berlin)⁶, A. Lauten (Erfurt)⁷, H. Neuser (Plauen)⁸, A. Staudt (Schwerin)⁹, J. Tebbenjohanns (Hildesheim)¹⁰, R. Andrié (Siegburg)¹¹, M. Niehaus (Gifhorn)¹², M. Ferrari (Wiesbaden)¹³, M. Müller (Hamburg)¹⁴, N. Schulte (Hamburg)¹⁵, K. Bode (Leipzig)³, R. Kuhlen (Bad Homburg)¹⁶, A. Bollmann (Leipzig)^3
1Herzzentrum Leipzig - Universitätsklinik für Kardiologie Abteilung für Rhythmologie Leipzig, Deutschland; ²Herzzentrum Leipzig - Universität Leipzig Leipzig Heart Institute Leipzig, Deutschland; ³Herzzentrum Leipzig - Universität Leipzig Rhythmologie Leipzig, Deutschland; ⁴Helios Health Institute GmbH Leipzig, Deutschland; ⁵Helios Universitätsklinikum Wuppertal - Herzzentrum Medizinische Klinik 3 - Kardiologie Wuppertal, Deutschland; ⁶HELIOS Klinikum Berlin-Buch Herz-Rhythmus-Zentrum Berlin/Brandenburg - Kardiologie Berlin, Deutschland; ⁷Helios-Klinikum Erfurt 3. Medizinische Klinik – Kardiologie Erfurt, Deutschland; ⁸HELIOS Vogtland-Klinikum Plauen Klinik für Innere Medizin II Plauen, Deutschland; ⁹HELIOS Kliniken Schwerin Klinik für Kardiologie und Angiologie Schwerin, Deutschland; ¹⁰Helios Klinikum Hildesheim GmbH Med. Klinik I Hildesheim, Deutschland; ¹¹Helios Klinikum Siegburg Herzzentrum Siegburg, Klinik für Kardiologie, Angiologie Siegburg, Deutschland; ¹²Helios Klinikum Gifhorn GmbH Medizinische Klinik I, Kardiologie Gifhorn, Deutschland; ¹³HELIOS Dr. Horst Schmidt Kliniken GmbH Innere Medizin I Wiesbaden, Deutschland; ¹⁴AstraZeneca GmbH Medical Deparment Hamburg, Deutschland; ¹⁵AstraZeneca Medizinische Abteilung, BioPharmaceuticals Medical Hamburg, Deutschland; ¹⁶Fresenius SE & Co. KGaA Bad Homburg, Deutschland

Background: Heart failure (HF), including heart failure with reduced ejection fraction (HFrEF), remains a major public health issue with increasing disease burden. Recent advances, particularly data on sodium-glucose cotransporter-2 inhibitors (SGLT2i), have shifted HFrEF treatment paradigms based on strong evidence from randomized-controlled trials (RCTs). There is a lack of data reflecting HFrEF patient outcomes in relation to SGTL2i treatment in a real-world environment.

Methods: The ongoing H²-registry, initiated in 2021, collects real-world data on hospitalized HF patients in Germany. We analyzed HFrEF patients (left ventricular ejection fraction, LVEF ≤40%) enrolled until 30-11-2024, stratified by SGLT2i treatment status at index hospital discharge and during follow-up (FU). We assessed baseline characteristics, predictors of SGLT2i use, and 12-month outcomes.

Results: Of 810 HFrEF patients (513 SGLT2i, 297 no-SGLT2i), the median age was 70 years, and 23% were female. Baseline characteristics were comparable between groups. Median LVEF was 30%, and 39% had type 2 diabetes. Use of renin-angiotensin-aldosterone system inhibitors, beta-blockers and mineralocorticoid receptor antagonists (MRA) was more common in the SGLT2i group. Patients treated with SGLT2i at baseline had significantly lower all-cause mortality during FU in unadjusted time-to-event analyses (HR [95%CI] 0.53 [0.33-0.88]; p=0.012). In a sub-cohort of patients being continuously treated with an SGLT2i during FU, the observed effect on all-cause mortality was more pronounced and robustly demonstrated in multivariate analyses (HR [95%CI] 0.79 [0.64-0.98], p=0.028). MRA treatment at baseline was independently associated with reduced mortality risk during FU.

Conclusion: In this prospective German HF registry, SGLT2i treatment was significantly associated with reduced all-cause mortality in HFrEF patients, especially with continuous use during FU. These findings support the real-world effectiveness of SGLT2i in improving HFrEF outcomes. Trial registration number: NCT04844944