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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 -
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 -
Journal of the American College of... Aug 2020
Topics: Aged; Diuretics; Furosemide; Heart Failure; Humans; Prescriptions; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 32762902
DOI: 10.1016/j.jacc.2020.06.044 -
European Journal of Emergency Medicine... Apr 2023Acute heart failure (AHF) is one of the main causes of unplanned hospitalization in patients >65 years of age and is associated with adverse outcomes in this...
BACKGROUND AND IMPORTANCE
Acute heart failure (AHF) is one of the main causes of unplanned hospitalization in patients >65 years of age and is associated with adverse outcomes in this population. Observational studies suggest that intravenous diuretic therapy given in the first hour of presentation for AHF was associated with favorable outcomes.
OBJECTIVES
To study the short-term prognostic associations of the timing of intravenous diuretic therapy in patients admitted to the emergency department (ED) for acute AHF.
DESIGN, SETTINGS AND PARTICIPANTS
Patients treated in the ED with intravenous diuretics were selected from the Estratificação de Doentes com InsuFIciência Cardíaca Aguda (EDIFICA) registry, a prospective study including AHF hospitalized patients. Early and non-early furosemide treatment groups were considered using the 1-h cutoff: door-to-furosemide ≤1 h and >1 h.
OUTCOMES MEASURE AND ANALYSIS
Primary outcomes were a composite of heart failure re-hospitalizations or cardiovascular death at 30- and 90-days.
MAIN RESULTS
Four-hundred ninety-three patients were included in the analysis. The median (interquartile range) door-to-furosemide time was 85 (41-220) min, and 210 (43%) patients had diuretics in the first hour. Patients in the ≤1 h group had higher evaluation priority according to the Manchester Triage System, presented more often with acute pulmonary edema, warm-wet clinical profile, higher blood pressure, and signs of left-side heart failure, while >1 h group had higher Get With the Guidelines-heart failure risk score, more frequent signs of right-side heart failure, higher circulating B-type natriuretic peptides and lower albumin. Door-to-furosemide ≤ 1 h was independently associated with lower 30-day heart failure hospitalizations and composite of heart failure hospitalizations or cardiovascular death (adjusted analysis Heart Failure Hospitalizations: odds ratios (OR) 3.65; 95% confidence interval (CI), 1.22-10.9; P = 0.020; heart failure hospitalizations or cardiovascular death: OR 3.15; 95% CI, 1.49-6.64; P < 0.001). These independent associations lost significance at 90 days.
CONCLUSION
Door-to-furosemide ≤1 h was associated with a lower short-term risk of heart failure hospitalizations or cardiovascular death in AHF patients. Our findings add to the existing evidence that early identification and intravenous diuretic therapy of AHF patients may improve outcomes.
Topics: Humans; Acute Disease; Diuretics; Furosemide; Heart Failure; Prospective Studies
PubMed: 36735452
DOI: 10.1097/MEJ.0000000000001006 -
The Journal of Pharmacology and... Aug 20228-Aminoguanine and 8-aminoguanosine (via metabolism to 8-aminoguanine) are endogenous 8-aminopurines that induce diuresis, natriuresis, and glucosuria by inhibiting...
8-Aminoguanine and 8-aminoguanosine (via metabolism to 8-aminoguanine) are endogenous 8-aminopurines that induce diuresis, natriuresis, and glucosuria by inhibiting purine nucleoside phosphorylase (PNPase); moreover, both 8-aminopurines cause antikaliuresis by other mechanisms. Because 8-aminoinosine and 8-aminohypoxanthine are structurally similar to 8-aminoguanosine and 8-aminoguanine, respectively, we sought to define their renal excretory effects. First, we compared the ability of 8-aminoguanine, 8-aminohypoxanthine, and 8-aminoinosine to inhibit recombinant PNPase. These compounds inhibited PNPase with a potency order of 8-aminoguanine > 8-aminohypoxanthine = 8-aminoinosine. Additional studies showed that 8-aminoinosine is a competitive substrate that is metabolized to a competitive PNPase inhibitor, namely 8-aminohypoxanthine. Administration of each 8-aminopurine (33.5 µmol/kg) reduced the guanine-to-guanosine and hypoxanthine-to-inosine ratios in urine, a finding confirming their ability to inhibit PNPase in vivo. All three 8-aminopurines induced diuresis, natriuresis, and glucosuria; however, the glucosuric effects of 8-aminohypoxanthine and 8-aminoinosine were less pronounced than those of 8-aminoguanine. Neither 8-aminohypoxanthine nor 8-aminoinosine altered potassium excretion, whereas 8-aminoguanine caused antikaliuresis. In vivo administration of 8-aminoinosine increased 8-aminohypoxanthine excretion, indicating that 8-aminohypoxanthine mediates, in part, the effects of 8-aminoinosine. Finally, 8-aminohypoxanthine was metabolized to 8-aminoxanthine by xanthine oxidase. Using ultraperformance liquid chromatography-tandem mass spectrometry, we identified 8-aminoinosine as an endogenous 8-aminopurine. In conclusion, 8-aminopurines have useful pharmacological profiles. To induce diuresis, natriuresis, glucosuria, and antikaliuresis, 8-aminoguanine (or its prodrug 8-aminoguanosine) would be preferred. If only diuresis and natriuresis, without marked glucosuria or antikaliuresis, is desired, 8-aminohypoxanthine or 8-aminoinosine might be useful. Finally, here we report the in vivo existence of another pharmacologically active 8-aminopurine, namely 8-aminoinosine. SIGNIFICANCE STATEMENT: Here, we report that a family of 8-aminopurines affects renal excretory function: effects that may be useful for treating multiple diseases including hypertension, heart failure, and chronic kidney disease. For diuresis and natriuresis accompanied by glucosuria and antikaliuresis, 8-aminoguanine (or its prodrug 8-aminoguanosine) would be useful; if only diuresis and natriuresis is called for, 8-aminohypoxanthine or 8-aminoinosine would be useful. Previously, we identified 8-aminoguanine and 8-aminoguanosine as endogenous 8-aminopurines; here, we extend the family of endogenous 8-aminopurines to include 8-aminoinosine.
Topics: Humans; Diuresis; Diuretics; Glycosuria; Natriuresis; Prodrugs; Purine-Nucleoside Phosphorylase
PubMed: 35609923
DOI: 10.1124/jpet.122.001221 -
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 -
Jornal Brasileiro de Nefrologia 2021Thiazide and thiazide-like diuretics are widely used for the management of hypercalciuria among stone-forming patients. Although the effects of different thiazides...
Thiazide and thiazide-like diuretics are widely used for the management of hypercalciuria among stone-forming patients. Although the effects of different thiazides should be relatively similar in terms of prevention of stone recurrence, their potency and side effects may differ. However, there is scarce data concerning the metabolic and bone effects of these agents among recurrent nephrolithiasis patients with hypercalciuria. The aim of this update article was to compare our experience in the use of thiazide and thiazide- like diuretics with that of the current literature, concerning their anticalciuric properties and consequent reduction of recurrent stone formation. Their impact on bone mass and potential side effects were also discussed.
Topics: Diuretics; Humans; Kidney Calculi; Nephrolithiasis; Recurrence; Thiazides
PubMed: 33179717
DOI: 10.1590/2175-8239-JBN-2019-0148 -
World Journal of Gastroenterology Jul 2019Since the 1970s, non-selective beta-blockers (NSBB) have been used to prevent variceal upper bleeding in advanced cirrhotic patients. However, several recent studies... (Review)
Review
Since the 1970s, non-selective beta-blockers (NSBB) have been used to prevent variceal upper bleeding in advanced cirrhotic patients. However, several recent studies have raised the doubt about the benefit of NSBB in end-stage cirrhotic patients. In fact, they suggested a detrimental effect in these patients that even reduced survival. All of these studies have been assembled to compose the "window therapy hypothesis", in which NSBB would have traditional indication to be initiated to prevent variceal upper bleeding; however, treatment should be stopped (or not be initiated) in patients with end-stage cirrhosis. NSBB would reduce the cardiac reserve of these patients, worsening systemic perfusion and prognosis. However, it should be emphasized that these studies present important bias issues, and their results also suggested that diuretic treatment may also be behind the effects observed. In this opinion review, we changed the point of view from NSBB to diuretic treatment, based on a physiopathogenic approach of circulatory parameters of cirrhotic patients studied, and based on diuretic effect in blood pressure lowering and in other hypervolemic disease, as heart failure. We suggest a "diuretic window hypothesis", composed by an open window in hypervolemic phase, an attention window when patient present in a normal plasma volume phase, and a closed window during the plasma hypovolemic phase.
Topics: Adrenergic beta-Antagonists; Diuretics; End Stage Liver Disease; Esophageal and Gastric Varices; Evidence-Based Medicine; Gastroenterology; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Prognosis; Survival Analysis; Treatment Outcome
PubMed: 31341355
DOI: 10.3748/wjg.v25.i26.3283 -
Journal of Clinical Hypertension... Sep 2022There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood... (Review)
Review
There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic.
Topics: Adrenergic alpha-Antagonists; Aged; Aldosterone; Antihypertensive Agents; Diuretics; Doxazosin; Humans; Hypertension; Renin
PubMed: 36196467
DOI: 10.1111/jch.14556 -
Revista Medica de Chile Apr 2022Persistent congestion following an episode of acute heart failure is associated with higher morbidity and mortality. Monitoring diuretic therapy is essential to guide...
Persistent congestion following an episode of acute heart failure is associated with higher morbidity and mortality. Monitoring diuretic therapy is essential to guide effective decongestion before patient discharge. Unfortunately, there are no markers which can predict on their own, the exact point in which euvolemia is achieved. Cardiothoracic and extra thoracic ultrasound are other tools to consider when evaluating hemodynamic and interstitial components of congestion. However, the question of which and how many parameters must be used for this purpose, is still unanswered.
Topics: Acute Disease; Diuretics; Heart Failure; Hemodynamics; Humans; Patient Discharge; Treatment Outcome
PubMed: 36155759
DOI: 10.4067/S0034-98872022000400493