Article Dans Une Revue JACC: Heart Failure Année : 2025

Serum Magnesium and the Effect of Empagliflozin in Heart Failure With Reduced Ejection Fraction: findings from EMPEROR-Reduced

Résumé

Background: Magnesium plays a central role in maintaining cellular homeostasis.

Limited data exist on clinical implications of magnesium derangements in heart failure with reduced ejection fraction (HFrEF) and on the influence of SGLT2 inhibitors on serum magnesium levels.

Objectives: Using the EMPEROR-Reduced (NCT03057977) population, we aim to study the association of serum magnesium with outcomes, assess the impact of empagliflozin on serum magnesium levels, and explore the influence of serum magnesium on the effect of empagliflozin on cardiovascular and renal outcomes.

Methods: Patients with HFrEF were randomized to receive placebo or empagliflozin 10 mg/daily. Laboratory results were available at baseline, week 4, and weeks 12, 32, 52, and every 24 weeks thereafter. The median follow-up time was 16 months.

The primary outcome was a composite of cardiovascular death or HF hospitalization.

Results: A total of 3730 patients were included. The mean serum magnesium levels at baseline were 0.83±0.11 mmol/L. The corresponding magnesium quintiles (Q) were: Q1=0.68±0.07 mmol/L (N=878); Q2=0.79±0.02 (N=724); Q3=0.84±0.01 (N=668); Q4=0.88±0.02 (N=733); and Q5=0.97±0.05 (N=727). Patients with higher magnesium levels were older and had lower eGFR. Conversely, patients with lower serum magnesium had diabetes more frequently. Lower magnesium levels were modestly associated with a higher risk of HF and kidney events. The effect of empagliflozin (vs placebo) on the study primary outcome was more pronounced at lower baseline serum magnesium levels: Q1:HR=0.54, 95%CI=0.41-0.71, Q2:HR=0.69, 95%CI=0.50-0.96, Q3:HR=0.82, 95%CI=0.58-1.15, Q4:HR=0.99, 95%CI=0.72-1.37, Q5:HR=0.87, 95%CI=0.65-1.17, interaction P-trend=0.043.

Empagliflozin rapidly increased magnesium levels by 0.05 mmol/L. The relative odds of experiencing lower magnesium levels were reduced with empagliflozin.

Conclusion:

In EMPEROR-Reduced, low serum magnesium levels were associated with poor HF and kidney outcomes. Empagliflozin increased serum magnesium levels and was associated with a more pronounced reduction of HF events among patients with low magnesium levels at baseline.

Fichier principal
Vignette du fichier
EMPEROR_Red_Magnesium_Paper.pdf (554.23 Ko) Télécharger le fichier
EMPEROR_Red_Magnesium_Supplement.pdf (99.28 Ko) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)
Licence

Dates et versions

hal-05347113 , version 1 (04-11-2025)

Licence

Identifiants

Citer

João Pedro Ferreira, Stefan D Anker, Javed Butler, Francisco Vasques-Nóvoa, Pedro Marques, et al.. Serum Magnesium and the Effect of Empagliflozin in Heart Failure With Reduced Ejection Fraction: findings from EMPEROR-Reduced. JACC: Heart Failure, 2025, pp.102751. ⟨10.1016/j.jchf.2025.102751⟩. ⟨hal-05347113⟩
179 Consultations
3 Téléchargements

Altmetric

Partager

  • More