João Pedro Ferreira1,2, Kévin Duarte1, Gilles Montalescot3, Bertram Pitt4, Esteban Lopez de Sa5, Christian W Hamm6, Marcus Flather7, Freek Verheugt8, Harry Shi9, Eva Turgonyi10, Miguel Orri10, Patrick Rossignol1, John Vincent9, Faiez Zannad11. 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.
RCT Entities:
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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