No Reduction in Mortality or Readmission with Addition of Aliskiren for HF Patients (ASTRONAUT)

Clinical question

Does the addition of aliskiren, a direct renin inhibitor, to standard therapy decrease mortality and readmission in patients hospitalized for worsening heart failure?

Bottom line

The addition of aliskiren to standard therapy in patients hospitalized with heart failure (HF) does not reduce cardiovascular mortality or HF readmission rates. LOE = 1b

Reference

Gheorghiade M, Böhm M, Greene SJ, et al, for the ASTRONAUT Investigators and Coordinators. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure. JAMA 2013;309(11):1125-1135.

Study design

Randomized controlled trial (double-blinded)

Funding source

Industry

Allocation

Uncertain

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Despite current standard therapy, postdischarge mortality and rehospitalizations remain high for patients hospitalized for HF. To study the effect of direct renin inhibitors on these outcomes, investigators enrolled adults hospitalized for worsening HF with a left ventricular ejection fraction (LVEF) of 40% or less. Once these patients were clinically and hemodynamically stable, they were randomized to receive aliskiren 150 mg daily or placebo. Study patients were followed up at regular intervals and the aliskiren dose was increased to 300 mg daily as long as the initial dose was tolerated. Aliskiren, either 150 mg or 300 mg, was then continued up to a maximum follow-up time of 12 months. All patients also received standard HF therapy at the discretion of their treating physicians. The 2 groups had similar baseline characteristics. The patients’ mean age was 65 years, mean LVEF was 28%, and the majority were New York Heart Association Class III-IV at randomization. For the primary end point of either cardiovascular death or HF rehospitalization at 6 months, there was no significant difference between the aliskiren and placebo groups. Events rates between the 2 groups were also similar at 12 months. The aliskiren group was more likely to experience hyperkalemia, hypotension, and renal impairment or renal failure. Additionally, a subgroup analysis showed that patients with diabetes fared worse with aliskiren, with a greater risk of all-cause mortality at 12 months, than those who took placebo.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.