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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

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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.

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Acknowledgements

The authors acknowledge Pfizer, Inc for editorial support.

Author information

Authors and Affiliations

  1. INSERM, Centre d’Investigations Cliniques Plurithématique 1433, F-CRIN INI-CRCT, INSERM U1116, Université de Lorraine, CHRU de Nancy, Nancy, France

    João Pedro Ferreira, Kévin Duarte, Patrick Rossignol & Faiez Zannad

  2. Cardiovascular Research and Development Unit, Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal

    João Pedro Ferreira

  3. Institut de Cardiologie, Centre Hospitalier Pitié-Salpêtrière (AP-HP, ACTION Group, University Paris 6), 47 boulevard de l’Hôpital, 75013, Paris, France

    Gilles Montalescot

  4. Division of Cardiology, University of Michigan School of Medicine, Ann Arbor, USA

    Bertram Pitt

  5. Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain

    Esteban Lopez de Sa

  6. Kerckhoff-Klinik, Heart Clinic, Bad Nauheim, Germany

    Christian W. Hamm

  7. Norwich Medical School, University of East Anglia, Norwich, UK

    Marcus Flather

  8. Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands

    Freek Verheugt

  9. Pfizer Inc., New York, USA

    Harry Shi & John Vincent

  10. Pfizer Ltd, Tadworth, Surrey, KT20 7NS, UK

    Eva Turgonyi & Miguel Orri

Authors
  1. João Pedro Ferreira
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  2. Kévin Duarte
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  3. Gilles Montalescot
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  4. Bertram Pitt
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  5. Esteban Lopez de Sa
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  6. Christian W. Hamm
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  7. Marcus Flather
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  8. Freek Verheugt
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  9. Harry Shi
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  10. Eva Turgonyi
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  11. Miguel Orri
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  12. Patrick Rossignol
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  13. John Vincent
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  14. Faiez Zannad
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Corresponding author

Correspondence to Faiez Zannad.

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Source of funding

The REMINDER study was funded by Pfizer, Inc.

Conflict of interest

JPF has no relevant conflicts of interest to report regarding the present manuscript. G.M., F.Z., L.d.S., C.W.H., M.F., F.V., and B.P. report to have received consulting or lecture fees from a number of pharmaceutical companies including Pfizer. J.V., E.T., M.O., and H.S. are full-time employees of Pfizer and own stock in this company. The complete author group had full access to all of the data in this study and take complete responsibility for the integrity of the data and the accuracy of the data analysis.

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Ferreira, J.P., Duarte, K., Montalescot, G. et al. 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 107, 49–59 (2018). https://doi.org/10.1007/s00392-017-1157-3

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  • DOI: https://doi.org/10.1007/s00392-017-1157-3

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