Multiple drug classes have been proven to decrease mortality or re-hospitalization in patients with heart failure (HF) due to a reduced left ventricular ejection fraction (HFrEF), including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRA).1 With the Center of Medicare and Medicaid Services (CMS) Readmissions Reduction program, reducing the readmissions for this patient population has become increasingly important to hospitals. Nevertheless, national averages still reflect 30-day readmission rates as high as 22.5% for Medicare beneficiaries with HF.2
The utility of the direct renin inhibitor, aliskiren in HFrEF remains unclear. The concept behind using a direct renin inhibitor arose as some of the drug classes (ACEIs, ARBs and MRAs) that encompass the current standard of therapy for HFrEF produce a compensatory increase in renin, which may offset some of the benefits of these drugs. Aliskiren is the first and only direct renin inhibitor on the market, and proved to lower natriuretic peptide levels and serum renin activity in individuals with chronic HF in the ALOFT trial.3 The Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) aimed to investigate if this translated into a reduction in hospitalizations and mortality.
The ASTRONAUT trial was a prospective, international, randomized, double-blind, placebo controlled study designed to assess the effect of aliskiren on HF readmissions and cardiovascular (CV) mortality at 6 and 12 months after a hospitalization for HF. Hemodynamically stable HF patients with a left ventricular ejection fraction of 40% or less, signs of fluid overload, and increased natriuretic peptides were included. In addition to receiving standard therapy, patients were randomized at a median of 5 days after admission to aliskiren 150 mg daily (increased to 300 mg as tolerated) or placebo daily. Standard therapy was at the discretion of the physician and could include diuretics, digoxin, ACEIs, ARBs, BBs, and MRAs. The primary and secondary endpoints of the trial were first occurrence of CV death or re-hospitalization at 6 and 12 months post randomization, respectively. Other secondary endpoints included first CV event within 12 months, all-cause mortality within 6 and 12 months, changes in baseline N-Terminal (NT) pro-BNP level at 1, 6 and 12 months, and quality of life (QOL).4
A total of 1615 patients were included with a mean age of 64.6 years, 77% males, and a mean LVEF of 27.9%. At 6 months, there was no difference in the primary endpoint with 24.9% of the aliskiren group and 26.5% of the placebo group experiencing either a CV death or re-hospitalization (p = 0.41). At 12 months, 35% of the aliskiren group and 37.3% in the placebo group experienced the secondary endpoint (p = 0.36). No significant difference in CV death or re-hospitalizations occurred. The only significant finding was a reduction in myocardial infarction in the aliskiren group (2.2% vs. 4.7% with placebo, HR 0.47, 95% CI, 0.27-0.83, p=0.009).4 In accordance with the ALOFT trial, NT pro-BNP levels ...