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


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


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 Recurrent congestion occurred in 2 of 19 patients withdrawn, and in 1 of 10 patients continuing on furosemide.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.


CONCLUSIONS
Successful furosemide withdrawal in elderly heart failure patients causes persistent decreases in RAS activation.
van Kraaij
Dave J W
DJ
Department of Cardiology, Academic Hospital Maastricht, Maastricht, The Netherlands. dvankraaij@hotmail.com
Jansen
René W M M
RW
Sweep
Fred C G J
FC
Hoefnagels
Willibrord H L
WH
D000368:Aged; D000450:Aldosterone / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004232:Diuretics / Q000009:adverse effects*; D004311:Double-Blind Method; D004452:Echocardiography; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005665:Furosemide / Q000009:adverse effects*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010349:Patient Compliance; D012083:Renin / Q000097:blood / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D013223:Statistics as Topic; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D013599:Systole / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D018377:Neurotransmitter Agents; D000450:Aldosterone; D005665:Furosemide; D009320:Atrial Natriuretic Factor; D012083:Renin; D009638:Norepinephrine; D004837:Epinephrine