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


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.


CONCLUSIONS
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.


BACKGROUND
NCT01176968.
Institut de Cardiologie, Centre Hospitalier Pitié-Salpêtrière (AP-HP, ACTION Group, University Paris 6), 47 boulevard de l'Hôpital, 75013 Paris, France gilles.montalescot@psl.aphp.fr.
Gilles
G
Montalescot
Division of Cardiology, University of Michigan School of Medicine, Ann Arbor, USA.
Bertram
B
Pitt
Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain.
Esteban
E
Lopez de Sa
Kerckhoff-Klinik, Heart Clinic, Bad Nauheim, Germany.
Christian W
CW
Hamm
Norwich Medical School, University of East Anglia, Norwich, UK.
Marcus
M
Flather
Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands.
Freek
F
Verheugt
Pfizer Inc., New York, USA.
Harry
H
Shi
Pfizer Ltd, Tadworth, Surrey KT 20 7NS, UK.
Eva
E
Turgonyi
Pfizer Ltd, Tadworth, Surrey KT 20 7NS, UK.
Miguel
M
Orri
Pfizer Inc., New York, USA.
John
J
Vincent
Centre d'Investigation Clinique INSERM, Université de Lorraine and CHU, Nancy, France.
Faiez
F
Zannad
D004311:Double-Blind Method; D000077545:Eplerenone; D005260:Female; D006333:Heart Failure / Q000517:prevention & control; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000188:drug therapy*; D010359:Patient Readmission; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone
B-type natriuretic peptide; Eplerenone; Mineralocorticoid receptor antagonists; Myocardial infarction; Potassium