Aliskiren Trial on Acute Heart Failure Outcomes - ASTRONAUT

Mar 11, 2013
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Novartis Pharma AG
Date Presented:
01/01/2013
Date Published:
01/01/2013
Date Updated:
03/11/2013
Original Posted Date:
03/11/2013
References

Description:

The goal of the trial was to evaluate treatment with the direct renin inhibitor aliskiren compared with placebo among stabilized patients after hospitalization for heart failure.

Hypothesis:

Aliskiren will improve clinical outcomes.

Study Design

  • Placebo Controlled
  • Randomized
  • Parallel

Patient Populations:

  • Patients with chronic heart failure after a period of acute decompensation
  • Left ventricular ejection fraction ≤40%
  • BNP ≥400 pg/ml or NT-proBNP ≥1600 pg/ml
  • Hemodynamically and clinically stable

    Number of screened applicants: 2,134
    Number of enrollees: 1,639
    Duration of follow-up: median 11.3 months
    Mean patient age: 65 years
    Percentage female: 23%
    Ejection fraction: 28%

Exclusions:

  • Cardiac surgery, myocardial infarction, or stroke within the last 3 months
  • Estimated glomerular filtration rate <40 ml/min/1.73 m2
  • Potassium >5.0 mEq/L
  • Sodium <130 mEq/L

Primary Endpoints:

  • Cardiovascular mortality, or heart failure hospitalization at 6 months

Secondary Endpoints:

  • Cardiovascular mortality, or heart failure hospitalization at 12 months
  • Cardiovascular mortality, heart failure hospitalization, nonfatal myocardial infarction, nonfatal stroke, or sudden death at 12 months
  • All-cause mortality at 6 and 12 months
  • Change in NT-proBNP

Drug/Procedures Used:

Stabilized patients after hospitalization for heart failure were randomized to aliskiren 300 mg daily (n = 821) versus placebo (n = 818). Aliskiren was initiated at 150 mg daily. During the maintenance period, aliskiren could be down-titrated if needed.

Concomitant Medications:

  • Background medical therapy:
    - Diuretics: 96%
    - Angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker: 84%
    - Beta-blocker: 83%
    - Mineralocorticoid receptor antagonist: 57%
    - Digoxin: 39%
    - Antiplatelet therapy: 65%

Principal Findings:

Overall, 1,639 patients were randomized. The mean age was 65 years, 23% were women, 41% had diabetes, 21% had renal insufficiency, 64% had ischemic heart failure etiology, mean left ventricular ejection fraction was 28%, and mean N-terminal pro-B-type natriuretic peptide (NT-proBNP) at randomization was 2718 pg/ml.

The primary outcome of cardiovascular death or hospitalization for heart failure at 6 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 for diabetes status, where aliskiren appeared to be associated with a greater magnitude of benefit among nondiabetics.

- Cardiovascular death: 9.5% vs. 10.5% (p = 0.60), respectively
- Hospitalization for heart failure: 18.9% vs. 20.6% (p = 0.35), respectively

- Cardiovascular death or hospitalization for heart failure at 12 months: 35.0% vs. 37.3% (p = 0.36), respectively
- Cardiovascular death: 15.6% vs. 17.0% (p = 0.60), respectively
- Hospitalization for heart failure: 26.2% vs. 27.8% (p = 0.44), respectively

Aliskiren was associated with a significant reduction in NT-proBNP from baseline to follow-up vs. placebo (p < 0.01).

- Hyperkalemia: 20.9% vs. 17.5% (p = 0.09), respectively
- Renal failure: 16.6% vs. 12.1% (p = 0.01), respectively
- Hypotension: 17.1% vs. 12.6% (p = 0.01), respectively

Interpretation:

Among stabilized patients hospitalized for heart failure, the addition of aliskiren to standard medical therapy did not improve outcomes. Aliskiren was associated with a higher frequency of hyperkalemia, renal failure, and hypotension. The possible benefit of aliskiren among diabetics warrants further study.

References:

Gheorghiade M, Böhm M, Greene SJ, et al., on behalf of the ASTRONAUT Investigators and Coordinators. Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure: The ASTRONAUT Randomized Trial. JAMA 2013;309:1125-35.

Presented by Dr. Mihai Gheorghiade at ACC.13, San Francisco, March 11, 2013.

Keywords: Follow-Up Studies, Renin, Hypotension, Hyperkalemia, Renal Insufficiency, Fumarates, Heart Failure, Peptide Fragments, Stroke Volume, Hospitalization, Diabetes Mellitus, Natriuretic Peptide, Brain


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