Effects of Candesartan on Left Ventricular Function, Aldosterone and BNP in Chronic Heart Failure
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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.
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.
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.
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.
Key wordsHeart failure Aldosterone Natriuretic peptide Left ventricular ejection fraction Candesartan
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
- 6.Cohn JN, Anand IS, Latini R, Masson S, Chiang YT, Glazer R, Valsartan Heart Failure Trial Investigators. Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial. Circulation. 2003;108:1306–9.PubMedCrossRefGoogle Scholar
- 12.Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of European Society of Cardiology, Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008;29:2388–2442.Google Scholar
- 14.Latini R, Masson S, Anand I, et al. Valsartan Heart Failure Trial Investigators. Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure: the Valsartan Heart Failure Trial (Val-HeFT). Circulation. 2002;106:2454–8.PubMedCrossRefGoogle Scholar
- 16.Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K, Candesartan in Heartfailure Assessment of Reduction in Mortality and morbidity (CHARM) Investigators and Committees. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004;110:2618–26.PubMedCrossRefGoogle Scholar
- 17.McKelvie RS, Yusuf S, Pericak D, Avezum A, Burns RJ, Probstfield J, Tsuyuki RT, White M, Rouleau J, Latini R, Maggioni A, Young J, Pogue J. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation. 1999;100:1056–64.PubMedGoogle Scholar
- 20.R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2008. ISBN 3-900051-07-0.Google Scholar
- 21.Harrell Jr. FE. Design: design package, 2007. R package version 2.1-1.Google Scholar
- 22.Frank E Harrell Jr, with contributions from many other users. Hmisc:Harrell Miscellaneous, 2007. R package version 3.4-3, xtable David B. Dahl with contributions from many others. xtable: Export tablestoLaTeX or HTML, 2007. R package version 1.5-2.Google Scholar
- 23.Brian Ripley, from 1999 to Oct 2002 Michael Lapsley. RODBC: ODBC database access, 2009. R package version 1.3-0.Google Scholar
- 24.John Fox, with contributions from Michael Ash, Theophilius Boye, Stefano Calza, Andy Chang, Philippe Grosjean, Richard Heiberger, G. Jay Kerns, Renaud Lancelot, MatthieuLesno, Samir Messad, Martin Maechler, Duncan Murdoch, Erich Neuwirth, Dan Putler, Brian Ripley, MiroslavRistic, and Peter Wolf. Rcmdr: R Commander, 2008. R package version 1.3–15.Google Scholar
- 27.Røsjø H, Masson S, Latini R, Flyvbjerg A, Milani V, La Rovere MT, Revera M, Mezzani A, Tognoni G, Tavazzi L, Omland T, GISSI-HF Investigators. Prognostic value of chromogranin A in chronic heart failure: data from the GISSI-Heart Failure trial. Eur J Heart Fail. 2010;12:549–56.PubMedCrossRefGoogle Scholar