Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure: The ASTRONAUT Randomized Trial

Study Questions:

Does the direct renin inhibitor aliskiren improve outcomes in patients hospitalized with heart failure (HF)?

Methods:

ASTRONAUT (Aliskiren Trial on Acute Heart Failure Outcomes) was a double-blind, randomized, multicenter trial of aliskiren (150 mg titrated to 300 mg daily) versus placebo administered to hemodynamically stable hospitalized patients with HF, a left ventricular ejection fraction (LVEF) ≤40%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1600 pg/ml. Patients received a median 11 months of therapy. The main outcomes of interest were cardiovascular (CV) death or HF hospitalization at 6 and 12 months.

Results:

Aliskiren was administered to 808 patients; 807 patients received placebo. Mean patient age was 65 years, mean LVEF was 28%, and mean NT-proBNP was 2718 pg/ml. At 6 months, 25% (77 CV deaths, 153 HF hospitalizations) of patients on aliskiren met the primary endpoint compared with 27% (85 CV deaths and 176 HF hospitalizations) on placebo (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.76-1.12). At 12 months, 35% and 37% of patients on aliskiren and placebo, respectively, met the endpoint (HR, 0.93; 95% CI, 0.79-1.1). Patients on aliskiren were more likely to have hypotension, hyperkalemia, and renal insufficiency. Further, all-cause death was higher in diabetic patients (HR, 1.64; 95% CI, 1.2-2.3 compared with nondiabetics).

Conclusions:

The authors concluded that aliskiren did not improve outcomes in patients with systolic HF.

Perspective:

Patients with decompensated HF have high renin-angiotensin (RAAS) and sympathetic nervous system activation that can be deleterious. In the ASTRONAUT study, enrolled patients experienced an HF decompensation despite being on acceptable evidence-based HF drug regimens. However, the ASTRONAUT study failed to demonstrate a significant benefit or strong trend toward improved outcomes following further renin inhibition. Further, diabetics tended to experience worse outcomes on aliskiren therapy. Like catecholamine-resistant cardiac shock, perhaps patients with very high renin levels on evidence-based medications do not gain benefit from more renin inhibition because renin levels merely reflect a state of chronic HF decompensation and physiologic resistance to RAAS hormones. Reducing readmissions for HF is going to be a challenge when new therapies to add to present evidence-based medications are lacking.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Fumarates, Heart Failure


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