Effect of Aliskiren on Post-Discharge Outcomes Among Diabetic and Non-Diabetic Patients Hospitalized for Heart Failure: Insights From the ASTRONAUT Trial

Study Questions:

What are differences in post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction receiving aliskiren, a direct renin inhibitor, with and without baseline diabetes mellitus?


This was a prespecified subgroup analysis of the ASTRONAUT (Aliskiren Trial on Acute Heart Failure Outcomes) trial. ASTRONAUT was a prospective, multicenter, international, randomized, double-blind, placebo-controlled trial investigating the role of oral aliskiren on outcomes among HHF patients. Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months. Data were also collected on change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months.


The subgroup analysis included 1,615 patients from the final ASTRONAUT efficacy analysis cohort (953 patients without diabetes mellitus and 662 patients with diabetes mellitus). The effect of aliskiren on cardiovascular death or HHF within 6 months did not significantly differ by baseline diabetes mellitus status (p = 0.08 for interaction), but reached statistical significance at 12 months (nondiabetes mellitus: hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.64-0.99; diabetes mellitus: HR, 1.16; 95% CI, 0.91-1.47; p = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline diabetes mellitus (nondiabetes mellitus: HR, 0.69; 95% CI, 0.50-0.94; diabetes mellitus: HR, 1.64; 95% CI, 1.15-2.33; p < 0.01 for interaction). Among nondiabetics, aliskiren was associated with a statistically significant greater decrease in NT-proBNP level compared with placebo at 1 and 6 months (p ≤ 0.02).


The authors concluded that addition of aliskiren to standard HHF therapy in nondiabetic therapy improves post-discharge outcomes at 12 months. These benefits are not seen in diabetic patients.


The limitations of a subgroup analysis aside, the present study indicates the impact of diabetes mellitus on the clinical effects of aliskiren in patients with reduced ejection fraction hospitalized for HF. These results provide convincing evidence to avoid direct renin inhibition in HHF patients with comorbid diabetes mellitus, but provide optimism about the potential benefits of aliskiren in nondiabetic patients with heart failure with reduced ejection fraction. As the authors have suggested, future prospective investigations should further clarify the potential benefits of renin inhibition in a larger cohort of HHF patients without diabetes mellitus.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Novel Agents, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Fumarates, Renin, Heart Failure, Diabetes Mellitus, Drosophila Proteins, Natriuretic Peptide, Brain

< Back to Listings