Early Aldosterone Blockade in Acute Myocardial Infarction: The ALBATROSS Randomized Clinical Trial.
BACKGROUND
Mineralocorticoid receptor antagonists (MRA) improve outcome in the setting of post-myocardial infarction (MI) heart failure (HF).


OBJECTIVE
The study sought to assess the benefit of an early MRA regimen in acute MI irrespective of the presence of HF or left ventricular (LV) dysfunction.


METHODS
We randomized 1,603 patients to receive an MRA regimen with a single intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) for 6 months in addition to standard therapy or standard therapy alone. The primary outcome of the study was the composite of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF at 6-month follow-up. Key secondary/safety outcomes included death and other individual components of the primary outcome and rates of hyperkalemia at 6 months.


RESULTS
The primary outcome occurred in 95 (11.8%) and 98 (12.2%) patients in the treatment and control groups, respectively (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.73 to 1.28). Death occurred in 11 (1.4%) and 17 (2.1%) patients in the treatment and control groups, respectively (HR: 0.65; 95% CI: 0.30 to 1.38). In a non-pre-specified exploratory analysis, the odds of death were reduced in the treatment group (3 [0.5%] vs. 15 [2.4%]; HR: 0.20; 95% CI: 0.06 to 0.70) in the subgroup of ST-segment elevation MI (n = 1,229), but not in non-ST-segment elevation MI (p for interaction = 0.01). Hyperkalemia >5.5 mmol/l(-1) occurred in 3% and 0.2% of patients in the treatment and standard therapy groups, respectively (p < 0.0001).


CONCLUSIONS
The study failed to show the benefit of early MRA use in addition to standard therapy in patients admitted for MI. (Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up; NCT01059136).
ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Caen, Caen, France.
Farzin
F
Beygui
ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Nimes, Nîmes, France.
Guillaume
G
Cayla
ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Caen, Caen, France.
Vincent
V
Roule
Service de Cardiologie, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
François
F
Roubille
Service de Cardiologie, Centre Hospitalier de Pau, Pau, France.
Nicolas
N
Delarche
ACTION Study Group, Institut de Cardiologie (AP-HP), Centre Hospitalier Universitaire Pitié-Salpêtriėre, Paris, France.
Johanne
J
Silvain
Service de Cardiologie, Centre Hospitalier Universitaire de Lille, Lille, France.
Eric
E
Van Belle
Service de Cardiologie, Centre Hospitalier d'Annecy, Annecy, France.
Loic
L
Belle
Service de Cardiologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Michel
M
Galinier
Service de Cardiologie, Centre Hospitalier Universitaire de Clermont Ferrand, Clermont Ferrand, France.
Pascal
P
Motreff
ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Nimes, Nîmes, France.
Luc
L
Cornillet
ACTION Study Group, Institut de Cardiologie (AP-HP), Centre Hospitalier Universitaire Pitié-Salpêtriėre, Paris, France.
Jean-Philippe
JP
Collet
Service de Cardiologie, Centre Hospitalier Universitaire d'Angers, Angers, France.
Alain
A
Furber
Service d'Accueil des Urgences et SAMU, Centre Hospitalier Universitaire de Lille, Lille, France.
Patrick
P
Goldstein
ACTION Study Group, SAMU, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France.
Patrick
P
Ecollan
ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Caen, Caen, France.
Damien
D
Legallois
ACTION Study Group, Service de Cardiologie, Centre Hospitalier Universitaire de Caen, Caen, France.
Alain
A
Lebon
ACTION Study Group, Unite de Recherche Clinique, Hôpital Lariboisière, Paris, France.
Hélène
H
Rousseau
Service de Cardiologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France.
Jacques
J
Machecourt
INSERM, CIC 1433 et Pôle de Cardiologie, Centre Hospitalier Universitaire de Nancy, Nancy, France.
Faiez
F
Zannad
ACTION Study Group, Unite de Recherche Clinique, Hôpital Lariboisière, Paris, France.
Eric
E
Vicaut
ACTION Study Group, Institut de Cardiologie (AP-HP), Centre Hospitalier Universitaire Pitié-Salpêtriėre, Paris, France. Electronic address: gilles.montalescot@aphp.fr.
Gilles
G
Montalescot
D000367:Age Factors; D000368:Aged; D002191:Canrenoic Acid / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D016037:Single-Blind Method; D013148:Spironolactone / Q000008:administration & dosage*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D002191:Canrenoic Acid
left ventricular dysfunction; mineralocorticoid receptor antagonists; mortality