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European Journal of Heart Failure 2003 5(1):47-53; doi:10.1016/S1388-9842(02)00205-2
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© 2002 European Society of Cardiology

Neurohormonal effects of furosemide withdrawal in elderly heart failure patients with normal systolic function

Dave J.W. van Kraaija,*, René W.M.M. Jansenb, Fred C.G.J. Sweepc and Willibrord H.L. Hoefnagelsb

a Department of Cardiology, Academic Hospital Maastricht Maastricht, The Netherlands
b Department of Geriatric Medicine, University Medical Center St. Radboud Nijmegen, The Netherlands
c Department of Chemical Endocrinology, University Medical Center St. Radboud Nijmegen, The Netherlands

* Corresponding author. Department of Cardiology, University Hospital Maastricht, P.O. Box 5800, 6200 AZ Maastricht, The Netherlands. Tel.: +31-43-387-5106; fax: +31-43-387-5104 E-mail address: dvankraaij{at}hotmail.com


  Abstract

Background: In heart failure patients, diuretics cause renin–angiotensin–aldosterone system (RAS) activation, which may lead to increased morbidity and mortality despite short-term symptomatic improvement.

Aim: To determine changes in RAS activation and clinical correlates following furosemide withdrawal in elderly heart failure patients without left ventricular systolic dysfunction.

Methods and results: We performed clinical assessments and laboratory determinations of aldosterone, plasma renin activity (PRA), atrial natriuretic peptide (ANP), norepinephrine, and endothelin in 29 heart failure patients [aged 75.1±0.7 (mean±S.E.M.) years], before, 1 and 3 months after placebo-controlled furosemide withdrawal. Recurrent congestion occurred in 2 of 19 patients withdrawn, and in 1 of 10 patients continuing on furosemide. Three months after withdrawal, PRA had decreased –1.61±0.71 nmol/l/h (P<0.05). Decreases in aldosterone levels did not reach significance (–0.17±0.38 nmol/l). The decreases in PRA after withdrawal correlated with decreases in systolic (rs=0.61, P=0.020) and diastolic blood pressure (rs=0.80, P=0.01). Successful withdrawal was associated with increases in norepinephrine (+0.58±0.22 nmol/l) and ANP (+3.5±1.3 pmol/l) (P<0.05) after 1 month, but these changes did not persist after 3 months. Endothelin levels did not change in both groups.

Conclusion: Successful furosemide withdrawal in elderly heart failure patients causes persistent decreases in RAS activation.

Key Words: Aged-80-and-over • Diuretic withdrawal • Diastolic heart failure • Renin–angiotensin system • Neurohormones

Received June 29, 2001; Revised July 6, 2002; Accepted July 12, 2002


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