Usefulness of matrix metalloproteinase-9 plasma levels to identify patients with preserved left ventricular systolic function after acute myocardial infarction who could benefit from eplerenone

Am J Cardiol. 2012 Oct 15;110(8):1085-91. doi: 10.1016/j.amjcard.2012.05.049. Epub 2012 Jun 27.

Abstract

We sought to assess possible interactions between eplerenone use and a plasma marker of collagen turnover on prognosis in patients after acute myocardial infarction (AMI) and preserved left ventricular (LV) ejection fraction (≥40%). Three hundred three patients with AMI (58 ± 11 years old, 249 men) and preserved systolic LV function were studied prospectively for 24 months. Plasma levels of matrix metalloproteinase-9 (MMP-9) were assessed on day 7 after AMI. Patients were categorized according to whether (n = 201) or not (n = 102) they received eplerenone (25 mg/day) and their baseline MMP-9 levels using the cut-off level suggested by receiver operating characteristics analysis (12.7 ng/ml). Death from cardiovascular causes, nonfatal reinfarction, hospitalization for unstable angina, and development of heart failure symptoms were considered study end points. Eplerenone use was not associated with better prognosis in the entire study group (p = 0.132). However, a significant beneficial eplerenone effect on outcome was observed in patients with low baseline levels of MMP-9 (event-free survival for eplerenone vs noneplerenone arm 65% vs 35%, p = 0.005). Eplerenone had no effect (p = 0.741) in the subgroup of patients with high baseline MMP-9 levels. In conclusion, in patients after AMI with preserved LV systolic function, low baseline levels of MMP-9 identify a subgroup of patients in whom eplerenone use is associated with a survival benefit.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay
  • Eplerenone
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Myocardial Infarction / blood*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • ROC Curve
  • Spironolactone / analogs & derivatives*
  • Spironolactone / therapeutic use
  • Statistics, Nonparametric
  • Systole
  • Ventricular Function, Left / drug effects*

Substances

  • Biomarkers
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone
  • Matrix Metalloproteinase 9