Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: The Randomized Double-Blind Reminder Study

Montalescot, Gilles; Pitt, Bertram; De, E Lopez; Hamm, Christian W.; Flather, Marcus; Verheugt, Freek W.A.; Shi, Harry; Turgonyi, Eva; Orri, Miguel; Vincent, John; Zannad, Faı̈ez; Noll, Georg; Weir, Robin A.P.; O’Neill, Brian; Böhm, Michael; Hillis, W. S.; Grieve, Andrew; Rouleau, J L; Gerasimos, F.; Fitchett, David; Lepage, Serge; Madan, Mina; Sussex, Bruce; Tremblay, Guy; Welsh, Robert C.; Wong, G; Hutyra, Martin; Kettner, Jiří; Ošťádal, Petr; Špinar, Jindřich; Vojáček, Jan; Barboteu, M; Collet, Jean‐Philippe; Coste, Pierre; Cottin, Yves; Ducos, D.; Galinier, Michel; Teiger, Emmanuel; Zemour, Gilles; Bauersachs, Johann; Hambrecht, Rainer; Hauf, Gerhard F.; Heuer, H.; Mudra, Harald; Münzel, Thomas; Steiner, Stephan; Strasser, R. H.; Sydow, Karsten; Tschöpe, Carsten; Wachter, Rolf; Werner, Nicolas; Alexopoulos, D.; Babalis, Dimitris; Pyrgakis, Vlasios; Dézsi, Csaba András; Lupkovics, Géza; Polgár, Péter; Tomcsányi, János; Herrman, Jean-Paul; Berg, J. M. ten; Górny, Jerzy; Kubica, Julia Maria; Lewczuk, Jerzy; Żmuda, Witold; Hranai, M.; Kovář, František; Margoczy, Roman; Micko, Karol; Sumbal, J; Genover, Xavier Bosch; Ortiz, Antonio Fernández; Sala, M. Fiol; García, Cosme García; Muñoz, Carla; Blas, Juan Ramón Rey; Soriano, Francisco Ridocci; Adamson, Dawn; Alamgir, Farqad; Chauhan, Ashok; Lip, Gregory Y. H.; Martin, Trejeeve; McCann, Gerry P; Newby, David; Smith, David C.

doi:10.1093/eurheartj/ehu164

Cited by 131 publications

(95 citation statements)

References 25 publications

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“…23 In patients with acute ST-segment-elevation MI without HF, the early administration of eplerenone within 24 hours post MI allows reducing the rate of rehospitalization. 24 An early improvement of the coronary function/reserve may participate to such benefit. Of note, in patients with diabetes mellitus without clinical cardiovascular disease, receiving an angiotensin-converting enzyme inhibitor and a calcium channel antagonist, adenosine-stimulated coronary reserve is higher after 6 weeks of treatment with eplerenone in comparison with a thiazidic diuretic.…”

Section: Discussionmentioning

confidence: 99%

Vascular Smooth Muscle Mineralocorticoid Receptor Contributes to Coronary and Left Ventricular Dysfunction After Myocardial Infarction

et al. 2016

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C hronic heart failure (HF) after myocardial infarction (MI) is steadily increasing worldwide and remains a major cause of death. Mineralocorticoid receptor (MR) antagonists (MRAs) improve survival in patients with HF as illustrated by spironolactone in the RALES (Randomized Aldactone Evaluation Study) 1 trial and by eplerenone in the EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial, 2 which only included patients with post-MI. Recently, the EMPHASIS (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) study even showed that eplerenone is effective in slowing down the progression of mild-to-moderate HF. 3 However, MRAs are associated with side effects, such as hyperkalemia or gynecomastia; the latter is caused by the antiandrogenic properties of their steroidal structure. These adverse effects are responsible for the underuse of MRAs. 4 Understanding of the cell-specific contribution of MR to HF and of the effects of MRA on various cell subtypes will be useful for the future development of tissue-selective MR targeting approaches that would improve the benefit/risk ratio. 5A crucial role of cardiomyocyte MR has been demonstrated in mice with cardiomyocyte-specific MR deletion, which allows improving left ventricular (LV) function after either MI 6 or pressure overload induced by transverse aortic constriction. 7 The deletion of MR specifically in fibroblasts does not affect cardiac failure after aortic constriction. 7 The role of vascular MR has been underlined recently: the MR expressed in vascular smooth muscle cells (VSMCs) is involved in age-related Abstract-Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In this study, the role of MR expressed in vascular smooth muscle cells (VSMCs) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MR SMKO ) and mice treated with the MR antagonist finerenone (MI-fine) had improved left ventricular compliance and elastance when compared with infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary reserve assessed by magnetic resonance imaging was preserved (difference in myocardial perfusion before and after induction of vasodilatation, mL mg . The endothelial function, tested on isolated septal coronary arteries by analyzing the acetylcholine-induced nitric oxide-dependent relaxation, was also improved by MR deletion in VSMCs or by finerenone treatment (relaxation %: MI-CTL: 36±5, MI-MR SMKO : 54±3, and MI-fine: 76±4; P<0.05). Such impairment of the coronary endothelial function on MI involved an oxidative stress that was reduced when MR was deleted in VSMCs or by finerenone treatment. Moreover, short-term incubation of coronary arteries isolated from noninfarcted animals with low-dose angiotensin-II (10 −9 mol/L) induced oxidative stress and impaired...

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Section: Discussionmentioning

confidence: 99%

Vascular Smooth Muscle Mineralocorticoid Receptor Contributes to Coronary and Left Ventricular Dysfunction After Myocardial Infarction

et al. 2016

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“…Wdrożenie leczenia z zastosowaniem ACEI, LBA i MRA bezpośrednio po MI, zwłaszcza wtedy gdy towarzyszy mu dysfunkcja skurczowa LV, zmniejsza liczbę hospitalizacji z powodu HF i śmiertelność całkowitą [144][145][146][147][148]. Podobny efekt można uzyskać dzięki terapii statynami [137][138][139].…”

Section: Badania Genetyczne W Niewydolności Sercaunclassified

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Ponikowski

Voors

Anker³

et al. 2016

Kardiol Pol

385

406

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“…Clinical trials showed unambiguously that this benefit translates in patients with HF; the RALES, EPHESUS, and EMPHASIS trials demonstrated clear benefit of MR antagonists in HF, reducing morbidity and mortality, paving the way for broader clinical use of MRAs in cardiovascular (CV) diseases (Pitt et al, 1999(Pitt et al, , 2003Zannad et al, 2011). The benefit of MRAs now extend to early phases of myocardial infarction (MI) (REMINDER study) (Montalescot et al, 2014) and possibly to HF with preserved ejection fraction (post hoc study of the TOP-CAT trial) (Pfeffer et al, 2015).…”

Section: Mineralocorticoid Receptor and Cardiac Diseasesmentioning

confidence: 99%

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

2015

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Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: The Randomized Double-Blind Reminder Study

Abstract: NCT01176968.

Cited by 131 publications

References 25 publications

Vascular Smooth Muscle Mineralocorticoid Receptor Contributes to Coronary and Left Ventricular Dysfunction After Myocardial Infarction

Vascular Smooth Muscle Mineralocorticoid Receptor Contributes to Coronary and Left Ventricular Dysfunction After Myocardial Infarction

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

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