• Cardiology Clinical Trials
• Heart Failure

• Cardiology & Cardiovascular Medicine
• Cardiology Clinical Trials
• Heart Failure

Aliskiren in addition to standard therapy does not reduce cardiovascular (CV) death or heart failure (HF) rehospitalization in patients hospitalized for HF with reduced left ventricular ejection fraction (LVEF). Mihai Gheorghiade, MD, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA, presented data from the Six Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality in Patients With Acute Decompensated Heart Failure trial [ASTRONAUT; Gheorghiade M et al. JAMA 2013].

Despite the availability of several evidenced-based therapies for the treatment of patients hospitalized with HF, postdischarge mortality is as high as 14% and rehospitalization within 60 to 90 days is ∼30% [Gheorghiade M et al. JAMA 2006]. The ASTRONAUT trial tested the hypothesis that the direct renin inhibitor, aliskiren, may improve postdischarge outcomes for patients hospitalized with HF when initiated during hospitalization and continued post discharge [Gheorghiade M et al. Eur J Heart Fail 2011].

In the international Phase 3, double-blind, placebo-controlled ASTRONAUT trial, 1639 patients hospitalized with HF were randomized to receive either 150 mg (increased to 300 mg as tolerated) of aliskiren or placebo daily along with standard therapy [Gheorghiade M et al. JAMA 2013]. Patients were eligible if they had an LVEF ≤40%, B-type natriuretic peptide (BNP) ≥400 pg/mL or N-terminal pro-BNP ≥1600 pg/mL at admission, and a systolic blood pressure ≥110 mm Hg for at least 6 hours.

The study drug was continued for a median 11.3 months after discharge, and 1615 patients were included in the final efficacy analysis cohort. The primary endpoint was CV death or rehospitalization for HF within 6 months. CV death or rehospitalization for HF within 12 months was the key secondary endpoint.

No significant difference was observed between the aliskiren and placebo treatment groups for the primary endpoint of CV death or HF rehospitalization within 6 months (24.9% vs 26.5%; HR, 0.92; 95% CI, 0.76 to 1.12; p=0.41). In addition, no significant difference was observed for the key secondary endpoint of CV death or rehospitalization for HF within 12 months in the patients receiving aliskiren compared with those receiving placebo (35.0% vs 37.3%; HR, 93; 95% CI, 0.79 to 1.09; p=0.36).

There was a significant treatment interaction for all-cause mortality dependent upon the presence of diabetes. Specifically, patients with diabetes receiving aliskiren had a significantly higher rate of all-cause mortality (HR, 1.64; 95% CI, 1.15 to 2.33) within 12 months of randomization compared with patients without diabetes (HR, 0.69; 95% CI, 0.50 to 0.94; p for interaction <0.001). There was a similar treatment interaction for CV death or rehospitalization for HF within 12 months with diabetic patients receiving aliskiren experiencing a higher rate of CV death or HF rehospitalization (HR, 1.16; 95% CI, 0.91 to 1.47) compared with patients without diabetes (HR, 0.80; 95% CI, 0.64 to 0.99; p for interaction=0.03). Although this interaction was statistically significant suggesting heterogeneity in the impact of aliskiren versus placebo among diabetic and nondiabetic subjects for all-cause mortality and CV death/HF rehospitalization, this finding must be interpreted cautiously given the inherent statistical limitations.

The rates of hyperkalemia, renal impairment or renal failure, and hypotension were all more commonly observed in subjects receiving aliskiren versus placebo (Table 1).

Dr. Gheorghiade concluded that the data from the ASTRONAUT trial demonstrate that when added to contemporary medical therapy for patients with systolic dysfunction hospitalized for HF, there was no clinical benefit to the addition of aliskiren. The impact of aliskiren among different patient populations, particularly the tendency toward worse outcomes in patients with diabetes, who are hospitalized for HF warrants further study.

• Download figure
• Open in new tab
• Download powerpoint

The editors would like to thank the many members of the American College of Cardiology presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.

• © 2013 MD Conference Express®