SGLT-2 inhibitors help avert death in patients with HFrEF

Use of SGLT-2 inhibitors may reduce the risk of all-cause and cardiovascular (CV) mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), reports a study.

"These results support the benefits of SGLT-2 inhibitors observed in randomized controlled trials and provide novel and important data on their effectiveness in real-world clinical settings and across key clinical subgroups, including patients with and without diabetes,” the investigators said.

This linked database study searched the national registers in Denmark from July 2020 to June 2023 and identified patients with HF, aged ≥45 years, with left ventricular ejection fraction ≤40 percent. Cox regression was used to estimate hazard ratios (HRs), adjusted using inverse probability of treatment weighting based on propensity scores.

The investigators assessed all-cause mortality comparing initiation and continued use of SGLT-2 inhibitors with continued treatment with other standard-of-care HF drugs and nonuse of SGLT-2 inhibitors. They also evaluated the composite of CV mortality or admission to hospital with HF and its components.

A total of 6,776 patients (mean age 71.2 years, 70 percent male, 20 percent had diabetes) who initiated SGLT-2 inhibitors (79 percent dapagliflozin, 21 percent empagliflozin) and 14,686 patients who remained on standard-of-care HF drugs or did not use SGLT-2 inhibitors were included in the analysis.

During follow-up, 374 SGLT-2 users and 1,602 nonusers died (incidence rate [IR], 5.8 vs 8.5 per 100 person-years), with a weighted HR of 0.75 (95 percent confidence interval [CI], 0.66–0.85) for all-cause mortality and a weighted IR difference of –1.6 per 100 person-years (95 percent CI, –2.5 to –0.8). [BMJ 2024;387:e080925]

Additionally, the weighted HR for CV mortality or hospital admission with HF was 0.94 (95 percent CI, 0.85–1.04). Separately, the weighted HRs for CV mortality and hospital admission with HF were 0.77 (95 percent CI, 0.64–0.92) and 1.03 (95 percent CI, 0.92–1.15), respectively.

In subgroup analysis, the weighted HRs for all-cause mortality were similar between patients with (HR, 0.73, 95 percent CI, 0.58–0.91) and without diabetes (HR, 0.73, 95 percent CI, 0.63–0.85; p=0.99).

Database studies

“To our knowledge, no previous large scale database studies have investigated the effectiveness of SGLT-2 inhibitors on mortality among patients with HFrEF, with or without type 2 diabetes,” the investigators said. 

“The results from our study expand the available evidence through robust analyses of a well characterized set of patients with HF, including information on left ventricular ejection fraction, NYHA class, and renal function,” they added.

The current study also supports previous randomized controlled trials by adding evidence to a broad HF population in routine clinical practice and providing insights into the effectiveness of SGLT-2 inhibitors across diverse patient groups, according to the investigators.

"In terms of clinical impact, the results support current guidelines recommending SGLT-2 inhibitors for all patients with HFrEF,” they added. [Eur Heart J 2021;42:3599-3726; J Am Coll Cardiol 2022;79:1757-1780]