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 Recurrent congestion occurred in 2 of 19 patients withdrawn, and in 1 of 10 patients continuing on furosemide.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 (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 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.
RCT Entities:
BACKGROUND: In heart failurepatients, 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 failurepatients 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 failurepatients [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 Recurrent congestion occurred in 2 of 19 patients withdrawn, and in 1 of 10 patients continuing on furosemide.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 (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 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 failurepatients causes persistent decreases in RAS activation.
Authors: Amy T Page; Rhonda M Clifford; Kathleen Potter; Darren Schwartz; Christopher D Etherton-Beer Journal: Br J Clin Pharmacol Date: 2016-06-13 Impact factor: 4.335
Authors: David Montero; Thomas Haider; Jens Barthelmes; Jens P Goetze; Silviya Cantatore; Isabella Sudano; Frank Ruschitzka; Andreas J Flammer Journal: Physiol Rep Date: 2019-11