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

Background: In heart failure patients, diuretics cause renin-atigiotensin-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, I and 3 months after placebo-controlled furosemide withdrawal. Recurrent congestion occurred in 2 of 19 patients withdrawn, and in I of 10 patients continuing on furosemide.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 (r(s) = 0.61, P = 0.020) and diastolic blood pressure (r(s) = 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 I 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. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.