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

Abstract

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 randomised-controlled trials (RCTs). There is a lack of data reflecting HFrEF patient outcomes in relation to SGLT2i treatment in a real-world environment. Methods: The ongoing H2-registry, initiated in 2021, collects real-world data on hospitalised HF patients in Germany. We analysed 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). However, in multivariate analyses, only MRA treatment was independently associated with reduced mortality risk during FU (HR [95% CI] 0.41 [0.23–0.74]; p = 0.003). In a sub-cohort of patients being continuously treated with an SGLT2i during FU, the observed effect of SGLT2i was more pronounced (unadjusted HR [95% CI] 0.46 [0.28–0.77], p = 0.0023), and continuous SGLT2i treatment was significantly associated with lower all-cause mortality in multivariate analyses (adjusted HR [95% CI] 0.54 [0.30–0.99], p = 0.046). Conclusion: In this prospective German HF registry, SGLT2i treatment was significantly associated with reduced all-cause mortality in HFrEF patients only with continuous use during FU. Treatment with MRA was independently associated with lower all-cause mortality in all performed analyses. These findings add to the available body of evidence regarding the real-world effectiveness of SGLT2i in HFrEF. Trial registration: NCT04844944.