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Effects of Candesartan on Left Ventricular Function, Aldosterone and BNP in Chronic Heart Failure

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Abstract

Purpose

Heart failure (HF) is characterized by activation of neurohormonal systems such as aldosterone and natriuretic peptides. In the absence of published data, CandHeart trial was designed to assess the effects on left ventricular (LV) function, aldosterone and brain natriuretic peptide (BNP) of candesartan in patients with HF and preserved (LVEF ≥ 40%) or depressed (LVEF <40%) LV systolic function.

Methods

A total of 514 patients with stable symptomatic NYHA II-IV HF and any left ventricular ejection fraction (LVEF)were randomized to candesartan (target dose 32 mg once daily) as add-on therapy or standard medical therapy alone. Standardized echocardiographic exams were performed locally under central quality control, whereas biomarkers were assayed in a core laboratory.

Results

The majority of patients (73.3%) were NYHA II and on ACE inhibitors (91.8%) and beta-blockers (85.4%). Mean age was 66 ± 11 years. Mean LVEF was 36.2 ± 9.7% and 24.9% of patients had LVEF ≥ 40%. LVEF increased significantly more in the candesartan group (p = 0.09 at 12 weeks and p = 0.01 at 48 weeks) and left ventricular end-diastolic diameter decreased in candesartan group (p = 0.05 at 12 weeks). Candesartan significantly reduced aldosterone at 48 weeks (p = 0.009). BNP was reduced similarly over time in both study groups (p = 0.35 and p = 0.98 at 12 and 48 weeks, respectively). There were 6.6% of discontinuations of candesartan for adverse events.

Conclusions

In CandHeart, the addition of candesartan to standard medical treatment did not reduce circulating BNP more than standard therapy (primary endpoint), but it significantly improved LV function and produced a marked decrease in aldosterone levels at study end.

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Notes

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Acknowledgments

The authors are grateful to Alessandra Fionda and Daniela Angeletti, Takeda Italia Farmaceutici, for their continuous and enthusiastic support to the trial. We thank Giancarlo Giudici and Massimo Grigolon from Biosite Italy for analytical support.

Funding sources and disclosures

The CandHeart trial was supported by a grant from Takeda Italia Farmaceutici, Italy. Drs. Maggioni and Latini have received institutional research support

Author information

Authors and Affiliations

  1. Cardiovascular Department, “Ospedali Riuniti” and University of Trieste, Trieste, Italy

    Aneta Aleksova & Gianfranco Sinagra

  2. Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche “Mario Negri”, via Giuseppe La Masa 19, 20156, Milan, Italy

    Serge Masson, Lidia Staszewsky & Roberto Latini

  3. ANMCO Research Center, Florence, Italy

    Aldo P. Maggioni, Donata Lucci & Renato Urso

  4. Department of Neurological and Behavioral Science, University of Siena, Pharmacology Section, Siena, Italy

    Renato Urso

  5. Laboratory of Clinical Chemistry, Ospedale Sacro Cuore Don Calabria, Negrar, Italy

    Stefano Ciaffoni

  6. Department of Cardiovascular Diseases, San Giovanni-Addolorata Hospital, Rome, Italy

    Giuseppe Cacciatore

  7. Division of Cardiology, Ospedale Santissima Annunziata, Cosenza, Italy

    Gianfranco Misuraca

  8. Cardiology Unit, Ospedale Garibaldi-Nesima, Catania, Italy

    Michele Gulizia

  9. Cardiology Unit, Ospedale Sant’Antonio, San Daniele del Friuli, Italy

    Lucio Mos

  10. Cardiology Unit, Azienda ASL 4, Terni, Italy

    Gianni Proietti

  11. Cardiology Unit, Ospedale San Giovanni di Dio, Florence, Italy

    Calogero Minneci

Authors
  1. Aneta Aleksova
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  2. Serge Masson
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  3. Aldo P. Maggioni
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  4. Donata Lucci
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  5. Renato Urso
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  6. Lidia Staszewsky
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  7. Stefano Ciaffoni
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  8. Giuseppe Cacciatore
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  9. Gianfranco Misuraca
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  10. Michele Gulizia
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  11. Lucio Mos
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  12. Gianni Proietti
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  13. Calogero Minneci
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  14. Roberto Latini
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  15. Gianfranco Sinagra
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on the behalf of the CandHeart Investigators

Corresponding author

Correspondence to Roberto Latini.

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Aleksova, A., Masson, S., Maggioni, A.P. et al. Effects of Candesartan on Left Ventricular Function, Aldosterone and BNP in Chronic Heart Failure. Cardiovasc Drugs Ther 26, 131–143 (2012). https://doi.org/10.1007/s10557-012-6370-8

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  • DOI: https://doi.org/10.1007/s10557-012-6370-8

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