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

Gilles Montalescot (1) , Bertram Pitt (2) , Esteban Lopez de Sa (3) , Christian Hamm (4) , Marcus Flather (5) , Freek Verheugt (6) , Harry Shi (7) , Eva Turgonyi (8) , Miguel Orri (8) , John B. Vincent (7) , Faiez Zannad (9) , G. Noll , R. Weir , B. O'Neill , M. Bohm , W. Hillis , A. Grieve , J. Rouleau , F. Gerasimos , D. Fitchett , S. Lepage (10) , M. Madan , B. Sussex , G. Tremblay , R. Welsh , G. Wong , M. Hutyra , J. Kettner , P. Ostadal , J. Spinar , J. Vojacek , M. Barboteu (11) , J. Collet , P. Coste , Y. Cottin (12) , D. Ducos , M. Galinier (13) , E. Teiger , G. Zemour , J. Bauersachs , R. Hambrecht , G. Hauf , H. Heuer , H. Mudra , T. Munzel , S. Steiner , R. Strasser , K. Sydow , C. Tschope , R. Wachter , N. Werner , D. Alexopoulos , D. Babalis , V. Pyrgakis , C. Dezsi , G. Lupkovics , P. Polgar , J. Tomcsanyi , J. Herrman , J. ten Berg , J. Gorny (14) , J. Kubica , J. Lewczuk , W. Zmuda , M. Hranai , F. Kovar , R. Margoczy , K. Micko , J. Sumbal , X. Genover , A. Ortiz , F. Sala , G. Garcia (15) , C. Muñoz (16) , J. Rey Blas , F. Soriano , D. Adamson , F. Alamgir , A. Chauhan , G. Lip , T. Martin , G. Mccann , D. Newby , D. Smith

1 CHU Pitié-Salpêtrière [AP-HP]
2 University of Michigan [Ann Arbor]
3 Hospital Universitario La Paz
4 Kerckhoff-Klinik
5 Norwich Medical School
6 OLVG - Onze Lieve Vrouwe Gasthuis
7 Pfizer
8 Pfizer Ltd
9 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
10 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
11 LAMPS - LAboratoire de Modélisation Pluridisciplinaire et Simulations
12 CHU Dijon
13 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
14 LASIRE - Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516
15 CSVB - Conception, synthèse et vectorisation de biomolécules
16 FTUAM - Departamento de Fisica Teorica C-XI

AIMS: We aimed to assess the impact of eplerenone on cardiovascular (CV) outcomes in STEMI without known heart failure, when initiated within 24 h of symptom onset. METHODS AND RESULTS: In this randomized, placebo-controlled, double-blind trial, we assigned 1012 patients with acute STEMI and without a history of heart failure to receive either eplerenone (25-50 mg once daily) or placebo in addition to standard therapy. The primary endpoint was the composite of CV mortality, re-hospitalization, or, extended initial hospital stay, due to diagnosis of HF, sustained ventricular tachycardia or fibrillation, ejection fraction ≤40%, or elevated BNP/NT-proBNP at 1 month or more after randomization. BNP elevation was defined as BNP levels or values above 200 pg/mL or NT-proBNP values above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) or above 1800 pg/mL (patients older than 75). After a mean follow-up of 10.5 months, the primary endpoint occurred in 92 patients (18.2%) in the eplerenone group and in 149 patients (29.4%) in the placebo group [adjusted hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.45-0.76; P < 0.0001]. The primary endpoint was driven by a high BNP/NT-proBNP level (adjusted HR, 0.60; 95% CI, 0.45-0.79; P < 0.0003). Adverse event rates were similar in both groups. Serum potassium levels exceeded 5.5 mmol/L in 5.6 vs. 3.2% (P = 0.09) and were below 3.5 mmol/L in 1.4 vs. 5.6% of patients (P = 0.0002), in the eplerenone and placebo groups, respectively. CONCLUSION: The addition of eplerenone during the acute phase of STEMI was safe and well tolerated. It reduced the primary endpoint over a mean 13 months follow-up mostly because of significantly lower BNP/NT-proBNP levels. Additional studies are needed to clarify the role of early use of MRAs in STEMI patients without heart failure. CLINICAL TRIAL REGISTRATION: NCT01176968.

Mots clés: B-type natriuretic peptide; Eplerenone; Mineralocorticoid receptor antagonists; Myocardial infarction; Potassium

Domaines: Cardiologie et système cardiovasculaire

Gilles Montalescot, Bertram Pitt, Esteban Lopez de Sa, Christian Hamm, Marcus Flather, et al.. Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: The Randomized Double-Blind Reminder Study. European Heart Journal, 2014, 35 (34), pp.2295 - 2302. ⟨10.1093/eurheartj/ehu164⟩. ⟨hal-01738642⟩