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

Abstract Background and Aims The frequency and prognostic significance of abnormalities in serum magnesium concentrations have not been described in a contemporary heart failure (HF) population. The authors evaluated the prognostic significance of magnesium concentrations in patients with HF with reduced ejection fraction (HFrEF) enrolled in GALACTIC-HF trial. Methods GALACTIC-HF was a randomized, double-blind, multicentre, event-driven trial that investigated the efficacy and safety of omecamtiv mecarbil compared with placebo in HF patients with left ventricular ejection fraction ≤ 35%. The primary outcome was the composite of a first worsening HF event or cardiovascular death. Results A total of 6147 outpatients had baseline serum magnesium data. Of these, 1082 (17.6%) had magnesium concentrations below .75 mmol/L, 4410 (71.7%) had concentrations within the normal range, and 655 (10.7%) had concentrations above .95 mmol/L. The incidence rate (per 100 person-years) for the primary composite outcome was highest in patients with hypermagnesaemia (34.9, 95% confidence interval 31.2–39.0), while rates were similar between those with hypomagnesaemia (21.5, 19.4–23.8), and normal magnesium (20.9, 19.9–22.0). Similar trends were observed for the components of the primary outcome and all-cause death. The incidence rate of sudden death and ventricular tachyarrhythmia did not differ among the three magnesium groups, but the risk of death from worsening HF was highest in patients with hypermagnesaemia. Conclusions In GALACTIC-HF, 10.7% of outpatients with HFrEF had hypermagnesaemia, which was associated with a higher risk of the primary outcome compared with normal magnesium concentrations. Abnormal magnesium levels were not associated with a higher risk of sudden death or ventricular tachyarrhythmias. These findings do not support routine correction of hypomagnesaemia.