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 waged 75.1"0.7 (mean"S.E.M.) yearsx, 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 Recurrent congestion occurred in 2 of 19 patients withdrawn, and in 1 of 10 patients continuing on furosemide.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 y1.61"0.71 nmolylyh (P-0.05). Decreases in aldosterone levels did not reach significance (y0.17"0.38 nmolyl). The decreases in PRA after withdrawal correlated with decreases in systolic (r s0.61, Ps0.020) and diastolic blood pressure s (r s0.80, Ps0.01). Successful withdrawal was associated with increases in norepinephrine (q0.58"0.22 nmolyl) and ANP (q s 3.5"1.3 pmolyl) (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.