Torsemide in Edema Associated with Chronic Kidney Disease.

Torsemide is a loop diuretic used to manage edema associated with chronic kidney disease (CKD) and acute kidney injury (AKI). It acts by inhibiting sodium and chloride ions reabsorption in the ascending limb of the loop of Henle, thereby increasing urine output and reducing fluid accumulation. Compared to other diuretics, torsemide has an extended duration of action, higher bioavailability, and its elimination route is primarily through the hepatic route, making it effective in patients with CKD and AKI. Clinical studies indicate that torsemide can improve symptoms of fluid overload and potentially enhance renal function.

Torsemide in the Management of Pulmonary Edema.

Pulmonary edema, either cardiogenic or noncardiogenic, is caused by fluid accumulation in the alveolar spaces. Cardiogenic pulmonary edema (CPE), one of the causes of congestive heart failure (CHF), is treated with loop diuretics. Torsemide and furosemide were found to be useful in the treatment of CHF-associated pulmonary edema due to their ability to lower pulmonary capillary pressure and left ventricular end-diastolic pressure, respectively. Pharmacological features of torsemide, such as greater bioavailability, higher absorption rate, and efficacy, make it a better alternative for treating pulmonary edema than the regularly used loop diuretic, furosemide. Torsemide administered intravenously was found to be both efficacious and well tolerated in CPE. However, more research is needed to determine its usefulness in non-CPE.

Torsemide in Edema Associated with Hepatic Impairment.

Hepatic edema is caused by decreased hepatic protein synthesis, a consequence of decompensated liver cirrhosis. Fluid accumulation occurs when there is an increase in hydrostatic pressure in the hepatic sinusoids and splanchnic capillaries, as well as low albumin. The first-line treatment for cirrhosis-related ascites is an aldosterone antagonist (spironolactone); however, in severe and recurring ascites, a combination of aldosterone antagonists and loop diuretics (torsemide, furosemide, and bumetanide) is preferable. Torsemide outperformed furosemide in terms of natriuretic and diuretic effects at an equivalent dose. Pharmacological features of torsemide, such as lesser hypokalemia effect, longer duration of action, higher bioavailability, and extended half-life, make it a better alternative than furosemide. In clinical studies, it is considered a safer and more acceptable choice with fewer complications.

Torsemide in the Management of Essential Hypertension.

Torsemide, a loop diuretic, is increasingly recognized for its role in managing essential hypertension. Its mechanism of action involves inhibiting the reabsorption of sodium and chloride ions in the ascending loop of Henle in the kidneys. By doing so, torsemide promotes diuresis, which refers to increased urine production, and subsequently lowers blood pressure. Studies have shown that torsemide is comparably effective to other antihypertensive agents in lowering blood pressure, with the added benefit of potentially improving renal function. However, while torsemide shows promise in hypertensive management, further research is necessary to fully understand its long-term effects and to establish optimal dosing strategies. Future research should focus on clarifying its role in long-term blood pressure control and refining its use in clinical practice to maximize efficacy and minimize adverse effects.

Torsemide versus Furosemide in the Treatment of Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. / Torsemida em Comparação com Furosemida no Tratamento da Insuficiência Cardíaca: Uma Revisão Sistemática e Metanálise de Ensaios Clínicos Randomizados.

Furosemide is the most used diuretic for volume overload symptoms in patients with heart failure (HF). Recent data suggested that torsemide may be superior to furosemide in this setting. However, whether this translates into better clinical outcomes in this population remains unclear. To assess whether torsemide is superior to furosemide in the setting of HF. We performed a systematic review and meta-analysis of RCTs comparing the efficacy of torsemide versus furosemide in patients with HF. PubMed, Embase, and Web of Science were searched for eligible trials. Outcomes of interest were all-cause hospitalizations, hospitalizations for HF (HHF), hospitalizations for all cardiovascular causes, all-cause mortality, and NYHA class improvement. Echocardiographic parameters were also assessed. We applied a random-effects model to calculate risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) and a 0.05 level of significance. 12 RCTs were included, comprising 4,115 patients. Torsemide significantly reduced HHF (RR 0.60; 95% CI, 0.43-0.83; p=0.002; I2=0%), hospitalization for cardiovascular causes (RR 0.72; 95% CI, 0.60-0.88; p=0.0009; I2=0%), and improved LVEF (MD 4.51%; 95% CI, 2.94 to 6.07; p<0.0001; I2=0%) compared with furosemide. There was no significant difference in all-cause hospitalizations (RR 0.93; 95% CI, 0.86-1.00; p=0.04; I2=0%), all-cause mortality (RR 0.98; 95% CI, 0.87-1.10; p=0.73; I2=0%), NYHA class improvement (RR 1.25; 95% CI, 0.92-1.68; p=0.15; I2=0%), or NYHA class change (MD -0.04; 95% CI, -0.24 to 0.16; p=0.70; I2=15%) between groups. Torsemide significantly reduced hospitalizations for HF and cardiovascular causes, also improving LVEF.

A furosemida é o diurético mais utilizado para o tratamento de sintomas de sobrecarga de volume em pacientes com insuficiência cardíaca. Dados recentes sugerem que a torsemida pode ser superior à furosemida neste contexto. No entanto, ainda não é claro se isso se traduz em melhores resultados clínicos nesta população. Avaliar se a torsemida é superior à furosemida no contexto da insuficiência cardíaca. Realizamos uma revisão sistemática e metanálise de estudos clínicos randomizados (ECRs) comparando a eficácia da torsemida em comparação com a furosemida em pacientes com insuficiência cardíaca. PubMed, Embase e Web of Science foram as bases de dados pesquisadas em busca de estudos elegíveis. Os desfechos de interesse foram internações por todas as causas, internações por insuficiência cardíaca (IIC), internações por todas as causas cardiovasculares, mortalidade por todas as causas, e melhoria de classe da NYHA. Parâmetros ecocardiográficos também foram avaliados. Foi aplicado um modelo de efeitos aleatórios para calcular as razões de risco (RR) e as diferenças médias (DM) com intervalos de confiança (IC) de 95% e nível de significância de 0,05. Foram incluídos 12 ECRs, envolvendo 4.115 pacientes. A torsemida reduziu significativamente a IIC (RR de 0,60; IC de 95%, 0,43-0,83; p=0,002; I2=0%), internação por causas cardiovasculares (RR de 0,72; IC de 95%, 0,60-0,88; p=0,0009; I2=0%), e melhora da fração de ejeção do ventrículo esquerdo (FEVE) (DM de 4,51%; IC de 95%, 2,94 a 6,07; p<0,0001; I2=0%) em comparação com a furosemida. Não houve diferença significativa no número de internações por todas as causas (RR de 0,93; IC de 95%, 0,86-1,00; p=0,04; I2=0%), mortalidade por todas as causas (RR de 0,98; IC de 95%, 0,87-1,10; p=0,73; I2=0%), melhora da classe NYHA (RR de 1,25; IC de 95%, 0,92-1,68; p=0,15; I2=0%), ou mudança de classe NYHA (DM de -0,04; IC de 95%, -0,24 a 0,16; p=0,70; I2=15%) entre os grupos. A torsemida reduziu significativamente as internações por insuficiência cardíaca e causas cardiovasculares, melhorando também a FEVE.

On-treatment analysis of torsemide versus furosemide for patients hospitalized for heart failure: A post-hoc analysis of TRANSFORM-HF.

AIM: The TRANSFORM-HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non-adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on-treatment analysis inclusive of all randomized patients except those confirmed non-adherent to study diuretic. METHODS AND RESULTS: TRANSFORM-HF was an open-label, pragmatic randomized trial of 2859 patients hospitalized for HF from June 2018 through March 2022. Patients were randomized to a loop diuretic strategy of torsemide versus furosemide with investigator-selected dosage. This post-hoc on-treatment analysis included all patients alive with either known or unknown diuretic status, and excluded patients confirmed to be non-adherent to study diuretic. This modified on-treatment definition was applied separately at time of hospital discharge and 30-day follow-up. All-cause mortality and hospitalization outcomes were assessed over 12 months. Overall, 2570 (89.9%) and 2374 (83.0%) patients were included in on-treatment analyses at discharge and 30-day follow-up, respectively. There was no significant difference in all-cause mortality between torsemide and furosemide in patients on-treatment at discharge (17.5% vs. 17.8%; hazard ratio [HR] 1.01 [95% confidence interval [CI] 0.83-1.22], p = 0.96) and at 30-day follow-up (14.5% vs. 15.0%; HR 1.02 [95% CI 0.81-1.27], p = 0.90). All-cause mortality or all-cause hospitalization was similar between torsemide and furosemide in patients who were on-treatment at discharge (58.3% vs. 61.3%; HR 0.92 [95% CI 0.82-1.03]) and 30-day follow-up (60.9% vs. 64.4%; HR 0.93 [95% CI 0.82-1.05]). In patients who were on-treatment at 30-day follow-up, there were 677 total hospitalizations in the torsemide group and 686 total hospitalizations in the furosemide group (rate ratio 0.99 [95% CI 0.86-1.14], p = 0.87). CONCLUSIONS: In TRANSFORM-HF, a post-hoc on-treatment analysis did not meaningfully differ from the original trial results. Among those deemed compliant with the assigned diuretic, there remained no significant difference in mortality or hospitalization after HF hospitalization with a strategy of torsemide versus furosemide. CLINICAL TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT03296813.

Impact of baseline kidney dysfunction on oral diuretic efficacy following hospitalization for heart failure - insights from TRANSFORM-HF.

AIM: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half-life, but direct supportive evidence is lacking. METHODS AND RESULTS: The TRANSFORM-HF trial randomized patients hospitalized for HF to a long-term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post-hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30-<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30-<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all-cause mortality and all-cause (re)-hospitalizations, both when assessing eGFR categorically or continuously (p-value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ-CSS (p-value for interaction all >0.052) when assessing eGFR categorically or continuously. CONCLUSION: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient-reported outcomes between torsemide and furosemide, irrespective of renal function.

Clinical effect of torsemide in a horse with congestive heart failure and atrial fibrillation.

In this case report, a high dose of torsemide (6mg/kg, every 12 hours for 3 days followed by 12mg/kg, every 12 hours for 4 days) was administered orally to a horse with congestive heart failure (CHF) and atrial fibrillation. Blood samples for measurement of plasma torsemide concentrations were obtained one hour after each drug administration. Pharmacodynamic effects of oral torsemide were evaluated by daily physical examination, electrocardiography, and serum biochemistry. The horse tolerated administration of torsemide. A decrease in ventral oedema and venous congestion was subjectively noted at day 7. Torsemide plasma concentration markedly increased at day 5 (peak concentration of 15.41 µg/mL). Evidence of an increase in renal markers was observed throughout the study period. Electrolyte measurements revealed mild hyponatremia and hypochloremia, and moderate hypokalaemia. No electrocardiographic changes related to torsemide administration were observed. After seven days of treatment, the horse was euthanised due to his disease stage and poor prognosis. Results indicate that torsemide was absorbed after oral administration and was well tolerated in this horse. Furthermore, clinical improvement in this single case indicates that torsemide might be utilized as an oral alternative to furosemide in the management of equine patients in CHF. The high doses of torsemide used in this case report should be reserved for cases without clinical response to lower doses and with close monitoring of electrolytes and renal function parameters. Further investigation of torsemide clinical efficacy and safety in horses with CHF with a larger cohort and prolonged administration is warranted.

Torsemide vs Furosemide Among Patients With New-Onset vs Worsening Chronic Heart Failure: A Substudy of the TRANSFORM-HF Randomized Clinical Trial.

Importance: Differences in clinical profiles, outcomes, and diuretic treatment effects may exist between patients with de novo heart failure (HF) and worsening chronic HF (WHF). Objectives: To compare clinical characteristics and treatment outcomes of torsemide vs furosemide in patients hospitalized with de novo HF vs WHF. Design, Setting, and Participants: All patients with a documented ejection fraction who were randomized in the Torsemide Comparison With Furosemide for Management of Heart Failure (TRANSFORM-HF) trial, conducted from June 18 through March 2022, were included in this post hoc analysis. Study data were analyzed March to May 2023. Exposure: Patients were categorized by HF type and further divided by loop diuretic strategy. Main Outcomes and Measures: End points included all-cause mortality and hospitalization outcomes over 12 months, as well as change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results: Among 2858 patients (mean [SD] age, 64.5 [14.0] years; 1803 male [63.1%]), 838 patients (29.3%) had de novo HF, and 2020 patients (70.7%) had WHF. Patients with de novo HF were younger (mean [SD] age, 60.6 [14.5] years vs 66.1 [13.5] years), had a higher glomerular filtration rate (mean [SD], 68.6 [24.9] vs 57.0 [24.0]), lower levels of natriuretic peptides (median [IQR], brain-type natriuretic peptide, 855.0 [423.0-1555.0] pg/mL vs 1022.0 [500.0-1927.0] pg/mL), and tended to be discharged on lower doses of loop diuretic (mean [SD], 50.3 [46.2] mg vs 63.8 [52.4] mg). De novo HF was associated with lower all-cause mortality at 12 months (de novo, 65 of 838 [9.1%] vs WHF, 408 of 2020 [25.4%]; adjusted hazard ratio [aHR], 0.50; 95% CI, 0.38-0.66; P < .001). Similarly, lower all-cause first rehospitalization at 12 months and greater improvement from baseline in KCCQ-CSS at 12 months were noted among patients with de novo HF (median [IQR]: de novo, 29.94 [27.35-32.54] vs WHF, 23.68 [21.62-25.74]; adjusted estimated difference in means: 6.26; 95% CI, 3.72-8.81; P < .001). There was no significant difference in mortality with torsemide vs furosemide in either de novo (No. of events [rate per 100 patient-years]: torsemide, 27 [7.4%] vs furosemide, 38 [10.9%]; aHR, 0.70; 95% CI, 0.40-1.14; P = .15) or WHF (torsemide 212 [26.8%] vs furosemide, 196 [24.0%]; aHR, 1.08; 95% CI, 0.89-1.32; P = .42; P for interaction = .10), In addition, no significant differences in hospitalizations, first all-cause hospitalization, or total hospitalizations at 12 months were noted with a strategy of torsemide vs furosemide in either de novo HF or WHF. Conclusions and Relevance: Among patients discharged after hospitalization for HF, de novo HF was associated with better clinical and patient-reported outcomes when compared with WHF. Regardless of HF type, there was no significant difference between torsemide and furosemide with respect to 12-month clinical or patient-reported outcomes.

Comparative Effect of Loop Diuretic Prescription on Mortality and Heart Failure Readmission.

Loop diuretics are a standard pharmacologic therapy in heart failure (HF) management. Although furosemide is most frequently used, torsemide and bumetanide are increasingly prescribed in clinical practice, possibly because of superior bioavailability. Few real-world comparative effectiveness studies have examined outcomes across all 3 loop diuretics. The study goal was to compare the effects of loop diuretic prescribing at HF hospitalization discharge on mortality and HF readmission. We identified patients in Medicare claims data initiating furosemide, torsemide, or bumetanide after an index HF hospitalization from 2007 to 2017. We estimated 6-month risks of all-cause mortality and a composite outcome (HF readmission or all-cause mortality) using inverse probability of treatment weighting to adjust for relevant confounders. We identified 62,632 furosemide, 1,720 torsemide, and 2,389 bumetanide initiators. The 6-month adjusted all-cause mortality risk was lowest for torsemide (13.2%), followed by furosemide (14.5%) and bumetanide (15.6%). The 6-month composite outcome risk was 21.4% for torsemide, 24.7% for furosemide, and 24.9% for bumetanide. Compared with furosemide, the 6-month all-cause mortality risk was 1.3% (95% confidence interval [CI]: -3.7, 1.0) lower for torsemide and 1.0% (95% CI: -1.2, 3.2) higher for bumetanide, and the 6-month composite outcome risk was 3.3% (95% CI: -6.3, -0.3) lower for torsemide and 0.2% (95% CI: -2.5, 2.9) higher for bumetanide. In conclusion, the findings suggested that the first prescribed loop diuretic following HF hospitalization is associated with clinically important differences in morbidity in older patients receiving torsemide, bumetanide, or furosemide. These differences were consistent for the effect of all-cause mortality alone, but were not statistically significant.

Effect of Furosemide Versus Torsemide on Hospitalizations and Mortality in Patients With Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

Loop diuretics are essential in the treatment of patients with heart failure (HF) who develop congestion. Furosemide is the most commonly used diuretic; however, some randomized controlled trials (RCTs) have shown varying results associated with torsemide and furosemide in terms of hospitalizations and mortality. We performed an updated meta-analysis of currently available RCTs comparing furosemide and torsemide to see if there is any difference in clinical outcomes in patients treated with these loop diuretics. PubMed, MEDLINE, Cochrane, and Embase databases were searched for RCTs comparing the outcomes in patients with HF treated with furosemide versus torsemide. The primary end points included all-cause mortality, all-cause hospitalizations, cardiovascular-related hospitalizations, and HF-related hospitalizations. A random-effects meta-analysis was performed to estimate the risk ratio (RR) with a 95% confidence interval (CI). A total of 10 RCTs with 4,127 patients (2,088 in the furosemide group and 2,039 in the torsemide group) were included in this analysis. A total of 56% of the patients were men and the mean age was 68 years. No significant difference was noted in all-cause mortality between the furosemide and torsemide groups (RR 1.02, 95% CI 0.91 to 1.15, p = 0.70); however, patients treated with furosemide compared with torsemide had higher risks of cardiovascular hospitalizations (RR 1.36, 95% CI 1.13 to 1.65, p = 0.001), HF-related hospitalizations (RR 1.65, 95% CI 1.21 to 2.24, p = 0.001), and all-cause hospitalizations (RR 1.06, 95% CI 1.01 to 1.11, p = 0.02). In conclusion, patients with HF treated with torsemide have a reduced risk of hospitalizations compared with those treated with furosemide, without any difference in mortality. These data indicate that torsemide may be a better choice to treat patients with HF.

Clinical Outcomes With Furosemide Versus Torsemide in Patients With Heart Failure: An Updated Systematic Review and Meta-Analysis.

Despite potential advantages of torsemide over furosemide, <10% of the patients with heart failure (HF) are on torsemide in clinical practice. Prior studies comparing furosemide to torsemide in patients with HF have shown conflicting findings, regarding hospitalizations and mortality. We aimed to pool all the studies conducted to date and provide the most updated and comprehensive evidence, regarding the effect of furosemide vs torsemide in reducing mortality and hospitalizations in patients with HF. We conducted a comprehensive literature search of the PubMed/Medline, Cochrane Library and Scopus from inception till June 2023, for randomized and nonrandomized studies comparing furosemide to torsemide in adult patients (>18 years) with acute or chronic HF. Data about all-cause mortality, HF-related hospitalizations and all-cause hospitalizations was extracted, pooled, and analyzed. Forest plots were created based on the random effects model. A total of 17 studies (n = 11,996 patients) were included in our analysis with a median follow-up time of 8 months. Our pooled analysis demonstrated no difference in all-cause mortality between furosemide and torsemide groups in HF patients (OR = 0.98, 95% CI: 0.75-1.29, P = 0.89). However, torsemide was associated with a significantly lesser incidence of HF-related hospitalizations (OR = 0.73, 95% CI: 0.54-0.99, P = 0.04), and all-cause hospitalizations (OR = 0.84, 95% CI: 0.73-0.98, P = 0.03), as compared to furosemide. Torsemide significantly reduces HF-related and all-cause hospitalizations as compared to furosemide, with no difference in mortality. We recommend transitioning from furosemide to torsemide in HF patients who are not attaining symptomatic control.

Effect of Torsemide Versus Furosemide on Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.

BACKGROUND: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. METHODS: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0-100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0-6; score ≥3 supporting evaluation for depression) over 12 months. RESULTS: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27-60) in the torsemide group and 40 (24-59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, -2.26 to 2.37]; P=0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P=0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, -0.64 to 3.36]; P=0.18) and 6-month follow-up (adjusted mean difference, -0.37 [95% CI, -2.52 to 1.78]; P=0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. CONCLUSIONS: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03296813.

Torsemide increases arsenic concentrations by inhibition of multidrug resistance protein 4 in arsenic trioxide treated acute promyelocytic leukemia patients.

Torsemide is commonly used to relieve edema during the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). We explored the effect of torsemide on the plasma concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMAV) and dimethyarsinic acid (DMAV) in APL patients treated with ATO and clarified its molecular mechanism in rats and cells. The study included 146 APL patients treated with ATO. 60（41.1 %) of these 146 patients were co-administered with torsemide. The treatment of torsemide increased plasma concentrations of iAs (P < 0.05) and DMAV (P < 0.05) in APL patients. The single co-administration of ATO and torsemide in rats significantly increased the plasma concentrations and AUC(0-t) of iAs (P < 0.05) and MMAV (P < 0.05), decreased the urinary excretion rates and the urine concentrations of iAs (P < 0.05) and DMAV (P < 0.05), and enhanced iAs (P < 0.05) and MMAV (P < 0.05) concentrations in the kidneys of rats. In addition, torsemide decreased the expression of multidrug resistance protein 4 (MRP4) in rat kidneys after 7 days of continuous co-administration (P < 0.05). We also treated MRP4-overexpressing HEK293T cells with ATO and different concentrations of torsemide. Torsemide markedly increased the concentrations of iAs, MMAV and DMAV by inhibiting MRP4 compared with ATO alone (P < 0.05). In conclusion, torsemide increased the plasma concentrations of arsenic metabolites in APL patients treated with ATO by inhibiting the transporter MRP4 in a dose-dependent manner.

Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.

Importance: Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. Objective: To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure. Design, Setting, and Participants: TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022. Interventions: Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage. Main Outcomes and Measures: The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide. Results: TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction. Conclusions and Relevance: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Trial Registration: ClinicalTrials.gov Identifier: NCT03296813.