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Journal of the American Heart... Dec 2022Background We hypothesized that stroke outcome is related to multiple baseline hydration-related factors including volume contracted state (VCS) and diuretic use....
Background We hypothesized that stroke outcome is related to multiple baseline hydration-related factors including volume contracted state (VCS) and diuretic use. Methods and Results We analyzed a prospective cohort of subjects with ischemic stroke <24 hours of onset enrolled in acute treatment trials within VISTA (Virtual International Stroke Trials Archive). A VCS was defined based on blood urea nitrogen-to-creatinine ratio. The primary end point was modified Rankin Scale score at 90 days. Primary analysis used generalized ordinal logistic regression over the mRS range, adjusted for Totaled Health Risks in Vascular Events score, onset-to-enrollment time, and thrombolytic use. Of 5971 eligible patients with stroke, 42% were taking diuretics at the time of hospitalization, and 44% were in a VCS. Patients in a VCS were older, had more vascular risk factors, were more likely taking diuretics, and had more severe strokes. Diuretic use was associated with both reduced chance of achieving a good functional outcome (odds ratio [OR], 0.57 [95% CI, 0.52-0.63]) and increased mortality at 90 days (OR, 2.30 [95% CI, 2.04-2.61]). VCS was associated with greater mortality 90 days after stroke (OR, 1.53 [95% CI, 1.33-1.76]). There was no evidence of effect modification among the 3 exposures of VCS, diuretic use, or hypokalemia in relation to outcome. Conclusions A VCS at the time of hospitalization was associated with more severe stroke and odds of death but not associated with worse functional outcome when accounting for relevant characteristics. Diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.
Topics: Humans; Prospective Studies; Diuretics; Stroke; Fibrinolytic Agents; Logistic Models; Treatment Outcome; Thrombolytic Therapy
PubMed: 36515241
DOI: 10.1161/JAHA.122.026903 -
Postgraduate Medical Journal May 2003Diuretic drugs are used almost universally in patients with congestive heart failure, most frequently the potent loop diuretics. Despite their unproven effect on... (Review)
Review
Diuretic drugs are used almost universally in patients with congestive heart failure, most frequently the potent loop diuretics. Despite their unproven effect on survival, their indisputable efficacy in relieving congestive symptoms makes them first line therapy for most patients. In the treatment of more advanced stages of heart failure diuretics may fail to control salt and water retention despite the use of appropriate doses. Diuretic resistance may be caused by decreased renal function and reduced and delayed peak concentrations of loop diuretics in the tubular fluid, but it can also be observed in the absence of these pharmacokinetic abnormalities. When the effect of a short acting diuretic has worn off, postdiuretic salt retention will occur during the rest of the day. Chronic treatment with a loop diuretic results in compensatory hypertrophy of epithelial cells downstream from the thick ascending limb and consequently its diuretic effect will be blunted. Strategies to overcome diuretic resistance include restriction of sodium intake, changes in dose, changes in timing, and combination diuretic therapy.
Topics: Diuretics; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance; Heart Failure; Humans; Infusions, Intravenous; Injections; Treatment Refusal
PubMed: 12782772
DOI: 10.1136/pmj.79.931.268 -
Polish Archives of Internal Medicine Dec 2023Decongestion is a therapeutic target in acute heart failure (AHF). Acetazolamide is a diuretic that decreases proximal tubular sodium reabsorption, and may also reverse... (Randomized Controlled Trial)
Randomized Controlled Trial
Diuretic, natriuretic, and chloride-regaining effects of oral acetazolamide as an add-on therapy for acute heart failure with volume overload: a single-center, prospective, randomized study.
INTRODUCTION
Decongestion is a therapeutic target in acute heart failure (AHF). Acetazolamide is a diuretic that decreases proximal tubular sodium reabsorption, and may also reverse hypochloremia Objectives: We assessed the decongestive, natriuretic, and chloride‑regaining effects as well as the renal safety profile of oral acetazolamide (250 mg) used as an add‑on therapy in patients with AHF.
PATIENTS AND METHODS
This prospective, randomized study was conducted at the Institute of Heart Diseases in Wrocław, Poland. It involved patients with AHF who were randomly assigned to receive either 250 mg of oral acetazolamide or standard care, and who underwent clinical and laboratory follow‑up for 3 consecutive days since the beginning of the treatment and at discharge.
RESULTS
The study population comprised 61 patients (71% men), of whom 31 (51%) were included in the acetazolamide group. The mean (SD) age of the patients was 68 (13) years. In comparison with the controls, the acetazolamide group demonstrated significantly higher cumulative diuresis after 48 and 72 hours since treatment implementation, negative fluid balance, weight loss after 48 hours of treatment, weight loss throughout the hospitalization, natriuresis, and serum chloride concentration. In terms of the renal safety profile, no increase in the creatinine concentration and urinary renal biomarker levels was noted.
CONCLUSIONS
Oral acetazolamide seems to be a valuable add‑on therapy that helps achieve comprehensive decongestion in patients with AHF.
Topics: Male; Humans; Aged; Female; Diuretics; Acetazolamide; Chlorides; Prospective Studies; Heart Failure; Weight Loss
PubMed: 37415505
DOI: 10.20452/pamw.16526 -
Minerva Anestesiologica May 2009In an acute care setting, diuretics are often prescribed to maintain or increase urine output in patients presenting with acute kidney injury (AKI). The rationale behind... (Review)
Review
BACKGROUND
In an acute care setting, diuretics are often prescribed to maintain or increase urine output in patients presenting with acute kidney injury (AKI). The rationale behind giving diuretics is that they may protect the kidney from ischemic injury by maintaining a nonoliguric state. There have been many studies both supporting and criticizing diuretic use in AKI for improving overall patient outcomes.
METHODS
A systematic review of the literature was conducted to evaluate the role of diuretics including osmotics, loop diuretics, and nesiritide in modifying AKI.
RESULTS
There was no evidence to suggest that the use of loop diuretics in AKI reduces mortality, the need for dialysis, the number of dialysis sessions, or length of Intensive Care Unit/hospital stay or that it increases the recovery of renal function. There is no benefit for the use of mannitol as an osmotic diuretic over hydration in rhabdomyolysis. In contrast, mannitol was found to cause more harm and to induce nephropathy. Nesiritide did not improve renal function in patients with decompensated heart failure and mild chronic renal insufficiency. Nesiritide may be effective in the prevention of AKI when applied in lower doses for a prolonged period of time in patients with mild to moderate renal insufficiency.
CONCLUSIONS
Diuretics have been shown to be ineffective in the prevention of AKI or for improving outcomes once AKI occurs. At best, diuretics can help decrease symptoms of pulmonary edema secondary to volume overload.
Topics: Acute Kidney Injury; Animals; Cohort Studies; Combined Modality Therapy; Contraindications; Critical Care; Disease Models, Animal; Diuretics; Diuretics, Osmotic; Dopamine; Fluid Therapy; Furosemide; Humans; Length of Stay; Mannitol; Meta-Analysis as Topic; Natriuretic Peptide, Brain; Pulmonary Edema; Randomized Controlled Trials as Topic; Renal Dialysis; Rhabdomyolysis; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome
PubMed: 18636060
DOI: No ID Found -
Revista Portuguesa de Cardiologia Nov 2018Heart failure is a disease with high direct and indirect costs. Current treatment includes drugs that alter disease progression and drugs that to improve symptoms. Loop... (Review)
Review
Heart failure is a disease with high direct and indirect costs. Current treatment includes drugs that alter disease progression and drugs that to improve symptoms. Loop diuretics are the cornerstone of congestion relief for acute management, as well as for chronic stabilization. In heart failure patients, maximal diuretic response is reduced by many individual factors. Diuretic resistance is defined as failure to achieve effective congestion relief despite appropriate or escalating diuretic doses. Its causes include impaired delivery of the diuretic to its luminal site of action, neurohormonal activation, tubular compensatory adaptation and drug interactions. Several strategies can be employed to aid decongestion of patients with impaired diuretic response. These include salt restriction, a higher effective single dose or higher dose frequency of loop diuretics, continuous infusion of diuretics and/or sequential nephron blockade through a synergistic combination of two or more diuretics from different classes. Ultrafiltration has also been found to be another effective and safe therapeutic option and should be considered in patients with refractory diuretic resistance. Overall, there is a lack of high-quality clinical data to guide the choice of treatment strategy and therapy should be tailored on a case-by-case basis.
Topics: Aged; Aged, 80 and over; Diuretics; Drug Resistance; Heart Failure; Humans; Middle Aged
PubMed: 30470451
DOI: 10.1016/j.repc.2018.03.014 -
Nature Reviews. Nephrology Feb 2015Conventional diuretics such as furosemide and thiazides target salt transporters in kidney tubules, but urea transporters (UTs) have emerged as alternative targets. UTs... (Review)
Review
Conventional diuretics such as furosemide and thiazides target salt transporters in kidney tubules, but urea transporters (UTs) have emerged as alternative targets. UTs are a family of transmembrane channels expressed in a variety of mammalian tissues, in particular the kidney. UT knockout mice and humans with UT mutations exhibit reduced maximal urinary osmolality, demonstrating that UTs are necessary for the concentration of urine. Small-molecule screening has identified potent and selective inhibitors of UT-A, the UT protein expressed in renal tubule epithelial cells, and UT-B, the UT protein expressed in vasa recta endothelial cells. Data from UT knockout mice and from rodents administered UT inhibitors support the diuretic action of UT inhibition. The kidney-specific expression of UT-A1, together with high selectivity of the small-molecule inhibitors, means that off-target effects of such small-molecule drugs should be minimal. This Review summarizes the structure, expression and function of UTs, and looks at the evidence supporting the validity of UTs as targets for the development of salt-sparing diuretics with a unique mechanism of action. UT-targeted inhibitors may be useful alone or in combination with conventional diuretics for therapy of various oedemas and hyponatraemias, potentially including those refractory to treatment with current diuretics.
Topics: Animals; Diuretics; Humans; Membrane Transport Proteins; Urea Transporters
PubMed: 25488859
DOI: 10.1038/nrneph.2014.219 -
Therapeutic Advances in Cardiovascular... Oct 2013The objective of this review is to evaluate the role of fixed-dose triple-combination therapy for the management of hypertension. An assessment of clinical trials showed... (Comparative Study)
Comparative Study Review
The objective of this review is to evaluate the role of fixed-dose triple-combination therapy for the management of hypertension. An assessment of clinical trials showed that half the patients with hypertension have uncontrolled blood pressure (BP), with underlying factors including therapeutic inertia and poor patient adherence. Many patients will require three antihypertensive agents to achieve BP goals, and current guidelines recommend combining drugs with complementary mechanisms of action. Three single-pill triple-combination treatments are available and each includes an agent affecting the renin-angiotensin-aldosterone pathway (either a direct renin inhibitor or an angiotensin II receptor blocker) in combination with a calcium channel blocker and diuretic. These triple-combination therapies consistently demonstrated significantly greater BP reduction relative to the component dual combinations, with BP reductions documented across a range of patient populations. Triple-combination treatments were well tolerated in all clinical trials reviewed. The use of single-pill, triple-combination antihypertensive therapy has been shown to be an effective, well-tolerated, and convenient treatment strategy that can help patients achieve BP control.
Topics: Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Clinical Trials as Topic; Diuretics; Drug Combinations; Humans; Hypertension; Practice Guidelines as Topic; Renin-Angiotensin System; Treatment Outcome
PubMed: 23945906
DOI: 10.1177/1753944713498638 -
JACC. Heart Failure Aug 2017
Topics: Diuretics; Heart Failure; Humans; Length of Stay; Patient Readmission; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 28774402
DOI: 10.1016/j.jchf.2017.05.007 -
Current Cardiology Reviews 2016Heart failure (HF) has a high incidence and prevalence in the USA and worldwide. It is a very common cause of significant morbidity and mortality with serious cost... (Review)
Review
Heart failure (HF) has a high incidence and prevalence in the USA and worldwide. It is a very common cause of significant morbidity and mortality with serious cost implications on the US health sector. The primary focus of this review is to synthesize an effective comprehensive care plan for patients in acute decompensated heart failure (ADHF) based on the most current evidence available. It begins with a brief overview of the pathophysiology, clinical presentation and evaluation of patients in ADHF. It then reviews management goals and treatment guidelines, with emphasis on challenges presented by diuretic resistance and worsening renal function (WRF). It provides information on recognition of advanced HF even during acute presentation, estimation of prognosis and proactive identification of patients that will benefit from mechanical cardiac devices, transplantation and palliative care/hospice. In addition, it presents strategies to address the problem of readmissions, which is an ominous prognostic factor with enormous economic burden.
Topics: Acute Disease; Diuretics; Drug Resistance; Heart Failure; Humans; Incidence; Prognosis
PubMed: 26926295
DOI: 10.2174/1573403x12666160301120030 -
Circulation Nov 2023Hospitalization is recognized as a sentinel event in the disease trajectory of patients with heart failure (HF), but not all patients experiencing clinical...
BACKGROUND
Hospitalization is recognized as a sentinel event in the disease trajectory of patients with heart failure (HF), but not all patients experiencing clinical decompensation are ultimately hospitalized. Outpatient intensification of diuretics is common in response to symptoms of worsening HF, yet its prognostic and clinical relevance, specifically for patients with HF with mildly reduced or preserved ejection fraction, is uncertain.
METHODS
In this prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we assessed the association between various nonfatal worsening HF events (those requiring hospitalization, urgent outpatient visits requiring intravenous HF therapies, and outpatient oral diuretic intensification) and rates of subsequent mortality. We further examined the treatment effect of dapagliflozin on an expanded composite end point of cardiovascular death, HF hospitalization, urgent HF visit, or outpatient oral diuretic intensification.
RESULTS
In DELIVER, 4532 (72%) patients experienced no worsening HF event, whereas 789 (13%) had outpatient oral diuretic intensification, 86 (1%) required an urgent HF visit, 585 (9%) had an HF hospitalization, and 271 (4%) died of cardiovascular causes as a first presentation. Patients with a first presentation manifesting as outpatient oral diuretic intensification experienced rates of subsequent mortality that were higher (10 [8-12] per 100 patient-years) than those without a worsening HF event (4 [3-4] per 100 patient-years) but similar to rates of subsequent death after an urgent HF visit (10 [6-18] per 100 patient-years). Patients with an HF hospitalization as a first presentation of worsening HF had the highest rates of subsequent death (35 [31-40] per 100 patient-years). The addition of outpatient diuretic intensification to the adjudicated DELIVER primary end point (cardiovascular death, HF hospitalization, or urgent HF visit) increased the overall number of patients experiencing an event from 1122 to 1731 (a 54% increase). Dapagliflozin reduced the need for outpatient diuretic intensification alone (hazard ratio, 0.72 [95% CI, 0.64-0.82]) and when analyzed as a part of an expanded composite end point of worsening HF or cardiovascular death (hazard ratio, 0.76 [95% CI, 0.69-0.84]).
CONCLUSIONS
In patients with HF with mildly reduced or preserved ejection fraction, worsening HF requiring oral diuretic intensification in ambulatory care was frequent, adversely prognostic, and significantly reduced by dapagliflozin.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03619213.
Topics: Humans; Stroke Volume; Outpatients; Heart Failure; Benzhydryl Compounds; Heart Failure, Diastolic; Diuretics; Ventricular Function, Left
PubMed: 37632455
DOI: 10.1161/CIRCULATIONAHA.123.066506