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Journal of the American College of... Feb 2015Hyponatremia frequently poses a therapeutic challenge in acute decompensated heart failure (ADHF). Treating physicians should differentiate between depletional versus... (Comparative Study)
Comparative Study Review
Hyponatremia frequently poses a therapeutic challenge in acute decompensated heart failure (ADHF). Treating physicians should differentiate between depletional versus dilutional hyponatremia. The former is caused by diuretic agents, which enhance sodium excretion, often with concomitant potassium/magnesium losses. This can be treated with isotonic saline, whereas potassium/magnesium administration may be helpful if plasma concentrations are low. In contrast, as impaired water excretion, rather than sodium deficiency, is the culprit in dilutional hyponatremia, isotonic saline administration may further depress the serum sodium concentration. Because free water excretion is achieved by continuous sodium reabsorption in distal nephron segments with low water permeability, diuretic agents that impair this mechanism (e.g., thiazide-type diuretic agents and mineralocorticoid receptor antagonists) should be avoided, and proximally acting agents (e.g., acetazolamide and loop diuretic agents) are preferred. Vasopressin antagonists, which promote low water permeability in the collecting ducts and, hence, free water excretion, remain under investigation for dilutional hyponatremia in ADHF.
Topics: Acute Disease; Animals; Arginine Vasopressin; Diuretics; Heart Failure; Humans; Hyponatremia; Mineralocorticoid Receptor Antagonists; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 25660927
DOI: 10.1016/j.jacc.2014.12.010 -
Current Heart Failure Reports Apr 2024Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in... (Review)
Review
PURPOSE OF REVIEW
Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion-loop diuretics-has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and the current trial evidence for different diuretic strategies and explore potential future directions of research.
RECENT FINDINGS
We will assess recent trials including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF amongst others, and assess how these may influence current practice and future research. There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for high dose loop diuretic treatment over low-dose treatment for patients admitted to hospital with HF, yet this is not reflected in guidelines. There is an urgent need for more and better research on different diuretic strategies in patients with HF.
Topics: Humans; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Quality of Life; Diuretics; Hospitalization
PubMed: 38240883
DOI: 10.1007/s11897-024-00643-3 -
ESC Heart Failure Dec 2022Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a...
AIMS
Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a fundamental action of ANP in acute heart failure (AHF), whereas the diuretic effect of ANP is different in each patient according to the diversity of renal response to ANP, which is affected by baseline plasma ANP status and deficiency of circulating ANP. Meanwhile, associations between other neuroendocrine hormones and the diuretic response to ANP are unclear. This study investigated the impact of pivotal neuroendocrine hormones on the diuretic effects of exogenous ANP, carperitide.
METHODS AND RESULTS
Plasma ANP, renin, aldosterone, and vasopressin levels and the diuretic effect of 0.0125 μg/kg/min of carperitide alone for the first 6 h were prospectively evaluated in 75 patients with AHF. Lower ANP levels were significantly associated with a greater diuretic response to exogenous ANP (r = -0.35, P = 0.002). Additionally, higher vasopressin levels were significantly related to the poor diuretic effects of exogenous ANP (r = -0.54, P < 0.001). Plasma ANP and vasopressin concentrations were not significantly correlated (r = 0.19, P = 0.10). Baseline systolic blood pressure, renal function, and prior use of loop diuretics did not predict the diuretic response to exogenous ANP, whereas vasopressin levels independently predicted a diuretic response to exogenous ANP (P < 0.001), as well as lower plasma ANP levels (P = 0.027).
CONCLUSIONS
Vasopressin status was significantly associated with the diuretic response to exogenous ANP in AHF, independent of plasma ANP status. The results may provide a better understanding of the actions of sacubitril/valsartan.
Topics: Humans; Atrial Natriuretic Factor; Diuretics; Heart Failure; Valsartan; Vasopressins; Neurosecretory Systems
PubMed: 36043451
DOI: 10.1002/ehf2.14083 -
BioMed Research International 2019is a well-known traditional Chinese medicine and used as an agent for diuresis in China for centuries. This is the first time to evaluate the diuretic activity of the...
is a well-known traditional Chinese medicine and used as an agent for diuresis in China for centuries. This is the first time to evaluate the diuretic activity of the ethanol extract of (LS) and its four fractions (LSA, LSB, LSC, and LSD) in normal rats. After the administration of LS-H, LS-M, LSB-H, and LSC-L, the urine output of the rats was significantly increased, while the urine excretion was significantly reduced after treatment with LSB-L. The urine Na excretion was remarkably increased with LS-H, LS-M, LSA-H, LSA-L, LSB-H, LSC-L, and LSD-L, and the urine K excretion was significantly increased after administration of LS-H and LSB-H. Moreover, the urine Na and K excretion was significantly reduced after treatment with LSC-H and LSD-H. However, the urine pH values and urine and serum Na-K-ATPase levels did not show remarkable change after administration of LS or its four fractions in comparison with the control group. On the contrary, LS and its four fractions can suppress the renin-angiotensin-aldosterone system (RAAS), including ADH arrest by LSB-H, LSB-L, LSC-L, LSD-L, and LSD-H and ALD arrest by LSD-L, as well as promote ANP release by LS-M, LSB-H, LSC-H, and LSD-H, while furosemide can suppress only arrest of ADH within 24 h compared with the control group. In addition, LS and its four fractions did not change the urine and serum TNF- and IL-6 levels in normal rats within 24 h. This study will provide a quantitative basis for explaining the natural medicinal use of LS as a diuretic agent for edema and promoting the diuretic process.
Topics: Animals; Antidiuretic Agents; Diuretics; Lamiaceae; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Sodium; Urinalysis; Urination
PubMed: 31886241
DOI: 10.1155/2019/6927374 -
The Cochrane Database of Systematic... Jan 2007Diuretics are used to reduce blood pressure and oedema in non-pregnant individuals. Formerly, they were used in pregnancy with the aim of preventing or delaying the... (Review)
Review
BACKGROUND
Diuretics are used to reduce blood pressure and oedema in non-pregnant individuals. Formerly, they were used in pregnancy with the aim of preventing or delaying the development of pre-eclampsia. This practice became controversial when concerns were raised that diuretics may further reduce plasma volume in women with pre-eclampsia, thereby increasing the risk of adverse effects on the mother and baby, particularly fetal growth.
OBJECTIVES
To assess the effects of diuretics on prevention of pre-eclampsia and its complications.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 2) and EMBASE (2002 to April 2005).
SELECTION CRITERIA
Randomised trials evaluating the effects of diuretics for preventing pre-eclampsia and its complications.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected trials for inclusion and extracted data. We analysed and double checked data for accuracy.
MAIN RESULTS
Five studies (1836 women) were included. All were of uncertain quality. The studies compared thiazide diuretics with either placebo or no intervention. There were no clear differences between the diuretic and control groups for any reported pregnancy outcomes including pre-eclampsia (four trials, 1391 women; relative risk (RR) 0.68, 95% confidence interval (CI) 0.45 to 1.03), perinatal death (five trials,1836 women; RR 0.72, 95% CI 0.40 to 1.27), and preterm birth (two trials, 465 women; RR 0.67, 95% CI 0.32 to 1.41). There were no small-for-gestational age babies in the one trial that reported this outcome, and there was insufficient evidence to demonstrate any clear differences between the two groups for birthweight (one trial, 20 women; weighted mean difference 139 grams, 95% CI -484.40 to 762.40). Thiazide diuretics were associated with an increased risk of nausea and vomiting (two trials, 1217 women; RR 5.81, 95% CI 1.04 to 32.46), and women allocated diuretics were more likely to stop treatment due to side-effects compared to those allocated placebo (two trials, 1217 women; RR 1.85, 95% CI 0.81 to 4.22).
AUTHORS' CONCLUSIONS
There is insufficient evidence to draw reliable conclusions about the effects of diuretics on prevention of pre-eclampsia and its complications. However, from this review, no clear benefits have been found from the use of diuretics to prevent pre-eclampsia. Taken together with the level of adverse effects found, the use of diuretics for the prevention of pre-eclampsia and its complications cannot be recommended.
Topics: Diuretics; Female; Humans; Pre-Eclampsia; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 17253507
DOI: 10.1002/14651858.CD004451.pub2 -
European Journal of Heart Failure Sep 2020It is unclear whether spironolactone reduced heart failure (HF) hospitalizations in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone...
AIMS
It is unclear whether spironolactone reduced heart failure (HF) hospitalizations in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial through potential diuretic or other effects. We examined the effects of spironolactone on weight, diuretic use, and renal function, and their subsequent impact on outcomes.
METHODS AND RESULTS
We analysed data from TOPCAT Americas (1767 patients with HF and preserved ejection fraction; 886 in spironolactone, 881 in placebo arm). We used mixed-effects models for serial data and shared frailty models to identify determinants of recurrent HF hospitalizations among baseline and serial parameters. There were 800 HF hospitalizations after a median of 3.0 years. Despite more weight loss with spironolactone initially, weight trajectories overlapped after 12 months. Daily furosemide dose (time-averaged Δ: -4.8% vs. +11.6%, P < 0.001) and thiazide use (-4.3% vs. +1.7%; P = 0.003) decreased with spironolactone; however, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use decreased also (-13.1% vs. -7.3%; P = 0.004). Serum creatinine increased more with spironolactone (+12.5% vs. +3.5%; P < 0.001). In time-updated models, loop diuretic dose [hazard ratio (HR) per doubling 1.21; 95% confidence interval (CI) 1.10-1.32; P < 0.001], creatinine (HR per doubling 1.28; 95% CI 1.04-1.40; P = 0.019), and ACEI/ARB use (HR 0.82; 95% CI 0.67-1.00; P = 0.048) were associated with HF hospitalizations. However, the effect of spironolactone on HF hospitalizations persisted (HR 0.77; 95% CI 0.62-0.96; P = 0.021) in these models. Results were similar for cardiovascular mortality and time to first HF hospitalization.
CONCLUSIONS
In TOPCAT Americas, the benefit of spironolactone on outcomes could not be solely attributed to potential diuretic effects, suggesting the presence of non-diuretic mechanisms.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diuretics; Heart Failure; Hospitalization; Humans; Mineralocorticoid Receptor Antagonists; Spironolactone; Stroke Volume; Treatment Outcome
PubMed: 32469156
DOI: 10.1002/ejhf.1917 -
International Journal of Cardiology Mar 2023In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF)... (Review)
Review
BACKGROUND
In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients' clinical stability is warranted.
METHODS
The EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months. Cox proportional hazards and mixed-effects models were used for analyses.
RESULTS
Three hundred patients were included (mean age, 67 ± 13 years; 73% males). The median furosemide equivalent dose was 40 (20-62) mg at randomization. Patients with higher furosemide-equivalent doses had more severe signs and symptoms of congestion and a higher risk of all-cause mortality or HF hospitalization during 6-month follow-up (adjusted-hazard ratio per 10 mg/day increase = 1.25, 95% confidence interval: 1.05-1.49). Eplerenone significantly decreased furosemide-equivalent diuretic doses and b-type natriuretic levels throughout the follow-up (overall-joint-p < 0.05 for both) and reduced E/e' and inferior vena cava diameter at 4 weeks (both p < 0.05). Additionally, eplerenone significantly reduced left ventricular (LV) end-diastolic diameter at 24 weeks (p < 0.05).
CONCLUSIONS
Eplerenone treatment improved the clinical stability particularly during short period following hospitalization for AHF, translated by lower diuretic doses, natriuretic peptide levels, indirect markers of filling pressure and venous congestion, and a smaller LV volume.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Diuretics; East Asian People; Eplerenone; Furosemide; Heart Failure; Mineralocorticoid Receptor Antagonists; Treatment Outcome
PubMed: 36586516
DOI: 10.1016/j.ijcard.2022.12.045 -
The Cochrane Database of Systematic... Jul 2006Ménière's disease is a disorder characterised by hearing loss, tinnitus and disabling vertigo. Diuretics are used to try and reduce the severity and frequency of... (Review)
Review
BACKGROUND
Ménière's disease is a disorder characterised by hearing loss, tinnitus and disabling vertigo. Diuretics are used to try and reduce the severity and frequency of episodes but there is little evidence behind this treatment.
OBJECTIVES
To assess the effect of diuretic treatment in patients with Ménière's disease.
SEARCH STRATEGY
We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2005), MEDLINE (1966 to 2005), EMBASE (1974 to 2005), CINAHL and the metaRegister of Controlled Trials (mRCT) (up to 2005).
SELECTION CRITERIA
Randomised controlled trials of diuretic versus placebo in Ménière's patients.
DATA COLLECTION AND ANALYSIS
One author identified studies which loosely met the inclusion criteria and full texts were retrieved. Two authors independently applied the inclusion criteria. Seven studies were excluded from the review due to inappropriate study design or absence of randomisation.
MAIN RESULTS
There were no trials of high enough quality to meet the standard set for this review.
AUTHORS' CONCLUSIONS
There is insufficient good evidence of the effect of diuretics on vertigo, hearing loss, tinnitus or aural fullness in clearly defined Ménière's disease.
Topics: Diuretics; Humans; Meniere Disease; Syndrome; Tinnitus
PubMed: 16856015
DOI: 10.1002/14651858.CD003599.pub2 -
Cardiology in ReviewReversal of cardiogenic shock depends on its early recognition and prompt initiation of therapy. Recognition of the clinical and hemodynamic deterioration that precedes...
Reversal of cardiogenic shock depends on its early recognition and prompt initiation of therapy. Recognition of the clinical and hemodynamic deterioration that precedes cardiogenic shock is a crucial step in its early detection. Treatment of pre-cardiogenic shock is chiefly pharmacologic with intravenous administration of pressor, inotropic, and loop diuretic agents. Failure to reverse the preshock state with pharmacotherapy entails progression to cardiogenic shock and the need for prompt mechanical circulatory support with membrane oxygenation and possibly left ventricular decompression.
Topics: Humans; Shock, Cardiogenic; Vasoconstrictor Agents; Heart-Assist Devices; Hemodynamics; Diuretics
PubMed: 36730923
DOI: 10.1097/CRD.0000000000000485 -
European Journal of Heart Failure Jan 2023As sacubitril/valsartan may potentiate early natriuresis, expert consensus documents recommend diuretic dose reduction on first initiation. However, there are limited... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
As sacubitril/valsartan may potentiate early natriuresis, expert consensus documents recommend diuretic dose reduction on first initiation. However, there are limited data on the effects of sacubitril/valsartan on the background of varying diuretic regimens or on diuretic requirements over time in heart failure (HF) with preserved ejection fraction (HFpEF).
METHODS AND RESULTS
In this post hoc analysis of PARAGON-HF, of the 4796 patients, background diuretic therapy was distributed as follows: 341 (7%) on no diuretic, 698 (15%) on non-loop diuretic, and 3757 (78%) were on loop diuretics (1255, 1589, and 913 were on <40, 40 and >40 mg furosemide equivalent doses, respectively). The primary composite outcome of total HF hospitalizations and cardiovascular death was analysed using semiparametric proportional rates methods. The cumulative incidence of the primary composite outcome (first events) was lowest in patients on no diuretic and highest in those on >40 mg of loop diuretic (p < 0.001). The effects of sacubitril/valsartan (vs. valsartan) on the primary composite outcome (recurrent events) did not significantly vary by baseline diuretic use (p = 0.65). Treatment effects on safety outcomes were similar across diuretic categories. Sacubitril/valsartan reduced new loop diuretic initiations over the course of the trial (hazard ratio 0.83; 95% confidence interval 0.68-1.00, p = 0.055), with similar mean loop diuretic dose and rates of diuretic discontinuation between treatment groups in follow-up. Patients randomized to sacubitril/valsartan experienced a slight early reduction in diuretic initiation or dose escalation at 30 days after initiation (net reduction 1.7%, p = 0.02), but these differences were not sustained beyond this timepoint.
CONCLUSIONS
Patients with HFpEF on higher baseline diuretic doses were at heightened risk of HF events, but similarly benefited from sacubitril/valsartan with a consistent safety profile across a range of diuretic doses. Initiation of sacubitril/valsartan was associated with modestly lower new loop diuretic requirement in follow-up.
Topics: Humans; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Tetrazoles; Angiotensin Receptor Antagonists; Valsartan; Aminobutyrates; Biphenyl Compounds; Furosemide; Drug Combinations; Diuretics
PubMed: 36181769
DOI: 10.1002/ejhf.2703