Subcutaneous Furosemide in Heart Failure: Pharmacokinetic Characteristics of a Newly Buffered Solution.
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SUBMITTER: Sica DA
PROVIDER: S-EPMC6059009 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
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Subcutaneous Furosemide in Heart Failure: Pharmacokinetic Characteristics of a Newly Buffered Solution.
Sica Domenic A DA Muntendam Pieter P Myers Rene L RL Ter Maaten Jozine M JM Sale Mark E ME de Boer Rudolf A RA Pitt Bertram B
JACC. Basic to translational science 20180207 1
Parenteral diuretics form the cornerstone of decongestion in heart failure. However, parenteral therapy routinely requires emergency room or inpatient care. A novel buffered furosemide formulation with neutral pH was developed to offer "hospital-strength" diuresis for outpatient use, including self-administration at home. Subcutaneous infusion using a biphasic delivery profile resulted in complete bioavailability (99.65%) and equivalent diuresis when compared with intravenous administration. Sub ...[more]
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Project description:We aimed to evaluate the efficacy (short-term changes in surrogates of decongestion) and safety following the ambulatory administration of subcutaneous furosemide (SCF) in patients with WHF. Fifty-five ambulatory patients were treated with SCF administered by an elastomeric pump for at least 72 h. Surrogates of congestion were assessed at baseline, 72 h, and 30 days. Spot urinary sodium (uNa+) was assessed at baseline, 24-48-72 h, and 30 days. The median (IQI) of NT-proBNP and uNa+ at baseline was 5218 pg/mL (2856-10878) and 68±3 mmol/L, respectively. Following administration of SCF (median dose of 100 mg/daily), we found a sustained increase in uNa+ during the first 72 h of treatment compared to baseline, paralleled with evidence of decongestion at 72 h, and 30 days. No significant safety concerns were observed. SCF was an effective and safe diuretic strategy for outpatient congestion management. Non-formulated subcutaneous furosemide in patients with WHF. Efficacy and safety.
| S-EPMC9213343 | biostudies-literature
Project description:AimsThis study aims to establish the feasibility, safety, and efficacy of outpatient intravenous (IV) diuretic treatment for the management of decompensated heart failure (HF) for patients enrolled in the HeartFailure@Home service.Methods and resultsWe retrospectively analysed the clinical episodes of decompensated HF for patients enrolled in the HeartFailure@Home service, managed by ambulatory IV diuretic treatment either at home or on a day-case unit. A control group consisting of HF patients admitted to hospital for IV diuretics (standard-of-care) was also evaluated. In total, 203 episodes of decompensated HF (n = 154 patients) were evaluated. One hundred and fourteen episodes in 79 patients were managed exclusively by the ambulatory IV diuretic service-78 (68.4%) on a day-case unit and 36 (31.6%) domiciliary; 84.1% of patient episodes under the HF@Home service were successfully managed entirely in an out-patient setting without hospitalization. Eleven patients required admission in order to administer higher doses of IV diuretics than could be provided in the ambulatory setting. During follow-up, there were 20 (17.5%) 30 day re-admissions with HF or death in the ambulatory IV group and 29 (32.6%) in the standard-of-care arm (P = 0.02). There was no difference in 30 day HF readmissions between the two groups (14.9% ambulatory vs. 13.5% inpatients, P = 0.8), but 30 day mortality was significantly lower in the ambulatory group (3.5% vs. 21.3% inpatients, P < 0.001).ConclusionsOutpatient ambulatory management of decompensated HF with IV diuretics given either on a day case unit or in a domiciliary setting is feasible, safe, and effective in selected patients with decompensated HF. This should be explored further as a model in delivering HF services in the outpatient setting during COVID-19.
| S-EPMC8497198 | biostudies-literature
Project description:BackgroundHyponatremia, a marker of disease severity and prognosis, has been associated with various clinical factors and drug use, especially diuretics.MethodsThis observational prospective cohort study enrolled patients hospitalized at the University Hospital Center Split because of heart failure (HF). We investigated the association of clinical variables and cardiovascular drugs, including furosemide, hydrochlorothiazide, spironolactone, and their doses, with the presence of hyponatremia at admission.ResultsOf the 565 included patients, 32.4% were hyponatremic, 62.6% were males, and the mean age was 73.1 ± 10.6 years. In the univariate analysis, hyponatremic patients were more often current smokers (p = 0.01), alcohol consumers (p = 0.01), receiving spironolactone (p = 0.004) or combination of furosemide and spironolactone (p = 0.003). Patients who received 50 and 100 mg of spironolactone, compared to those receiving 25 mg (p < 0.0001), as well as patients who received 250 to 500 mg of furosemide compared to ≤240 mg (p = 0.001), were significantly more often hyponatremic. In the multivariate analysis, when diuretic doses were accounted for, furosemide doses of 250 to 500 mg (p = 0.009), spironolactone doses of 50 to 100 mg (p = 0.0003), increasing age (p = 0.03), diabetes mellitus (p = 0.02) and alcohol consumption (p = 0.04) were independently associated with hyponatremia.ConclusionHigh doses of furosemide and spironolactone, or concomitant use of these diuretics, seem to be an important cause of hyponatremia in HF patients, particularly in combination with advanced age, diabetes and alcohol consumption. Diuretic dose reduction may help avoid hyponatremia and improve clinical status and prognosis in such patients.
| S-EPMC7397681 | biostudies-literature
Project description:AimsHeart failure (HF) and atrial fibrillation (AF) may coexist and influence each other. However, characteristics, anticoagulant treatment, and outcomes of contemporary AF patients with concurrent HF are ill-defined. This study analyses characteristics, treatment, and 2 year outcomes in newly diagnosed Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) patients with vs. without HF.Methods and resultsGARFIELD-AF is the world's largest observational AF patient study. At enrolment, 11 758 of 52 072 patients (22.6%) had HF; 76.3% were New York Heart Association class II-III. Patients with HF had comparable demographics, blood pressure, and heart rate but more likely had permanent (15.6% vs. 11.9%) or persistent AF (18.9% vs. 13.8%), acute coronary syndromes (16.7% vs. 8.9%), vascular disease (40.8% vs. 20.2%), and moderate-to-severe chronic kidney disease (14.6% vs. 9.0%) than those without. Anticoagulant prescription was similar between the two groups. At 2 year follow-up, patients with HF showed a greater risk of all-cause mortality [hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.91-2.21; P < 0.0001], cardiovascular mortality (HR, 2.91; 95% CI, 2.58-3.29; P < 0.0001), acute coronary syndromes (HR, 1.25; 95% CI, 1.02-1.52; P = 0.03), and stroke/systemic embolism (HR, 1.24; 95% CI, 1.07-1.43; P = 0.0044). Major bleeding rate was comparable (adjusted HR, 1.00; 95% CI, 0.84-1.18; P = 0.968). Among patients without HF at baseline, incidence of new HF was low [0.69 (95% CI, 0.63-0.75) per 100 person-years], whereas propensity to develop worsening HF was higher in those with HF [1.62 (95% CI, 1.45-1.80) per 100 person-years].ConclusionsPatients with AF and HF have a high risk of all-cause and cardiovascular mortality and stroke/systemic embolism and may develop worsening HF.
| S-EPMC8006724 | biostudies-literature
Project description:AimsWe sought to compare the effects of furosemide + hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers.Methods and resultsWe enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plus HSS compared with controls treated with furosemide alone showed a comparable degree of reduction in the serum levels of interleukin (IL)-6, soluble suppression of tumorigenicity 2 (sST2), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the 'between-group' analysis. Nevertheless, patients treated with high-dose furosemide + HSS showed significantly higher absolute delta values of IL-6 (2.3 ± 1.2 vs. 1.7 ± 0.9, P < 0.0005, and 2.0 ± 0.8 vs. 1.85 ± 1.1, P = 0.034), sST2 (41.2 ± 8.6 vs. 27.9 ± 7.6, P < 0.0005, and 37.1 ± 6.6 vs. 28.4 ± 6.7, P < 0.0005), high-sensitivity troponin T (0.03 ± 0.02 vs. 0.02 ± 0.01, P = 0.001, and 0.03 ± 0.02 vs. 0.02 ± 0.01, P = 0.009), NT-proBNP (7237 ± 7931 vs. 3244 ± 4159, P < 0.005, and 5381 ± 4829 vs. 4466 ± 4332, P = 0.004), and galectin-3 (15.7 ± 3.2 ng/mL vs. 11.68 ± 1.9 ng/mL, P < 0.0005, and 16.7 ± 3.9 ng/mL vs. 11.8 ± 2.4 ng/mL, P < 0.0005) than patients treated with furosemide alone. After acute saline load, patients treated with i.v. furosemide + HSS in comparison with subjects treated with furosemide alone showed a significantly lower increase in the serum concentrations of IL-6 (-0.26 ± 0.42 pg/mL vs. -1.43 ± 0.86 pg/mL, P < 0.0005), high-sensitivity troponin T (0 vs. -0.02 ± 0.02 ng/mL, P < 0.0005), sST2 (-8.5 ± 5.9 ng/mL vs. -14.6 ± 6.2 ng/mL, P < 0.0005), galectin-3 (-2.1 ± 1.5 ng/mL vs. -7.1 ± 3.6 ng/mL, P < 0.0005), and NT-proBNP (77 ± 1373 vs. -1706 ± 2259 pg/mL, P < 0.0005).ConclusionsOur findings concerning a comparable degree of reduction in the serum levels of three cardinal biomarkers indicate that a reduction in serum heart failure markers is not linked to the higher degree of congestion relief with a more rapid achievement of a clinical compensation state. This issue may have possible benefits on clinical practice concerning its therapeutic effects over and beyond the simple amelioration of clinical congestion signs and symptoms. Nevertheless, our findings of higher delta values after treatment with i.v. furosemide plus HSS indicate a possible higher efficacy by means of modulation of the stretching and fibrosis mechanisms.
| S-EPMC8497323 | biostudies-literature
Project description:AimThe authors assessed the comparative effectiveness of torsemide versus furosemide in the PROTECT trial.MethodsThe authors assessed the relationship between loop diuretic at discharge and death or cardiovascular/renal hospitalization within 30 days, and death through 150 days postdischarge using inverse probability weighting.ResultsOut of 1004 patients, 83.5% received furosemide and 16.5% torsemide. Torsemide patients had higher blood urea nitrogen, and more in-hospital worsening heart failure. Following adjustment, torsemide was associated with similar 30-day outcomes compared with furosemide (p = 0.93), but remained associated with increased 150-day death (hazard ratio: 2.26; 95% CI: 1.40-3.66; p < 0.001).ConclusionPatients treated with torsemide had features of greater disease severity, similar 30-day outcomes but increased 150-day mortality. Prospective randomized trials are needed to investigate the effect of torsemide versus furosemide.
| S-EPMC5558519 | biostudies-literature
Project description:AimsHyponatremia is associated with poorer outcomes and diuretic response in patients hospitalized for heart failure. This study compared a tolvaptan-based vs. furosemide-based diuretic regimen on short-term clinical responses in hyponatremic acute heart failure.Methods and resultsProspective, randomized, open-label, parallel-group, single-centre study comparing oral tolvaptan vs. continuous infusion furosemide. Thirty-three subjects requiring hospitalization for acute congestive heart failure, and a serum sodium < 135 mmol/L, were randomized to tolvaptan 30 mg orally daily or furosemide 5 mg/h intravenously for initial 24 h, after which treatments could be escalated. Median daily dose throughout was tolvaptan 30 mg and furosemide 120 mg, with four subjects in each group requiring dose escalation. Urine output and net fluid balance were not different between groups at 24 h or subsequent time points up to 96 h. Changes in estimated glomerular filtration rate were comparable. Cystatin C improved at 24 h with tolvaptan compared with furosemide (-6.4 ± 11.8 vs. 4.1 ± 17.2% change, P = 0.036), but the effect was transient. No significant between group differences were seen for NT-proBNP, plasma renin activity, or urinary neutrophil gelatinase-associated lipocalin:Cr. Serum sodium, as well as copeptin levels, increased with tolvaptan compared with furosemide.ConclusionsOral tolvaptan was associated with similar, but not superior, diuresis compared with intravenous furosemide for acute heart failure with concomitant hyponatremia.
| S-EPMC7373913 | biostudies-literature
Project description: Not available
| S-EPMC4467558 | biostudies-literature
Project description:AimAcute heart failure can be a life-threatening medical condition. Delaying administration of intravenous furosemide (time-to-diuretics) has been postulated to increase mortality, but prior reports have been inconclusive. We aimed to evaluate the association between time-to-diuretics and mortality in the international REPORT-HF registry.Methods and resultsWe assessed the association of time-to-diuretics within the first 24 h with in-hospital and 30-day post-discharge mortality in 15 078 patients from seven world regions in the REPORT-HF registry. We further tested for effect modification by baseline mortality risk (ADHERE risk score), left ventricular ejection fraction (LVEF) and region. The median time-to-diuretics was 67 (25th-75th percentiles 17-190) min. Women, patients with more signs and symptoms of heart failure, and patients from Eastern Europe or Southeast Asia had shorter time-to-diuretics. There was no significant association between time-to-diuretics and in-hospital mortality (p > 0.1). The 30-day mortality risk increased linearly with longer time-to-diuretics (administered between hospital arrival and 8 h post-hospital arrival) (p = 0.016). This increase was more significant in patients with a higher ADHERE risk score (pinteraction = 0.008), and not modified by LVEF or geographic region (pinteraction > 0.1 for both).ConclusionIn REPORT-HF, longer time-to-diuretics was not associated with higher in-hospital mortality. However, we did found an association with increased 30-day mortality, particularly in high-risk patients, and irrespective of LVEF or geographic region.Clinical trial registrationClinicalTrials.gov Identifier NCT02595814.
| S-EPMC10099670 | biostudies-literature
Project description:AimsThe outpatient diuretic dose is a marker of diuretic resistance and prognosis in chronic heart failure (HF). Still, the impact of the preadmission dose on diuretic efficiency (DE) and prognosis in acute HF is not fully known.Methods and resultsWe conducted an observational and prospective study. All patients admitted for acute HF treated with intravenous diuretic and at least one criterion of congestion on admission were evaluated. Decongestion [physical examination, hemoconcentration, N-terminal pro-brain natriuretic peptide (NT-proBNP) change, and lung ultrasound], DE (weight loss and urine output per unit of 40 mg furosemide), and urinary sodium were monitored on the fifth day of admission. DE was dichotomized into high-low based on the median value. A multivariate Cox regression analysis was conducted to find predictors of HF readmission or mortality. A total of 105 patients were included between July 2017 and July 2019. Mean age was 74.5 ± 12.0 years, 64.8% were male, 33.3% had de novo HF, and mean left ventricular ejection fraction was 46 ± 17%. Median follow-up was 26 [15-35] months. Low DE based on weight loss was associated with a higher previous dose of furosemide (odds ratio [OR] 1.01 [1.00-1.02]), thiazide treatment before admission (OR 9.37 [2.19-40.14]), and lower diastolic blood pressure (OR 0.95 [0.91-0.98]) in the multivariate regression model. Only previous dose of furosemide (OR 1.01 [1.00-1.02]) and haemoglobin at admission (OR 0.76 [0.58-0.99]) were associated with low DE based on urine output in the multivariate analysis. The correlation between the previous dose of furosemide and DE based on weight loss was poor (r = -0.12; P = 0.209) and with DE based on urine output was weak to moderate (r = -0.33; P < 0.001). Low DE based on weight loss and urine output was associated with lesser decongestion measured by NT-proBNP (P = 0.011; P = 0.007), hemoconcentration (P = 0.006; P = 0.044), and lung ultrasound (P = 0.034; P = 0.029), but not by physical examination (P = 0.506; P = 0.560). Survival and event-free survival in acute decompensated HF (ADHF) were lower than in de novo HF; a preadmission dose of furosemide > 80 mg in ADHF identified patients with particularly poor prognosis (log-rank < 0.001). In ADHF, the preadmission dose of furosemide (hazard ratio [HR] 1.34 [1.08-1.67] per 40 mg) and NT-proBNP at admission (HR 1.03 [1.01-1.06] per 1000 pg/mL) were independently associated with mortality or HF readmission in the multivariate Cox regression analysis.ConclusionsThe outpatient dose of furosemide before acute HF admission predicts DE and must be taken into account when deciding on the initial diuretic dose. In ADHF, the outpatient dose of furosemide can predict long-term prognosis better than DE during hospitalization.
| S-EPMC8788037 | biostudies-literature