ASTRONAUT Study: No Significant Post-Discharge Mortality Benefit Seen with Aliskiren

SAN FRANCISCO, CA—The results of the ASTRONAUT study revealed that aliskiren did not improve post-discharge mortality and/or hospitalizations when added to standard therapy in recently hospitalized patients with worsening chronic heart failure and reduced ejection fraction, stated Mihai Gheorghiade, MD, from the Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL.

Rates for post-discharge mortality and re-hospitalization are high in patients hospitalized for heart failure. Aliskiren, a direct renin inhibitor, has a distinct mechanism for RAAS blockade by inhibiting RAAS upstream at the point of pathway activation.

Dr. Gheorghiade and ASTRONAUT (Aliskiren Trial On Acute Heart Failure Outcomes) investigators tested whether aliskiren, in addition to standard therapy, delayed the time to first occurrence of either cardiovascular (CV) death or heart failure (HF) re-hospitalization in patients hospitalized for HF.

The ASTRONAUT Study is the first international, randomized, double-blind, placebo-controlled trial that enrolled hemodynamically stable hospitalized for heart failure (HHF) patients at a median of 5 days after admission to receive aliskiren 150mg (increased to 300mg as tolerated) daily or placebo continuously post-discharge, in addition to standard therapy. Eligible patients were >18 years with ejection fraction (EF) ≤40% and elevated natriuretic peptides (BNP ≥400pg/mL or NT-proBNP ≥1,600pg/mL); mean follow up was 11.3 months.

The primary composite end point was first occurrence of cardiovascular death or HF re-hospitalization within 6 months. This same end point was evaluated within 12 months. Secondary endpoints evaluated the first CV event within 12 months, all-cause mortality within 6 and 12 months, and change from baseline in NT-proBNP at 1, 6, and 12 months of follow-up.

In total, 1,639 patients were randomized to aliskiren (n=821) or placebo (n=818). At admission and randomization, median NT-proBNP was 4,239pg/mL and 2,718pg/mL, respectively. Overall, 41% of patients had diabetes mellitus. At randomization, patients were receiving diuretics (95.9%), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (84.2%), beta-blockers (82.5%), and mineralocorticoid receptor antagonists (57%).

Within six months, CV death occurred in 9.5% of the aliskiren (n=77) and 10.5% of the placebo (n=85) group (HR 95% CI 0.92 [0.68–1.26], P=0.60). HF re-hospitalization within six months occurred in 18.9% (n=153) and 20.6% (n=166) of the aliskiren and placebo group (HR 95% CI 0.90[0.72–1.12], P=0.35) respectively.

Dr. Gheorghiade added, “Further investigations are needed to evaluate effects of direct renin inhibitors with standard therapy in patients without diabetes who have been recently hospitalized for HF.”