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

Pedro Ferreira, João, Duarte, Kévin, Montalescot, Gilles, Pitt, Bertram, Lopez de Sa, Esteban, Hamm, Christian W, Flather, Marcus, Verheugt, Freek, Shi, Harry, Turgonyi, Eva, Orri, Miguel, Rossignol, Patrick, Vincent, John and Zannad, Faiez (2018) 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. Clinical Research in Cardiology, 107 (1). 49–59. ISSN 1861-0684

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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.

Item Type:	Article
Uncontrolled Keywords:	myocardial infarction,extracellular cardiac markers,eplerenone
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023)
Depositing User:	Pure Connector
Date Deposited:	13 Sep 2017 05:06
Last Modified:	22 Oct 2022 03:07
URI:	https://ueaeprints.uea.ac.uk/id/eprint/64819
DOI:	10.1007/s00392-017-1157-3

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