Serum magnesium and outcomes in patients with heart failure and reduced ejection fraction: insights from the GALACTIC-HF trial

Abstract Background The frequency and prognostic significance of abnormalities in serum magnesium levels have not been described in a contemporary HF population. Purpose To evaluate the prognostic significance of serum magnesium levels in patients with heart failure and reduced ejection fraction (HFrEF) enrolled in the GALACTIC-HF trial (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure). Methods GALACTIC-HF was a randomised, double-blind, multicentre, event-driven trial that investigated the efficacy and safety of the cardiac myosin activator omecamtiv mecarbil (OM) compared to placebo in patients with HF and a left ventricular ejection fraction (LVEF) ≤35%. The primary outcome was a time-to-first event analysis of the composite of a worsening HF event (hospitalisation or an urgent visit) or cardiovascular death. The primary analysis was conducted on participants enrolled as outpatients. Results In GALACTIC-HF, baseline magnesium data were available for 8,205 of the 8,232 analysed patients, including 6,147 outpatients. Among outpatients, 1,082 (17.6%) had magnesium levels below 0.75 mmol/L, 4,410 (71.7%) had levels within the normal range, and 655 (10.7%) had levels above 0.95 mmol/L. Patients with hypermagnesaemia had higher NT-proBNP levels and lower systolic BP, and more had an eGFR 45 mL/min/1.73 m² and were in NYHA functional class III/IV, compared to those with normal magnesium levels. In contrast, patients with hypomagnesaemia had higher SBP but similar NT-proBNP levels and a similar proportion with eGFR 45 mL/min/1.73 m², compared to those with normal magnesium levels. LVEF did not differ among the three magnesium groups. The incidence rate (per 100 patient-years) for the primary composite outcome was highest in patients with hypermagnesemia (34.9, 95% CI 31.2 to 39.0); incidence rates were similar in those with hypomagnesaemia (20.9, 95% CI19.9–22.0) and normal magnesium levels (21.5, 95% CI 19.4–23.8). Similar trends were observed for the components of the primary composite outcome, cardiovascular death, and all-cause death. However, the incidence rate of sudden death did not differ among the groups (Figure). The therapeutic benefit of OM compared with placebo on clinical outcomes was not modified by serum magnesium levels at baseline. Analysis of all participants (inpatients and outpatients) gave similar findings. Conclusion In GALACTIC-HF, 10.7% of patients with HFrEF had hypermagnesemia, which was associated with a higher risk of the primary outcome than in people with normal magnesium levels. However, incidence rates of sudden death were similar across all magnesium levels. The effect of OM on clinical outcomes was unaffected by magnesium levels.Incidence rate for clinical outcomes Association between Mg and outcomes