-
European Journal of Heart Failure Feb 2019The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those... (Review)
Review
The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion.
Topics: Cardiology; Consensus; Diuretics; Europe; Heart Failure; Humans; Societies, Medical; Stroke Volume
PubMed: 30600580
DOI: 10.1002/ejhf.1369 -
Journal of the American College of... Mar 2020Expansion of extracellular fluid volume is central to the pathophysiology of heart failure. Increased extracellular fluid leads to elevated intracardiac filling... (Review)
Review
Expansion of extracellular fluid volume is central to the pathophysiology of heart failure. Increased extracellular fluid leads to elevated intracardiac filling pressures, resulting in a constellation of signs and symptoms of heart failure referred to as congestion. Loop diuretics are one of the cornerstones of treatments for heart failure, but in contrast to other therapies, robust clinical trial evidence to guide the use of diuretics is sparse. A nuanced understanding of renal physiology and diuretic pharmacokinetics is essential for skillful use of diuretics in the management of heart failure in both the inpatient and outpatient settings. Diuretic resistance, defined as an inadequate quantity of natriuresis despite an adequate diuretic regimen, is a major clinical challenge that generally portends a poor prognosis. In this review, the authors discuss the fundamental mechanisms and physiological principles that underlie the use of diuretic therapy and the available data on the optimal use of diuretics.
Topics: Diuretics; Gastrointestinal Absorption; Heart Failure; Humans; Kidney; Review Literature as Topic; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 32164892
DOI: 10.1016/j.jacc.2019.12.059 -
European Heart Journal Feb 2023To evaluate whether the addition of hydrochlorothiazide (HCTZ) to intravenous furosemide is a safe and effective strategy for improving diuretic response in acute heart... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
To evaluate whether the addition of hydrochlorothiazide (HCTZ) to intravenous furosemide is a safe and effective strategy for improving diuretic response in acute heart failure (AHF).
METHODS AND RESULTS
A prospective, double-blind, placebo-controlled trial, including patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The coprimary endpoints were changes in body weight and patient-reported dyspnoea 72 h after randomization. Secondary outcomes included metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. Safety outcomes (changes in renal function and/or electrolytes) were also assessed. Two hundred and thirty patients (48 women, 83 years) were randomized. Patients assigned to HCTZ were more likely to lose weight at 72 h than those assigned to placebo [2.3 vs. 1.5 kg; adjusted estimated difference (notionally 95 confidence interval) 1.14 (1.84 to 0.42); P 0.002], but there were no significant differences in patient-reported dyspnoea (area under the curve for visual analogue scale: 960 vs. 720; P 0.497). These results were similar 96 h after randomization. Patients allocated to HCTZ showed greater 24 h diuresis (1775 vs. 1400 mL; P 0.05) and weight loss for each 40 mg of furosemide (at 72 and at 96 h) (P 0.001). Patients assigned to HCTZ more frequently presented impaired renal function (increase in creatinine 26.5 moL/L or decrease in eGFR 50; 46.5 vs. 17.2; P 0.001), but hypokalaemia and hypokalaemia were similar between groups. There were no differences in mortality or rehospitalizations.
CONCLUSION
The addition of HCTZ to loop diuretic therapy improved diuretic response in patients with AHF.
Topics: Humans; Female; Furosemide; Sodium Chloride Symporter Inhibitors; Hypokalemia; Prospective Studies; Heart Failure; Diuretics; Hydrochlorothiazide; Dyspnea
PubMed: 36423214
DOI: 10.1093/eurheartj/ehac689 -
American Journal of Kidney Diseases :... Aug 2022Volume overload, defined as excess total body sodium and water with expansion of extracellular fluid volume, characterizes common disorders such as congestive heart... (Review)
Review
Volume overload, defined as excess total body sodium and water with expansion of extracellular fluid volume, characterizes common disorders such as congestive heart failure, end-stage liver disease, chronic kidney disease, and nephrotic syndrome. Diuretics are the cornerstone of therapy for volume overload and comprise several classes whose mechanisms of action, pharmacokinetics, indications, and adverse effects are essential principles of nephrology. Loop diuretics are typically the first-line treatment in the management of hypervolemia, with additional drug classes indicated in cases of diuretic resistance and electrolyte or acid-base disorders. Separately, clinical trials highlight improved outcomes in some states of volume overload, such as loop diuretics and sodium/glucose cotransporter 2 inhibitors in patients with congestive heart failure. Resistance to diuretics is a frequent, multifactorial clinical challenge that requires creative and physiology-based solutions. In this installment of AJKD's Core Curriculum in Nephrology, we discuss the pharmacology and therapeutic use of diuretics in states of volume overload and strategies to overcome diuretic resistance.
Topics: Acid-Base Imbalance; Curriculum; Diuretics; Heart Failure; Humans; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Water-Electrolyte Imbalance
PubMed: 35190215
DOI: 10.1053/j.ajkd.2021.09.029 -
European Journal of Pediatrics May 2023Diuretics are frequently prescribed drugs and help managing several pathological conditions, including acute and chronic kidney disease, nephrotic syndrome, congestive... (Review)
Review
UNLABELLED
Diuretics are frequently prescribed drugs and help managing several pathological conditions, including acute and chronic kidney disease, nephrotic syndrome, congestive heart failure, ascites, systemic and pulmonary hypertension. Diuretic classes include among others osmotic diuretics and carboanhydrase inhibitors, loop diuretics, thiazides, and potassium-sparing diuretics. In this educational article, we aim at reviewing indications, mechanisms of action, and side effects, as well as basic pharmacokinetics considerations and data on diuretics in children, supporting practicing clinicians in choosing (and understanding the background of) the best-suited diuretic regimen for the individual patient. Newer diuretic classes like vaptans and sodium glucose type 2 cotransporter inhibitors, the recent controversies on hydrochlorothiazide, and the issue of diuretic resistance, will also be briefly addressed.
CONCLUSION
This educational review offers a didactical overview of diuretics in Pediatrics.
WHAT IS KNOWN
• Diuretics are frequently prescribed drugs in both adults and children. • They increase water and sodium excretion, reducing fluid overload.
WHAT IS NEW
• This article reviews indications, mechanisms of action, side effects, and basic pharmacokinetics facts on diuretics in Paediatrics. • It also addresses current issues, like the management of diuretic resistance, the recent controversy on hydrochlorothiazide, and the novel classes vaptans and gliflozins.
Topics: Adult; Humans; Child; Diuretics; Hydrochlorothiazide; Sodium Potassium Chloride Symporter Inhibitors; Sodium; Heart Failure
PubMed: 36595088
DOI: 10.1007/s00431-022-04768-2 -
Journal of the American College of... Jan 2023Heart failure (HF) is a progressive disease characterized by variable durations of symptomatic stability often punctuated by episodes of worsening despite continued... (Review)
Review
Heart failure (HF) is a progressive disease characterized by variable durations of symptomatic stability often punctuated by episodes of worsening despite continued therapy. These periods of clinical worsening are increasingly recognized as a distinct phase in the history of HF, termed worsening HF (WHF). The definition of WHF continues to evolve from a historical focus solely on hospitalization to now include nonhospitalization events (eg, need for intravenous diuretic therapy in the emergency or outpatient setting). Most HF clinical trials to date have had HF hospitalization and death as primary endpoints, and only recently, some studies have included other WHF events regardless of location of care. This article reviews the evolution of the WHF definition, highlights the importance of considering the onset of WHF as an event that marks a new phase of HF, summarizes the latest clinical trials investigating novel therapies, and outlines unmet needs regarding identification and treatment of WHF.
Topics: Humans; Acute Disease; Disease Progression; Diuretics; Heart Failure; Hospitalization
PubMed: 36697141
DOI: 10.1016/j.jacc.2022.11.023 -
Current Heart Failure Reports Apr 2019Diuretic resistance (DR) occurs along a spectrum of relative severity and contributes to worsening of acute heart failure (AHF) during an inpatient stay. This review... (Review)
Review
PURPOSE OF REVIEW
Diuretic resistance (DR) occurs along a spectrum of relative severity and contributes to worsening of acute heart failure (AHF) during an inpatient stay. This review gives an overview of mechanisms of DR with a focus on loop diuretics and summarizes the current literature regarding the prognostic value of diuretic efficiency and predictors of natriuretic response in AHF.
RECENT FINDINGS
The pharmacokinetics of diuretics are impaired in chronic heart failure, but little is known about mechanisms of DR in AHF. Almost all diuresis after administration of a loop diuretic dose occurs in the first few hours after administration and within-dose DR can develop. Recent studies suggest that DR at the level of the nephron may be more important than defects in diuretic delivery to the tubule. Because loop diuretics induce natriuresis, urine sodium (UNa) concentration may serve as a functional, physiological, and direct measure for diuretic responsiveness to a given loop diuretic dose. Identifying and targeting individuals with DR for more aggressive, tailored therapy represents an important opportunity to improve outcomes. A better understanding of the mechanistic underpinnings of DR in AHF is needed to identify additional biomarkers and guide future trials and therapies.
Topics: Diuretics; Drug Resistance; Heart Failure; Humans; Nephrons; Prognosis; Sodium; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 30762178
DOI: 10.1007/s11897-019-0424-1 -
Pediatric Nephrology (Berlin, Germany) Dec 2016Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of... (Review)
Review
Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of diuretics may be useful in alternative circumstances. Although diuretics are no longer considered the preferred agent for treatment of hypertension in adults and children, they remain acceptable first-line options. Diuretics effectively decrease blood pressure in hypertensive patients, and in adults with hypertension reduce the risk of adverse cardiovascular outcomes. Because of varied pharmacokinetic and pharmacodynamic differences, chlorthalidone may be the preferred thiazide diuretic in the treatment of primary hypertension. Other types of diuretics (e.g., loop, potassium sparing) may be useful for the treatment of hypertension related to chronic kidney disease (CKD) and other varied conditions. Common side effects of thiazides are mostly dose-related and involve electrolyte and metabolic abnormalities.
Topics: Adolescent; Antihypertensive Agents; Child; Child, Preschool; Diuretics; Guidelines as Topic; Humans; Hypertension; Infant; Infant, Newborn; Thiazides
PubMed: 26983630
DOI: 10.1007/s00467-016-3334-4 -
Naunyn-Schmiedeberg's Archives of... Jun 2022Diuretics are drugs that increase the flow of urine. They are commonly used to treat edema, hypertension, and heart failure. Typically, the pharmacological group... (Review)
Review
Diuretics are drugs that increase the flow of urine. They are commonly used to treat edema, hypertension, and heart failure. Typically, the pharmacological group consists of five classes: thiazide diuretics, loop diuretics, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors. This traditional classification and the nomenclature of diuretics have not changed over the last decades, which means that it was not adapted to current pharmacological research. Modern approaches in the field of pharmacological nomenclature suggest the introduction of mechanism-based drug class designations, which is not yet reflected in the group of diuretics. Moreover, included drug classes have lost their relevance as diuretic agents. Carbonic anhydrase inhibitors, for example, are mainly used in the treatment of glaucoma. Newer agents such as vasopressin-2 receptor antagonists or SGLT2 inhibitors possess diuretic properties but are not included in the pharmacological group. This review discusses the currentness of the pharmacological classification of diuretics. We elaborate changes in the field of nomenclature, the contemporary medical use of classical diuretics, and new diuretic agents.
Topics: Carbonic Anhydrase Inhibitors; Diuretics; Heart Failure; Humans; Hypertension; Sodium Chloride Symporter Inhibitors
PubMed: 35294605
DOI: 10.1007/s00210-022-02228-0 -
The New England Journal of Medicine Mar 2023Nephrolithiasis is one of the most common conditions affecting the kidney and is characterized by a high risk of recurrence. Thiazide diuretic agents are widely used for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Nephrolithiasis is one of the most common conditions affecting the kidney and is characterized by a high risk of recurrence. Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited. Furthermore, dose-response data are also limited.
METHODS
In this double-blind trial, we randomly assigned patients with recurrent calcium-containing kidney stones to receive hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. The main objective was to investigate the dose-response effect for the primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Radiologic recurrence was defined as the appearance of new stones on imaging or the enlargement of preexisting stones that had been observed on the baseline image. Safety was also assessed.
RESULTS
In all, 416 patients underwent randomization and were followed for a median of 2.9 years. A primary end-point event occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio vs. placebo, 1.33; 95% confidence interval [CI], 0.92 to 1.93), in 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and in 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36). There was no relation between the hydrochlorothiazide dose and the occurrence of a primary end-point event (P = 0.66). Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and a plasma creatinine level exceeding 150% of the baseline level were more common among patients who received hydrochlorothiazide than among those who received placebo.
CONCLUSIONS
Among patients with recurrent kidney stones, the incidence of recurrence did not appear to differ substantially among patients receiving hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily. (Funded by the Swiss National Science Foundation and Inselspital; NOSTONE ClinicalTrials.gov number, NCT03057431.).
Topics: Humans; Hydrochlorothiazide; Kidney; Kidney Calculi; Sodium Chloride Symporter Inhibitors; Recurrence; Double-Blind Method; Dose-Response Relationship, Drug; Diuretics
PubMed: 36856614
DOI: 10.1056/NEJMoa2209275