TOPLINE:

Patients who have heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and higher serum magnesium levels at baseline were linked to a higher risk for cardiovascular death or HF hospitalization than those on placebo. Empagliflozin treatment was associated with increased serum magnesium levels within 4 weeks and lower risk for cardiac events among those with higher baseline magnesium levels.

METHODOLOGY:

• Researchers conducted a post hoc analysis of a randomized double-blind trial (EMPEROR-Preserved) to explore patterns of serum magnesium levels and effects of the SGLT2 inhibitor empagliflozin in patients with HFmrEF/HFpEF.
• They included 5988 adults with chronic HF (New York Heart Association functional class II-IV; left ventricular EF > 40%) from 622 sites in 23 countries. The mean age of patients ranged from 70.8 to 74.2 years, and about half were male.
• Patients had been randomly assigned to receive either placebo or empagliflozin 10 mg once daily, on top of usual care.
• Serum magnesium levels were measured at baseline; week 4; weeks 12, 32, and 52; and every 24 weeks thereafter. The baseline levels were classified into quintiles (Q1 lowest to Q5 highest), with Q3 (middle quintile) being the reference in placebo comparisons.
• The primary endpoint was a composite of the time to first cardiovascular death or hospitalization for HF, assessed over a median follow-up duration of 26.2 months.

TAKEAWAY:

• Patients on placebo with the highest serum magnesium levels (Q5) had a 44% higher risk for the primary endpoint than those with middle-range (Q3) levels (adjusted hazard ratio, 1.44; P = .010).
• Patients on empagliflozin with higher serum magnesium levels at baseline had a lower risk for the primary endpoint than those on placebo, with Q5 showing a 40% lower risk; hazard ratios declined from Q1 to Q5 (interaction P trend = .030).
• By week 4, patients on empagliflozin had serum magnesium levels about 0.05 mmol/L higher than those on placebo, and this increase persisted. The odds of magnesium levels below 0.75 mmol/L were about 70% lower, and the odds of levels above 0.90 mmol/L were more than threefold higher (P < .001 for both).
• Patients with higher serum magnesium levels were older and had lower estimated glomerular filtration rates and atrial fibrillation more often. Those with lower magnesium levels had a higher prevalence of diabetes and more frequent use of thiazide diuretics.

IN PRACTICE:

“Having higher serum magnesium levels does not seem to be problematic in HFmrEF/HFpEF as long as patients are treated with an SGLT2 inhibitor,” the researchers of the study wrote.

“Given the overall cardiovascular and kidney benefits of SGLT2 inhibitors in the primary trial outcomes of the EMPEROR-Reduced and EMPEROR-Preserved trials — as well as many other large, randomized trials — the baseline serum magnesium level should not currently influence the decision to start an SGLT2 inhibitor among patients with HFrEF [heart failure with reduced ejection fraction] or HFmrEF/HFpEF,” experts wrote in an editorial comment.

SOURCE:

The study was led by João Pedro Ferreira, MD, PhD, University of Porto, Porto, Portugal. It was published online on January 8 in JACC: Heart Failure.

LIMITATIONS:

This was a post hoc analysis; thus, some findings — especially the magnesium-by-treatment pattern — may have occurred by chance. The associations may have been influenced by confounding and did not indicate cause-effect relationships. The study measured only serum magnesium, not intracellular levels.

DISCLOSURES:

The study was sponsored by Boehringer Ingelheim and Eli Lilly and Company. The trial was designed by academic members and representatives of Boehringer Ingelheim. One author reported receiving research support, and another author reported receiving consulting or speaker fees from several companies, including Boehringer Ingelheim, AstraZeneca, and Novartis.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.