Rationale and design of the multicentre, randomized, double-blind, placebo-controlled Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT)

• Published in: European journal of heart failure 2011-01, Vol.13 (1), p.100-106
• Main Authors: Gheorghiade, Mihai, Albaghdadi, Mazen, Zannad, Faiez, Fonarow, Gregg C., Böhm, Michael, Gimpelewicz, Claudio, Botha, Jaco, Moores, Shelley, Lewis, Eldrin F., Rattunde, Henning, Maggioni, Aldo
• Format: Article
• Language: English
• Subjects: Acute heart failure syndromes; Aliskiren; Amides - therapeutic use; Antihypertensive Agents - therapeutic use; Direct renin inhibition; Double-Blind Method; Europe; Fumarates - therapeutic use; Glomerular Filtration Rate - drug effects; Heart Failure - drug therapy; Heart Failure - mortality; Hemodynamics - drug effects; Hospitalization - statistics & numerical data; Humans; Multivariate Analysis; Outpatients - statistics & numerical data; Placebos; Proportional Hazards Models; Renin - antagonists & inhibitors; Renin-Angiotensin System - drug effects; Renin-angiotensin-aldosterone system; Research Design; Stroke Volume - drug effects; Syndrome; Time Factors; United States; Ventricular Function, Left - drug effects
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1093/eurjhf/hfq209

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 m2. 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. Perspective 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.