Association Between Over-the-Counter Magnesium Supplement Use and Health Outcomes in Veterans with Newly Diagnosed Heart Failure.

Over-the-counter magnesium supplement use was associated with significantly better survival outcomes in veterans with newly diagnosed heart failure.

• Primary analysis HR: 0.81 (95% CI: 0.77–0.86), p < 0.0001
• Sensitivity analysis in patients surviving ≥6 months: HR 0.91 (95% CI: 0.85–0.97), p = 0.0025
• Sensitivity analysis in patients with continuous documentation of magnesium supplement use: HR 0.77 (95% CI: 0.72–0.82), p < 0.0001
• The outcome was composite all-cause hospitalization or death

The study enrolled 9900 magnesium supplement users and 9900 matched non-users from the Veterans Health Administration.

• Eligible patients were outpatients who received ambulatory care in the Veterans Health Administration between 1 January 2000 and 31 December 2020
• The weighted cohort had a mean age of 72.6 years, 12.6% African American, and 3.4% women
• Median follow-up was 0.7 years with patients followed for up to five years from the eligible date
• Patients were censored if they changed from the assigned treatment strategy or initiated prescribed magnesium replacement

Natural language processing was used to identify self-reported magnesium supplement use in medical records.

• Initial self-reported magnesium supplement use was measured at the eligible date and identified using natural language processing
• Use was then checked repeatedly to confirm continuous use
• Previous magnesium supplement or replacement use, hospitalization within 30 days prior to eligible date, and end-stage renal disease were exclusion criteria

Inverse probability treatment weighting combined with Cox regression was used to estimate hazard ratios for the association between magnesium supplement use and outcomes.

• Inverse probability treatment weighting (IPTW) was applied to control for confounding
• Cox's regression was used to estimate hazard ratios
• A target trial emulation framework was used to structure the observational study
• Sensitivity analyses were conducted in patients surviving ≥6 months and those with continuous documentation of magnesium supplement use

Individuals with heart failure are at increased risk of magnesium deficiency, yet magnesium supplements are widely used without clear evidence of efficacy in this population.

• Magnesium supplements are widely available over-the-counter
• At the time of the study, there was no clear evidence of efficacy for magnesium supplementation in heart failure
• The study was designed to address this evidence gap using a target trial emulation approach