Aliskiren Provides No Benefit as Add-on Therapy for Patients Hospitalized with Heart Failure

Patients hospitalized with chronic heart failure do not experience improvements in post-discharge mortality or rehospitalization rates when the direct rennin inhibitor aliskiren is added to standard treatment.

Mihai Gheorghiade, MD, professor of medicine and surgery at Northwestern University, presented results of the late-breaking ASTRONAUT clinical trial at ACC.13, the 62nd Annual Scientific Session & Expo of the American College of Cardiology. The goal of the parallel trial was to evaluate treatment with the direct renin inhibitor aliskiren compared with placebo among stabilized patients after hospitalization for heart failure.

Post-discharge mortality and rehospitalization rates remain high in patients hospitalized for heart failure, even among those treated with evidence-based therapies. The ASTRONAUT trial assessed whether neurohormonal modulation with aliskiren in addition to standard therapy during the early post-discharge period improves long-term clinical outcomes.

Out of 2,134 screened applicants, 1,639 patients, stabilized after hospitalization for heart failure, were randomized to aliskiren 300 mg daily (821) versus placebo (818). Aliskiren was initiated at 150 mg daily, allowing for down-titration if necessary during maintenance period.

Participants were also treated with standard therapies, including diuretics (96%), angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (84%), beta-blocker (83%), mineralocorticoid receptor antagonist (57%), digoxin (39%), and antiplatelet therapy (65%).

Included were patients with chronic heart failure after a period of acute decompensation, left ventricular ejection fraction less than 40%, and who were hemodynamically and clinically stable. The average age of participants was about 65. Nearly one-quarter (23%) of participants were women, 41% had diabetes, 21% had renal insufficiency, 64% had ischemic heart failure etiology, and mean left ventricular ejection fraction was 28%.

Patients were excluded for cardiac surgery, myocardial infarction, or stroke within the last three months prior to the start of the study.

Primary endpoints were cardiovascular mortality, or heart failure hospitalization at six months. Secondary endpoints were cardiovascular mortality, heart failure hospitalization, nonfatal myocardial infarction (MI), nonfatal stroke, or sudden death at 12 months; and all-cause mortality at 6 and 12 months.

The primary outcome of cardiovascular death or hospitalization for heart failure at six months occurred in 24.9% of the aliskiren group versus 26.5% of the placebo group (P= 0.41). The outcomes were similar among various subgroups, except where aliskiren appeared associated with greater benefit among diabetics. Cardiovascular death at six months occurred in 9.5% versus 10.5% (P= 0.60), respectively. Hospitalization for heart failure occurred in 18.9% versus 20.6% (P= 0.35), respectively.

Cardiovascular death or hospitalization for heart failure at 12 months occurred in 35.0% of the aliskiren and 37.3% of the placebo groups (P= 0.36). Cardiovascular death occurred at 12 months in the aliskiren and placebo groups at 15.6% versus 17.0% (P= 0.60), respectively; and hospitalization for heart failure occurred at 26.2% versus 27.8% (P= 0.44), respectively.

The aliskiren group experienced more frequent hyperkalemia (20.9%) compared with the placebo group (17.5%), as well as more frequent renal failure (16.6% vs. 12.1%) and hypotension (17.1% vs. 12.6%).

Among stabilized patients hospitalized for heart failure, the addition of aliskiren to standard medical therapy did not improve outcomes, even in patients stabilized at discharge and maintaining renal function. Aliskiren was associated with greater occurrence of hyperkalemia, renal failure, and hypotension. The possible benefits of aliskiren treatment seen among diabetics warrants further study. There was no difference in treatment effect for primary endpoint. ASTRONAUT did not support routine administration of aliskiren to patients recently hospitalized for worsening chronic heart failure.