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JAMA Jan 2023Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. (Randomized Controlled Trial)
Randomized Controlled 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.
Topics: Humans; Female; Middle Aged; Aged; Male; Furosemide; Torsemide; Patient Discharge; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Heart Failure; Hospitalization
PubMed: 36648467
DOI: 10.1001/jama.2022.23924 -
The American Journal of Cardiology Jan 2020Although torsemide's oral bioavailability and half-life theoretically render it a more efficient diuretic than furosemide, the clinical outcomes of torsemide compared... (Meta-Analysis)
Meta-Analysis Review
Although torsemide's oral bioavailability and half-life theoretically render it a more efficient diuretic than furosemide, the clinical outcomes of torsemide compared with furosemide remain unclear. We performed a systematic review and meta-analysis, including all published studies that compared torsemide and furosemide use in heart failure patients from January 1996 through August 2019. Nineteen studies (9 randomized control trials [RCTs] and 10 observational studies) with a total of 19,280 patients were included. During a mean follow-up duration of 15 months, torsemide was associated with a numerically lower risk of hospitalization due to heart failure (10.6% vs 18.4%; odds ratio [OR] 0.72, 95% confidence interval [CI] [0.51, 1.03], p = 0.07, I = 18%; number needed to treat [NNT] = 23) compared with furosemide. Torsemide was associated with statistically significant more improvement in functional status from New York Heart Association (NYHA) class III/IV to I/II (72.5% vs 58%; OR 2.32, 95% CI (1.32, 4.1), p = 0.004, I = 27%; NNT = 5) and lower risk of cardiac mortality (1.5% vs 4.4%; OR 0.37, 95% CI (0.20, 0.66), p <0.001, I = 0%, NNT = 40) compared with furosemide. However, there was no difference in all-cause mortality or medication side effects between the 2 groups. In conclusion, compared with furosemide, torsemide use was associated with significant more improvement in functional status and lower cardiac mortality; and numerically fewer hospitalizations in patients with heart failure.
Topics: Furosemide; Heart Failure; Humans; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Torsemide; Treatment Outcome
PubMed: 31699358
DOI: 10.1016/j.amjcard.2019.09.039 -
Journal of the American Pharmacists... 2019To compare the efficacy and safety of torsemide versus furosemide in patients with heart failure (HF). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the efficacy and safety of torsemide versus furosemide in patients with heart failure (HF).
DATA SOURCES
Medline, Cochrane Library, Web of Science, and Google Scholar database searches for relevant articles from 1946 to May 2018 were performed with the use of the key words torsemide and furosemide.
STUDY SELECTION
Studies were included if they met the following criteria: (1) cohort studies or randomized controlled trials of adult patients 18 years of age or older who received oral torsemide or furosemide for HF with reduced or preserved ejection fraction; and (2) studies that reported mortality rate, rehospitalization rate for HF or cardiovascular disease (CVD), or New York Heart Association (NYHA) functional class changes.
DATA EXTRACTION
Efficacy outcomes were mortality from any cause, rehospitalization for HF, rehospitalization for CVD, and NYHA functional class improvement. Safety outcome included hypokalemia.
RESULTS
In the 5 included studies, there was no significant difference in mortality between torsemide and furosemide (odds ratio [OR] 1.00, 95% CI 0.58-1.72; P = 0.99; I = 79%). There was no significant difference in rehospitalization rates for HF (OR 0.79, 95% CI 0.57-1.09; P = 0.15; I = 64%) or CVD (OR 0.83, 95% CI 0.62-1.12; P = 0.22; I = 40%) between torsemide- and furosemide-treated patients. The use of torsemide was associated with significant improvement in NYHA functional class compared with furosemide (OR 1.44, 95% CI 1.18-1.76; P = 0.0004; I = 0%).
CONCLUSION
Our meta-analysis showed that torsemide is associated with statistically significant improvement in NYHA functional class for patients with HF compared with furosemide. However, torsemide did not provide significant benefits in reducing mortality or rehospitalization rates for HF or CVD compared with furosemide. The authors suggest switching from furosemide to torsemide in patients with HF not achieving symptomatic control with the use of furosemide despite maximizing guideline-directed medical therapy and furosemide dosing.
Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Databases, Factual; Furosemide; Heart Failure; Hospitalization; Humans; Middle Aged; Mortality; New York; Patients; Randomized Controlled Trials as Topic; Torsemide; Treatment Outcome
PubMed: 30846351
DOI: 10.1016/j.japh.2019.01.014 -
Expert Review of Cardiovascular Therapy Jan 2022Torsemide is a loop diuretic that inhibits the Na+/K+/2Cl- cotransporter type 2 in the thick ascending loop of Henle, leading to increased excretion of urinary sodium... (Review)
Review
INTRODUCTION
Torsemide is a loop diuretic that inhibits the Na+/K+/2Cl- cotransporter type 2 in the thick ascending loop of Henle, leading to increased excretion of urinary sodium and chloride and associated diuresis. While furosemide remains the dominant diuretic utilized in current practice, increasing evidence supports potential advantages of torsemide in heart failure (HF) and/or renal disease.
AREAS COVERED
This narrative review covers the evidence for use of torsemide in HF and renal disease. Comparative effectiveness with regards to clinical outcomes is reviewed, as well as the ongoing multicenter trial, TRANSFORM-HF, comparing the effect of torsemide versus furosemide among patients with HF.
EXPERT OPINION
Compared with furosemide, torsemide has favorable pharmacodynamics/pharmacokinetics including higher bioavailability, longer duration of effect, minor renal excretion, decreased kaliuresis, and enhanced natriuresis/diuresis. These properties may be further supported by differential effects on RAAS regulation and fibrosis modulation as compared with other diuretics. The limited current body of evidence indicates that torsemide may be superior to furosemide with respect to improving HF functional status and reducing HF hospitalization, and there are mixed data regarding effect on reducing overall cardiovascular hospitalizations/mortality. Further, randomized data are necessary to definitively determine if torsemide can reduce risk of mortality and hospitalization among patients with HF.
Topics: Diuretics; Furosemide; Heart Failure; Humans; Multicenter Studies as Topic; Sodium Potassium Chloride Symporter Inhibitors; Torsemide
PubMed: 34936522
DOI: 10.1080/14779072.2022.2022474 -
Circulation Jul 2023Loop 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... (Randomized Controlled Trial)
Randomized Controlled 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]; =0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: =0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, -0.64 to 3.36]; =0.18) and 6-month follow-up (adjusted mean difference, -0.37 [95% CI, -2.52 to 1.78]; =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.
Topics: Humans; Furosemide; Torsemide; Sodium Potassium Chloride Symporter Inhibitors; Quality of Life; Heart Failure; Stroke Volume
PubMed: 37212600
DOI: 10.1161/CIRCULATIONAHA.123.064842 -
Current Problems in Cardiology Nov 2023Despite potential advantages of torsemide over furosemide, <10% of the patients with heart failure (HF) are on torsemide in clinical practice. Prior studies comparing... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Adult; Humans; Furosemide; Torsemide; Sodium Potassium Chloride Symporter Inhibitors; Heart Failure; Hospitalization
PubMed: 37453532
DOI: 10.1016/j.cpcardiol.2023.101927 -
The Annals of Pharmacotherapy Apr 1995To review the clinical pharmacology of torsemide and to compare it with currently available loop diuretics, particularly furosemide. (Comparative Study)
Comparative Study Review
OBJECTIVE
To review the clinical pharmacology of torsemide and to compare it with currently available loop diuretics, particularly furosemide.
DATA SOURCES
An English-language MEDLINE search, 1985 to October 1994, was used to identify pertinent literature, including review articles.
DATA EXTRACTION
Data from scientific literature were extracted, evaluated, and summarized for presentation. Pivotal and representative studies are discussed relating to the pharmacology, pharmacokinetics, and use of torsemide in patients with congestive heart failure, renal disease, hepatic disease, and hypertension.
DATA SYNTHESIS
Torsemide is a loop diuretic of the pyridine-sulfonylurea class. The bioavailability of torsemide is approximately 80%, with little first-pass metabolism, and torsemide can be given without regard to meals. The serum concentration reaches its peak within 1 hour after oral administration and diuresis lasts approximately 6-8 hours. Torsemide is eliminated both hepatically (80%) and renally (20%) as unchanged drug with an elimination half-life of about 3.5 hours. Because of the high bioavailability, oral and intravenous doses are therapeutically equivalent. Torsemide, and other loop diuretics such as furosemide, are indicated for the treatment of edema associated with congestive heart failure, renal disease, and hepatic disease. They also are indicated for the treatment of hypertension alone or in combination with other antihypertensive agents. Depending on the indication, the recommended initial adult dosage of torsemide is between 5 and 20 mg once daily orally or intravenously. Special dosage adjustments in the elderly are not necessary.
CONCLUSIONS
Torsemide is a loop diuretic similar to furosemide, with similar indications. Torsemide is characterized by good bioavailability and once-daily dosing and, compared with furosemide, provides generally equivalent therapeutic efficacy.
Topics: Clinical Trials as Topic; Diuretics; Drug Interactions; Furosemide; Heart Failure; Humans; Liver Cirrhosis; Renal Insufficiency; Sulfonamides; Torsemide
PubMed: 7633019
DOI: 10.1177/106002809502900411 -
Cureus Jul 2023Heart failure is associated with an increased frequency of hospitalization, reduced life span, and greater risk to public health, thus posing a challenge. In India,... (Review)
Review
Heart failure is associated with an increased frequency of hospitalization, reduced life span, and greater risk to public health, thus posing a challenge. In India, torsemide is one of the commonly used loop diuretics for decongestion in heart failure. However, this use of torsemide, including its dosing, and up/down titration, is based on practical experience. Loop diuretic therapy for heart failure patients poses several dilemmas due to the lack of robust evidence based on which treatment decisions can be made. To guide physicians on the optimal use of torsemide in heart failure patients with or without renal impairment, a panel of expert cardiologists and nephrologists from India convened to develop this expert opinion document for the use of torsemide. This expert opinion on torsemide will pave the way for optimal management with loop diuretic therapy in real-world heart failure patients.
PubMed: 37588313
DOI: 10.7759/cureus.41957