Effect of eplerenone on extracellular cardiac matrix biomarkers in patients with acute ST-elevation myocardial infarction without heart failure: insights from the randomized double-blind REMINDER Study

Clin Res Cardiol. 2018 Jan;107(1):49-59. doi: 10.1007/s00392-017-1157-3. Epub 2017 Aug 29.


Objective: Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with an acute myocardial infarction (MI).

Methods: The REMINDER trial assessed the effect of eplerenone in patients with an acute ST-elevation Myocardial Infarction (STEMI) without known heart failure (HF), when initiated within 24 h of symptom onset. The primary outcome was almost totally (>90%) driven by natriuretic peptide (NP) thresholds after 1-month post-MI (it also included a composite of cardiovascular death or re-hospitalization or new onset HF or sustained ventricular tachycardia or fibrillation or LVEF ≤40% after 1-month post-MI). This secondary analysis aims to assess the extracellular matrix marker (ECMM) levels with regards to: (1) patients` characteristics; (2) determinants; (3) and eplerenone effect.

Results: Serum levels of ECMM were measured in 526 (52%) of the 1012 patients enrolled in the REMINDER trial. Patients with procollagen type III N-terminal propeptide (PIIINP) above the median were older and had worse renal function (p < 0.05). Worse renal function was associated with increased levels of PIIINP (standardized β ≈ 0.20, p < 0.05). Eplerenone reduced PIIINP when the levels of this biomarker were above the median of 3.9 ng/mL (0.13 ± 1.48 vs. -0.37 ± 1.56 ng/mL, p = 0.008). Higher levels of PIIINP were independently associated with higher proportion of NP above the prespecified thresholds (HR = 1.95, 95% CI 1.16-3.29, p = 0.012).

Conclusions: Eplerenone effectively reduces PIIINP levels when baseline values were above the median. Eplerenone may limit ECMM formation in post-MI without HF.

Keywords: Eplerenone; Extracellular cardiac markers; Myocardial infarction.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • Double-Blind Method
  • Eplerenone
  • Female
  • Humans
  • Linear Models
  • Logistic Models
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood*
  • Principal Component Analysis
  • Procollagen / blood*
  • Proportional Hazards Models
  • ST Elevation Myocardial Infarction / blood
  • ST Elevation Myocardial Infarction / diagnosis
  • ST Elevation Myocardial Infarction / drug therapy*
  • ST Elevation Myocardial Infarction / physiopathology
  • Spironolactone / adverse effects
  • Spironolactone / analogs & derivatives*
  • Spironolactone / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Troponin I / blood
  • Troponin T / blood


  • Biomarkers
  • Mineralocorticoid Receptor Antagonists
  • Peptide Fragments
  • Procollagen
  • Troponin I
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • procollagen Type III-N-terminal peptide
  • Natriuretic Peptide, Brain
  • Spironolactone
  • Eplerenone