The effect of malnutrition on the efficacy and safety of empagliflozin: a post hoc analysis of the EMPEROR-Reduced trial

Malnutrition is common among patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with adverse events. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, can lead to loss of glucose and calories, raising concerns for physicians when prescribing SGLT2 therapy to malnourished heart failure patients. However, it remains unclear whether malnutrition affects the efficacy and safety of empagliflozin in this population.

This study aimed to explore the association between malnutrition and adverse cardiovascular events in patients with HFrEF and to assess the impact of malnutrition on the efficacy and safety of empagliflozin in the EMPEROR-Reduced trial.

The risk of malnutrition was assessed at baseline using the validated Controlling Nutritional Status (CONUT) score. Patients were categorized into two groups: "malnutrition" (CONUT ≥2) and "no malnutrition" (CONUT <2). The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure.

A total of 3,676 patients were included in the study, of which 2,039 (55.5%) were identified as malnourished. Over a median follow-up of 14.7 months, 807 primary outcomes were recorded. Patients with malnutrition showed a significantly higher risk of the primary outcome in both the empagliflozin and placebo groups (adjusted hazard ratios of 1.41 [95% confidence interval (CI), 1.13–1.78] and 1.45 [95% CI, 1.19–1.76], respectively). In comparison to placebo, empagliflozin reduced the risk of the primary outcome similarly in patients with and without malnutrition, with hazard ratios (95% CI) of 0.73 (0.58–0.92) and 0.78 (0.65–0.92), respectively (P-interaction = 0.74). Patients treated with empagliflozin had a lower risk of serious adverse events, regardless of their nutritional status.

Malnutrition was a marker of high cardiovascular risk. Patients with malnutrition benefit similarly to other patients from empagliflozin without an increased risk of serious adverse events.