Rationale and design of the multicentre, randomized, double-blind, placebo-controlled Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT).
BACKGROUND
Hospitalizations for acute heart failure syndromes (AHFS) are associated with high post-discharge mortality and readmission rates in spite of available therapies. Renin-angiotensin-aldosterone system (RAAS) antagonists improve outcomes in outpatients with heart failure (HF) and reduced ejection fraction, however these therapies have not been tested in AHFS. Aliskiren is a direct renin inhibitor (DRI) that is known to enhance RAAS inhibition, which may result in improved clinical outcomes in AHFS. The aim of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) study is to evaluate the effect of aliskiren on cardiovascular death and HF in AHFS patients.


METHODS
ASTRONAUT will be an event-driven trial with an estimated enrolment of 1782 patients hospitalized with worsening chronic HF, a left ventricular ejection fraction ≤40%, and an estimated glomerular filtration rate ≥40 mL/min/1.73 m(2). Patients will be randomized 1:1 in a double-blind fashion to receive aliskiren or placebo, in addition to standard HF therapy. The primary endpoint will be a composite of time to either cardiovascular death or first occurrence of HF re-hospitalization.


CONCLUSIONS
Aliskiren is a DRI with a favourable neurohormonal and haemodynamic profile that may benefit patients hospitalized with worsening HF. Given the neurohormonal abnormalities that are present during and after hospitalization for AHFS, it is hypothesized that adding aliskiren to standard therapy will reduce post-discharge mortality and re-hospitalization. NCT00894387.
Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 1006, Chicago, IL 60611, USA. m-gheorghiade@northwestern.edu
Mihai
M
Gheorghiade
Mazen
M
Albaghdadi
Faiez
F
Zannad
Gregg C
GC
Fonarow
Michael
M
Böhm
Claudio
C
Gimpelewicz
Jaco
J
Botha
Shelley
S
Moores
Eldrin F
EF
Lewis
Henning
H
Rattunde
Aldo
A
Maggioni
D000577:Amides / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005060:Europe; D005650:Fumarates / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006439:Hemodynamics / Q000187:drug effects; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015999:Multivariate Analysis; D010045:Outpatients / Q000706:statistics & numerical data; D010919:Placebos; D016016:Proportional Hazards Models; D012084:Renin-Angiotensin System / Q000187:drug effects; D012107:Research Design; D013318:Stroke Volume / Q000187:drug effects; D013577:Syndrome; D013997:Time Factors; D014481:United States; D016277:Ventricular Function, Left / Q000187:drug effects; D000092502:Renin Inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D010919:Placebos; D000092502:Renin Inhibitors; C446481:aliskiren