Association of over-the-counter magnesium supplementation with heart failure-related clinical worsening in heart failure with preserved ejection fraction

Background

Heart failure with preserved ejection fraction (HFpEF) remains associated with a high burden of clinical deterioration despite contemporary guideline-directed therapy. Magnesium plays an important role in myocardial electrophysiology and vascular function; however, data on the clinical impact of over-the-counter magnesium supplementation in HFpEF are scarce.

Purpose

To evaluate the association between over-the-counter magnesium supplementation and heart failure–related clinical worsening in patients with HFpEF.

Methods

This single-centre, prospective observational study included patients with HFpEF. Forty-seven patients receiving over-the-counter magnesium supplementation were compared with 186 patients not receiving magnesium. To minimise baseline differences, propensity score matching (1:1) was performed using clinically relevant baseline parameters. After matching, 37 patients were included in each group with well-balanced baseline characteristics.

The primary endpoint was heart failure–related clinical worsening, defined as a composite of heart failure hospitalisation or the need for outpatient diuretic dose escalation. Time-to-event analyses were performed using Cox proportional hazards models.

Results

Median follow-up duration was 260 (233–286) days. After propensity score matching, heart failure–related clinical worsening occurred less frequently in patients receiving magnesium supplementation compared with those not receiving magnesium (21.6% vs 45.9%, p=0.026). In Cox regression analysis, magnesium supplementation was associated with a significantly lower risk of the primary endpoint (hazard ratio 0.41, 95% confidence interval 0.17–0.99; p=0.039). New-onset atrial fibrillation occurred less frequently in the magnesium group (8.1% vs 24.3%), although this difference did not reach statistical significance (p=0.058). Cardiovascular mortality was similar between groups (8.1% vs 13.5%, p=0.452).

Conclusion(s)

In this prospective, propensity score–matched study, over-the-counter magnesium supplementation was associated with a lower risk of heart failure–related clinical worsening in patients with HFpEF. No significant difference in cardiovascular mortality was observed, while a trend towards reduced new-onset atrial fibrillation was noted. These findings are hypothesis-generating and support further investigation in larger, randomised studies.The baseline characteristics of patientsFor image description, please refer to the figure legend and surrounding text.Effects of magnesium on HF worseningFor image description, please refer to the figure legend and surrounding text.