Prognostic relevance of magnesium alterations in patients with a myocardial infarction and left ventricular dysfunction: insights from the EPHESUS trial

Author:

Martens Pieter123ORCID,Ferreira João Pedro45,Vincent John6,Abreu Paula6,Busselen Martijn6,Mullens Wilfried12,Tang Wai Hong Wilson3,Böhm Michael7ORCID,Pitt Bertram8ORCID,Zannad Faiez45ORCID,Rossignol Patrick45

Affiliation:

1. Department of Cardiology, Ziekenhuis Oost Limburg, Genk, Belgium

2. Department of Medicine and Life Sciences, University Hasselt, Hasselt, Belgium

3. Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA

4. Université de Lorraine, Inserm, Centre d’Investigations Cliniques-1433, France

5. Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT, Nancy, France

6. Pfizer Inc, New York, NY, USA

7. Klinik für Innere Medizin III, Saarland University, Saarbrücken, Germany

8. University of Michigan, Ann Arbor, MI, USA

Abstract

Abstract Aims Magnesium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). The relation between serum magnesium and clinical outcomes is insufficiently elucidated in this population. Methods and results The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hypomagnesemia and hypermagnesemia were defined as a serum magnesium <0.66 and >1.10 mmol/L, respectively. Linear mixed models and time-dependent Cox regression analysis were used to determine the effect of eplerenone on magnesium changes and the prognostic importance of magnesium. The co-primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV hospitalization. A total of 5371 patients had a post-baseline magnesium measurement. At baseline, 231 (4.3%) patients had hypomagnesemia and 271 (5.0%) patients had hypermagnesemia. During a median follow-up of 16 months, 682 (13%) developed hypomagnesemia and 512 (9.5%) hypermagnesemia. Eplerenone treatment did not result in a different magnesium level during follow-up (P = 0.14). After covariate adjustment hypo- and hypermagnesemia were not associated with a higher risk of CV events. Magnesium levels did not modulate the effect of a high potassium (>5 mmol/L) or low potassium (<4 mmol/L) on the clinical outcome. Baseline magnesium levels did not influence the treatment effect of eplerenone (P-interaction > 0.1 for all primary and secondary endpoints). Conclusion In patients with MI complicated by LVSD or HF, magnesium alterations were not associated with clinical outcomes nor did they influence the effect of eplerenone. Serum magnesium did not modulate the effect of potassium changes on clinical outcome or the treatment effect of eplerenone. ClinicalTrials.gov identifier NCT00232180.

Funder

Pfizer

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine,Critical Care and Intensive Care Medicine,General Medicine

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