Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial.

Abstract

IMPORTANCE:

Hospitalizations for heart failure (HHF) represent a major health burden, with high rates of early postdischarge rehospitalization and mortality.

OBJECTIVE:

To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular (CV) death or HF rehospitalization among HHF patients.

DESIGN, SETTING, AND PARTICIPANTS:

International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission. Eligible patients were 18 years or older with left ventricular ejection fraction (LVEF) 40% or less, elevated natriuretic peptides (brain natriuretic peptide [BNP] ≥ 400 pg/mL or N -terminal pro-BNP [NT-proBNP] ≥ 1600 pg/mL), and signs and symptoms of fluid overload. Patients were recruited from 316 sites across North and South America, Europe, and Asia between May 2009 and December 2011. The follow-up period ended in July 2012.

INTERVENTION:

All patients received 150 mg (increased to 300 mg as tolerated) of aliskiren or placebo daily, in addition to standard therapy. The study drug was continued after discharge for a median 11.3 months. MAIN OUTCOME MEASURES Cardiovascular death or HF rehospitalization at 6 months and 12 months.

RESULTS:

In total, 1639 patients were randomized, with 1615 patients included in the final efficacy analysis cohort (808 aliskiren, 807 placebo). Mean age was 65 years; mean LVEF, 28%; 41% of patients had diabetes mellitus, mean estimated glomerular filtration rate, 67 mL/min/1.73 m2. At admission and randomization, median NT-proBNP levels were 4239 pg/mL and 2718 pg/mL, respectively. At randomization, patients were receiving diuretics (95.9%), β-blockers (82.5%), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (84.2%), and mineralocorticoid receptor antagonists (57.0%). In total, 24.9% of patients receiving aliskiren (77 CV deaths, 153 HF rehospitalizations) and 26.5% of patients receiving placebo (85 CV deaths, 166 HF rehospitalizations) experienced the primary end point at 6 months (hazard ratio [HR], 0.92; 95% CI, 0.76-1.12; P = .41). At 12 months, the event rates were 35.0% for the aliskiren group (126 CV deaths, 212 HF rehospitalizations) and 37.3% for the placebo group (137 CV deaths, 224 HF rehospitalizations; HR, 0.93; 95% CI, 0.79-1.09; P = .36). The rates of hyperkalemia, hypotension, and renal impairment/renal failure were higher in the aliskiren group compared with placebo.

CONCLUSION AND RELEVANCE:

Among patients hospitalized for HF with reduced LVEF, initiation of aliskiren in addition to standard therapy did not reduce CV death or HF rehospitalization at 6 months or 12 months after discharge.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00894387.

• Authors: Mihai Gheorghiade, Michael Böhm, Stephen J Greene, Gregg C Fonarow, Eldrin F Lewis, Faiez Zannad, Scott D Solomon, Fabio Baschiera, Jaco Botha, Tsushung A Hua, Claudio R Gimpelewicz, Xavier Jaumont, Anastasia Lesogor, Aldo P Maggioni, ASTRONAUT Investigators and Coordinators
• Journal: JAMA (JAMA) Vol. 309 Issue 11 Pg. 1125-35 (Mar 20 2013) ISSN: 1538-3598 [Electronic] United States
• PMID: 23478743 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Antihypertensive Agents
• Fumarates
• aliskiren
• Renin

Topics

• Aged
• Amides (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Double-Blind Method
• Female
• Follow-Up Studies
• Fumarates (therapeutic use)
• Heart Failure (drug therapy, mortality)
• Hospitalization (statistics & numerical data)
• Humans
• Male
• Middle Aged
• Patient Readmission
• Renin (antagonists & inhibitors)
• Stroke Volume
• Treatment Outcome
• Ventricular Dysfunction, Left