Format

Send to

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

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.

Author information

1
INSERM, Centre d'Investigations Cliniques Plurithématique 1433, F-CRIN INI-CRCT, INSERM U1116, Université de Lorraine, CHRU de Nancy, Nancy, France.
2
Cardiovascular Research and Development Unit, Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
3
Institut de Cardiologie, Centre Hospitalier Pitié-Salpêtrière (AP-HP, ACTION Group, University Paris 6), 47 boulevard de l'Hôpital, 75013, Paris, France.
4
Division of Cardiology, University of Michigan School of Medicine, Ann Arbor, USA.
5
Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain.
6
Kerckhoff-Klinik, Heart Clinic, Bad Nauheim, Germany.
7
Norwich Medical School, University of East Anglia, Norwich, UK.
8
Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands.
9
Pfizer Inc., New York, USA.
10
Pfizer Ltd, Tadworth, Surrey, KT20 7NS, UK.
11
INSERM, Centre d'Investigations Cliniques Plurithématique 1433, F-CRIN INI-CRCT, INSERM U1116, Université de Lorraine, CHRU de Nancy, Nancy, France. f.zannad@chru-nancy.fr.

Abstract

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

PMID:
28852839
DOI:
10.1007/s00392-017-1157-3
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center