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Heart Failure Reviews Jan 2021Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte... (Meta-Analysis)
Meta-Analysis Review
Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte abnormalities, and acid-base disturbance. These adverse effects of diuretics predispose patients to serious cardiac arrhythmias and may increase the risk of arrhythmic mortality. Herein, we aim to summarize the relative efficacy and safety of all available diuretics used in the treatment of patients with HF. In June 2017, a systematic electronic database search was conducted in nine databases. All randomized controlled trials (RCTs) comparing the different diuretics used in HF were included for meta-analysis. The protocol was registered in Prospero with CRD42018084819. Among the included 54 studies (10,740 patients), 34 RCTs were eligible for quantitative network meta-analysis (NMA) and traditional meta-analysis while the other 20 studies were qualitatively analyzed. Our results showed that azosemide and torasemide caused a significant reduction in brain natriuretic peptide (BNP) level. Torasemide also caused a significant decrease in collagen volume fraction (CVF) and edema. No significant difference between the agents concerning glomerular filtration rate (GFR), water extraction, and sodium excretion was demonstrated. Regarding side effects, no significant difference among diuretics was observed in terms of hospital readmission and mortality rates. Diuretics are the main treatment of hypervolemia in HF patients. The choice of appropriate diuretic is essential for successful management and is mainly guided by patient clinical situations and the presence of other co-morbidities.
Topics: Diuretics; Furosemide; Heart Failure; Humans; Randomized Controlled Trials as Topic; Torsemide
PubMed: 32783109
DOI: 10.1007/s10741-020-10003-7 -
JAMA Network Open Dec 2023The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood. (Randomized Controlled Trial)
Randomized Controlled Trial
Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker: A Secondary Analysis of a Randomized Clinical Trial.
IMPORTANCE
The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood.
OBJECTIVE
To determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up.
DESIGN, SETTING, AND PARTICIPANTS
This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at least 1 other coronary heart disease risk factor for up to 23 years, from February 23, 1994, to December 31, 2017. Trial participants were linked with administrative databases for posttrial mortality (N = 32 804) and morbidity outcomes (n = 22 754). Statistical analysis was performed from January 2022 to October 2023.
INTERVENTIONS
Participants were randomly assigned to receive a thiazide-type diuretic (n = 15 002), a CCB (n = 8898), or an ACE inhibitor (n = 8904) for planned in-trial follow-up of approximately 4 to 8 years and posttrial passive follow-up for up to 23 years.
MAIN OUTCOMES AND MEASURES
The primary end point was mortality due to cardiovascular disease (CVD). Secondary outcomes included all-cause mortality, combined fatal and nonfatal (morbidity) CVD, and both mortality and morbidity for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.
RESULTS
A total of 32 804 participants (mean [SD] age, 66.9 [7.7] years; 17 411 men [53.1%]; and 11 772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22 754 participants (mean [SD] age, 68.7 [7.2] years; 12 772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]).
CONCLUSIONS AND RELEVANCE
In this secondary analysis of a randomized clinical trial in an adult population with hypertension and coronary heart disease risk factors, CVD mortality was similar between all 3 groups. ACE inhibitors increased the risk of stroke outcomes by 11% compared with diuretics, and this effect persisted well beyond the trial period.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00000542.
Topics: Adult; Male; Female; Humans; Aged; Angiotensin-Converting Enzyme Inhibitors; Diuretics; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Hypertension; Thiazides; Sodium Chloride Symporter Inhibitors; Stroke; Antiviral Agents; Coronary Disease
PubMed: 38048133
DOI: 10.1001/jamanetworkopen.2023.44998 -
Critical Care (London, England) Oct 2022Fluid overload and venous congestion are associated with morbi-mortality in the ICU (intensive care unit). Administration of diuretics to correct the fluid balance is... (Observational Study)
Observational Study
Doppler study of portal vein and renal venous velocity predict the appropriate fluid response to diuretic in ICU: a prospective observational echocardiographic evaluation.
BACKGROUND
Fluid overload and venous congestion are associated with morbi-mortality in the ICU (intensive care unit). Administration of diuretics to correct the fluid balance is common, although there is no strong relationship between the consequent fluid loss and clinical improvement. The aim of the study was to evaluate the ability of the portal pulsatility index, the renal venous impedance index, and the VEXUS score (venous ultrasound congestion score) to predict appropriate diuretic-induced fluid depletion.
METHODS
The study had a prospective, observational, single-center observational design and was conducted in a university-affiliated medico-surgical ICU. Adult patients for whom the clinician decided to introduce loop diuretic treatment were included. Hemodynamic and ultrasound measurements (including the portal pulsatility index, renal venous impedance index and VEXUS score) were performed at inclusion and 2 hours after the initiation of the diuretics. The patients' characteristics were noted at inclusion, 24 h later, and at ICU discharge. The appropriate diuretic-induced fluid depletion was defined by a congestive score lower than 3 after diuretic fluid depletion. The congestive score included clinical and biological parameters of congestion.
RESULTS
Eighty-one patients were included, and 43 (53%) patients presented with clinically significant congestion score at inclusion. Thirty-four patients (42%) had an appropriate response to diuretic-induced fluid depletion. None of the left- and right-sided echocardiographic parameters differed between the two groups. The baseline portal pulsatility index was the best predictor of appropriate response to diuretic-induced fluid depletion (AUC = 0.80, CI:0.70-0.92, p = 0.001), followed by the renal venous impedance index (AUC = 0.72, CI 0.61-0.84, p = 0.001). The baseline VEXUS score (AUC of 0.66 CI 0.53-0.79, p = 0.012) was poorly predictive of appropriate response to diuretic-induced fluid depletion.
CONCLUSION
The portal pulsatility index and the renal venous impedance index were predictive of the appropriate response to diuretic-induced fluid depletion in ICU patients. The portal pulsatility index should be evaluated in future randomized studies.
Topics: Adult; Diuretics; Echocardiography, Doppler; Humans; Intensive Care Units; Portal Vein; Prospective Studies; Sodium Potassium Chloride Symporter Inhibitors; Ultrasonography, Doppler
PubMed: 36199091
DOI: 10.1186/s13054-022-04180-0 -
Postgraduate Medical Journal Jun 2022Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%-56%... (Review)
Review
Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%-56% of hypokalaemia in patients taking thiazide diuretics. The clinical manifestations of hypokalaemia due to diuretics are non-specific, varying from asymptomatic to fatal arrhythmia. Diagnosis of hypokalaemia is based on the level of serum potassium. ECG is useful in identifying the more severe consequences. A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac arrhythmias can increase the risk of cardiovascular events and mortality. Thiazide-induced potassium depletion may cause dysglycaemia. The risk of thiazide-induced hypokalaemia is higher in women and in black people. Reducing diuretic dose and potassium supplementation are the most direct and effective therapies for hypokalaemia. Combining with a potassium-sparing diuretic or blocker of the renin-angiotensin system also reduces the risk of hypokalaemia. Lowering salt intake and increasing intake of vegetables and fruits help to reduce blood pressure as well as prevent hypokalaemia.
Topics: Arrhythmias, Cardiac; Diuretics; Female; Humans; Hypertension; Hypokalemia; Potassium; Sodium Chloride Symporter Inhibitors; Thiazides
PubMed: 33688065
DOI: 10.1136/postgradmedj-2020-139701 -
Current Opinion in Cardiology May 2024To summarize the contemporary evidence on decongestion strategies in patients with acute heart failure (AHF). (Review)
Review
PURPOSE OF REVIEW
To summarize the contemporary evidence on decongestion strategies in patients with acute heart failure (AHF).
RECENT FINDINGS
While loop diuretic therapy has remained the backbone of decongestive treatment in AHF, multiple randomized clinical trials suggest that early combination with other diuretic classes or molecules with diuretic properties should be considered. Mineralocorticoid receptor antagonists and sodium-glucose co-transporter-2 inhibitors are disease-modifying drugs in heart failure that favourably influence prognosis early on, advocating their start as soon as possible in the absence of any compelling contraindications. Short-term upfront use of acetazolamide in adjunction to intravenous loop diuretic therapy relieves congestion faster, avoids diuretic resistance, and may shorten hospitalization length. Thiazide-like diuretics remain a good option to break diuretic resistance. Currently, ultrafiltration in AHF remains mainly reserved for patient with an inadequate response to pharmacological treatment.
SUMMARY
In most patients with AHF, decongestion can be achieved effectively and safely through combination diuretic therapies. Appropriate diuretic therapy may shorten hospitalization length and improve quality of life, but has not yet proven to reduce death or heart failure readmissions. Ultrafiltration currently has a limited role in AHF, mainly as bail-out strategy, but evidence for a more upfront use remains inconclusive.
Topics: Humans; Sodium Potassium Chloride Symporter Inhibitors; Ultrafiltration; Quality of Life; Diuretics; Heart Failure; Acute Disease
PubMed: 38362936
DOI: 10.1097/HCO.0000000000001124 -
Acta Cardiologica Apr 2022In heart failure, fluid overload is a major pathological mechanism leading to vascular congestion, pulmonary congestion and elevated jugular venous pressures. Diuretics... (Review)
Review
In heart failure, fluid overload is a major pathological mechanism leading to vascular congestion, pulmonary congestion and elevated jugular venous pressures. Diuretics play a significant role in the management of patients with congestive heart failure. It is used to relieve the congestive symptoms of heart failure. However, the appropriate use of diuretics remains challenging due to various complications like electrolyte abnormalities, worsening renal function and diuretic resistance. This has prompted towards the search of safer and effective alternatives. This review evaluates the use of diuretics in congestive heart failure and discusses the complications of different types of diuretics, which is essential for successful management of congestion in patients with heart failure and hence to optimise the outcome for the patients.
Topics: Diuretics; Heart Failure; Humans
PubMed: 33653227
DOI: 10.1080/00015385.2021.1878423 -
Current Cardiology Reports Nov 2023To provide an update and review approaches to the treatment of resistant hypertension (RH) with a focus on emerging potential therapies. (Review)
Review
PURPOSE OF REVIEW
To provide an update and review approaches to the treatment of resistant hypertension (RH) with a focus on emerging potential therapies.
RECENT FINDINGS
Resistant hypertension is defined as a blood pressure that remains elevated above a patient's individualized target despite the concurrent use of 3 antihypertensive agents of different classes including a diuretic or use of 4 or more antihypertensive agents. Patients with RH have an increased risk of adverse cardiovascular and renal outcomes. Most RH is attributed to apparent RH and is not true RH. True RH is a diagnosis of exclusion after apparent RH has been excluded. Treatment of RH is challenging, and blood pressure goal is often difficult to achieve. Currently several new therapies have emerged with forthcoming data that provide promise for improved blood pressure control in those with resistant hypertension. Once RH has been diagnosed, patients should be on standardized therapy that includes agents from three different classes including a diuretic with addition in most cases of a mineralocorticoid as a fourth line agent. There are newer agents in development currently being studied in clinical trials including dual endothelin receptor antagonists and aldosterone synthase inhibitors that appear to be efficacious. Other approved medications including SGLT2 inhibitors and non-steroidal mineralocorticoids such as finerenone also need to be incorporated into treatment paradigms. Renal denervation with catheter based devices is another potential promising treatment option in this population.
Topics: Humans; Antihypertensive Agents; Hypertension; Blood Pressure; Kidney; Diuretics; Mineralocorticoid Receptor Antagonists
PubMed: 37755638
DOI: 10.1007/s11886-023-01966-8 -
Blood Purification 2020Hyponatremia is the most common electrolyte disorder encountered clinically. While acute and/or severe hyponatremia is commonly associated with significant symptoms,... (Review)
Review
BACKGROUND
Hyponatremia is the most common electrolyte disorder encountered clinically. While acute and/or severe hyponatremia is commonly associated with significant symptoms, milder and more chronic forms of hyponatremia remain clinically inconspicuous. Recent evidence suggests that even milder forms of hyponatremia are associated with increased morbidity and mortality. Despite this, currently available treatments for chronic hyponatremia lack data on efficacy and/or have important limitations related to patient nonadherence, adverse side effects, and/or significant costs. Consequently, there is a clear need for investigation of alternative treatments for this common condition.
SUMMARY
Small case series conducted in Europe since the early 1980s suggest that urea, an oral osmotic diuretic that increases urinary water excretion, is safe and effective for the treatment of chronic hyponatremia. In 2016, a novel formulation of urea became available in the United States. Our group recently reported the first and only study describing the efficacy and safety of this American formulation of oral urea among hospitalized patients with hyponatremia. Key Messages: Oral urea appears to be an effective, safe, and well-tolerated therapeutic strategy in the management of chronic hyponatremia.
Topics: Chronic Disease; Diuretics; Humans; Hyponatremia; Urea
PubMed: 31851974
DOI: 10.1159/000503773 -
Heart Failure Reviews Jan 2020Acute heart failure hospitalizations complicated by diuretic resistance are associated with worse outcomes. Yet, quantification of the frequency and accompanying risk... (Review)
Review
Acute heart failure hospitalizations complicated by diuretic resistance are associated with worse outcomes. Yet, quantification of the frequency and accompanying risk from loop diuretic resistance is limited by the absence of a comprehensive definition with universal clinical application. Herein, we outline limitations of the current metrics used to identify and define diuretic resistance. We discuss the best available methods to identify and prognosticate outcomes in diuretic resistance. We propose a mechanism-based classification system of diuretic resistance by anatomical location as follows: pre-nephron resistance, pre-loop of Henle resistance, loop of Henle resistance, and post-loop of Henle resistance. Within this paradigm, we compare and contrast historical beliefs of resistance mechanisms with current literature specific to patients with heart failure. We recommend a treatment pathway to restore diuretic efficacy with a literature review of the various combination diuretic strategies and ongoing clinical trials that may impact current best practices.
Topics: Acute Disease; Diuretics; Drug Resistance; Heart Failure; Humans; Infusions, Intravenous; Practice Guidelines as Topic; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 31520280
DOI: 10.1007/s10741-019-09851-9 -
The American Journal of the Medical... Oct 2022Diuretics are amongst the most prescribed medications in both the inpatient and outpatient settings. They are used extensively in diverse disease states including heart... (Review)
Review
Diuretics are amongst the most prescribed medications in both the inpatient and outpatient settings. They are used extensively in diverse disease states including heart failure, acute and chronic kidney disease, cirrhosis, and diseases of excess capillary permeability such as sepsis, malignancy, and malnutrition. All are characterized by total body sodium overabundance which commonly manifests as edema. The use of diuretics is however not bereft of complications. These complications frequently limit the correction of hypervolemia, resulting in continued patient suffering and frustration for the clinician. In this review, we employ a case-based approach to discuss three common challenges encountered during diuretic therapy: diuretic resistance that characterizes the nephrotic syndrome, diuretic-induced metabolic alkalosis, and diuretic-associated hyponatremia. We empower the clinician to effectively meet these challenges by providing a mechanistic understanding of these complications and their solutions.
Topics: Diuretics; Edema; Heart Failure; Humans; Hyponatremia; Sodium
PubMed: 35472337
DOI: 10.1016/j.amjms.2022.04.021