Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure

insights from the ASTRONAUT trial

  • Maggioni, Aldo P.
  • Greene, Stephen J.
  • Fonarow, Gregg C.
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  • Visconti, Luigi Oltrona
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  • Cavallini, Claudio
  • Di Biase, Matteo
  • Masini, Dott Franco
  • Vassanelli, Corrado
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  • Borghi, Claudio
  • Volpe, Massimo
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  • Bueno, Manuel Gomez
  • Selles, Manuel Martinez
  • Cabrera, Jose Angel
  • Freire, Ramon Bover
  • Gonzalez Juanatey, Jose Ramon
  • Comin, Josep
  • Soriano, FranciscoRidocci
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  • Lama, Manuel Geraldia
  • Schaufelberger, Maria
  • Brunotte, Richard
  • Ullman, Bengt
  • Hagerman, Inger
  • Cizinsky, Stella
  • Cherng, Wen-Jin
  • Yu, Wen-Chung
  • Kuo, Chi-Tai
  • Chang, Kuan-Cheng
  • Lai, Wen-Ter
  • Kuo, Jen-Yuan
  • Ural, Dilek
  • Badak, Ozer
  • Akin, Mustafa
  • Yigit, Zerrin
  • Yokusoglu, Mehmet
  • Yilmaz, Mehmet
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  • Peberdy, Mary Ann
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  • Graham, Susan
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  • Chung, Eugene
  • Dunlap, Stephanie
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  • Katz, Richard
  • Murali, Srinivas
  • Izzo, Joseph L.
  • Callister, Tracy
  • Phillips, Roland
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  • Winterton, John
  • Meymandi, Sheba
  • Heilman, Karl III
  • Oren, Ron
  • Zolty, Ronald
  • Brottman, Michael
  • Gunawardena, D.R.
  • Adams, Kirkwood
  • Barnard, Denise
  • Klapholz, Marc
  • Fulmer, James

  • 1Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence, Italy

    2Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, 201 East Huron, Galter 3-150, Chicago, IL, USA

    3Ahmanson-UCLA Cardiomyopathy Center, University of California Los Angeles, Los Angeles, CA, USA

    4Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany

    5Clinical Investigation Center, INSERM-CHU de Nancy Hôpital Jeanne D'Arc, Dommartin-les Toul Cedex, France

    6Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA

    7Novartis Pharma AG, Basel, Switzerland

    8Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Corresponding author. Tel: +1 312 695 0051, Fax: +1 312 695 1434, Email: [email protected]

Received June 30, 2013

Accepted July 31, 2013

European Heart Journal 34(40):p 3117-3127, October 21, 2013. | DOI: 10.1093/eurheartj/eht342

Aims

The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM).

Methods and results

ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64–0.99; DM: HR: 1.16, 95% CI: 0.91–1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50–0.94; DM: HR: 1.64, 95% CI: 1.15–2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71–1.93; DM: HR: 2.39, 95% CI: 1.30–4.42; P = 0.07 for interaction).

Conclusion

This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.

Copyright © Copyright Oxford University Press 2013.
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