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Comparative effectiveness of torasemide versus furosemide in symptomatic therapy in heart failure patients: Preliminary results from the randomized TORNADO trial.

ABSTRACT:

Background

Recent reports suggest that torasemide might be more beneficial than furosemide in patients with symptomatic heart failure (HF). The aim was to compare the effects of torasemide and furosemide on clinical outcomes in HF patients.

Methods

This study pilot consisted of data from the ongoing multicenter, randomized, unblinded endpoint phase IV TORNADO (NCT01942109) study. HF patients in New York Heart Association (NYHA) II-IV class with a stable dose of furosemide were randomized to treatment with equipotential dose of torasemide (4:1) or continuation of unchanged dose of furosemide. On enrollment and control visit (3 months after enrollment) clinical examination, 6-minute walk test (6MWT) and assessment of fluid retention by ZOE Fluid Status Monitor were performed. The primary endpoint was a composite of improvement of NYHA class, improvement of at least 50 m during 6MWT and decrease in fluid retention of at least 0.5 W after 3-months follow-up.

Results

The study group included 40 patients (median age 66 years; 77.5% male). During follow-up 7 patients were hospitalized for HF worsening (3 in torasemide and 4 in furosemide-treated patients). The primary endpoint reached 15 (94%) and 14 (58%) patients on torasemide and furosemide, respectively (p = 0.03).

Conclusions

In HF patients treated with torasemide fluid overload and symptoms improved more than in the furosemide group. This positive effect occurred already within 3-month observation.

SUBMITTER: Balsam P

PROVIDER: S-EPMC8083045 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundApproximately 50% of heart failure patients are readmitted to hospital within 6 months, owing to deterioration of their condition. Thus, symptomatic treatment of heart failure requires significant improvement. The aim of this study is to compare the effects of torasemide and furosemide on biochemical parameters of haemodynamic and neurohormonal compensation, myocardial remodelling, clinical outcomes and quality of life in patients with chronic heart failure.MethodsThis is a multicentre, randomized, open, blinded endpoint phase-IV trial. The study includes 120 heart failure patients in NYHA (New York Heart Association) functional class II-IV, treated with optimal heart failure therapy, with indications for use of loop diuretics. At enrolment, patients are stable, with a fixed dose of loop diuretics. Patients are randomized to treatment with furosemide or torasemide (randomization 1:1). After randomization, the current fixed dose of furosemide is continued or is replaced by an equipotential dose of torasemide (4:1). The study consists of two control visits (3 and 6 months after enrolment) with minimal follow-up of 6 months. Assessment involves clinical examination, Quality of Life Questionnaire, laboratory tests, echocardiography, electrocardiography, 24 h Holter-electrocardiography monitoring, 6 -min walk test and assessment of fluid retention. Any need for dose adjustment is assessed during the observation. The primary objective is to compare the effects of torasemide and furosemide on clinical and biochemical parameters of haemodynamic and neurohormonal compensation and myocardial remodelling. Secondary objectives include monitoring of: changes in signs and symptoms of heart failure, NYHA functional class, quality of life, dosage changes, rate of readmissions and mortality.DiscussionDespite decades of the diuretic's history, knowledge about diuretic therapy is still unsatisfactory. The most widely used diuretic, furosemide, has a stormy pharmacokinetics and pharmacodynamics, and is associated with a high risk of mortality and hospitalization for worsening heart failure. Reports are very encouraging and suggest beneficial effects of torasemide. Hence, there is a need for further studies of the overall effect of torasemide, compared with furosemide. This can translate into improved quality of life and better prognosis of patients with heart failure.Trial registrationClinicalTrials.gov, NCT01942109 . Registered on 24 August 2013.

Project description:PurposeDiuretics are the primary treatment for the management of chronic heart failure (HF) symptoms and for the improvement of acute HF symptoms. The rate of delivery to the site of action has been suggested to affect diuretic pharmacodynamics. The main objective of this clinical trial was to explore whether a prolonged release tablet formulation of torasemide (torasemide-PR) was more natriuretically efficient in patients with chronic HF compared to immediate-release furosemide (furosemide-IR) after a single-dose administration. Moreover, the pharmacokinetics of torasemide-PR, furosemide-IR, and torasemide-IR were assessed in chronic HF patients as well as urine pharmacodynamics.MethodsRandomized, open-label, blinded-endpoint, crossover, and single-dose Phase I clinical trial with three experimental periods. Torasemide-PR and furosemide-IR were administered as a single dose in a crossover fashion for the first two periods, and torasemide-IR 10 mg was administered for the third period. Blood and urine samples were collected at fixed timepoints. The primary endpoint was the natriuretic efficiency after administration of torasemide-PR and furosemide-IR, defined as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours.ResultsTen patients were included and nine completed the study. Here, we present the results from nine patients. Torasemide-PR was more natriuretically efficient than furosemide-IR (0.096 ± 0.03 mmol/μg vs 0.015 ± 0.0007 mmol/μg; P < 0.0001). Mictional urgency was lower and more delayed with torasemide-PR than with furosemide-IR.ConclusionIn a study with a limited sample size, our results suggest that 10 mg of torasemide-PR is more natriuretically efficient than 40 mg of furosemide-IR after single-dose administration in patients with chronic HF over a 24-hour collection period. Further studies are necessary to evaluate potential pharmacodynamic differences between torasemide formulations and to assess its impact on clinical therapeutics.

Project description:ObjectivesThis paper aims to compare the effectiveness of sacubitril-valsartan and angiotensin-converting enzyme inhibitor (ACE)/angiotensin receptor blocker (ARB) in systolic heart failure (HF).BackgroundSacubitril-valsartan reduced risks of death and hospitalization for HF versus enalapril in ambulatory patients with HF and reduced ejection fraction in the PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor with Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) trial. However, the comparative effectiveness of sacubitril-valsartan and ACE/ARB in patients treated in routine clinical practice is unclear.MethodsWe identified patients with systolic HF in a U.S. administrative claims database treated with sacubitril-valsartan or ACE/ARB from July 1, 2015, to February 2, 2018. One-to-one propensity score matching was used to balance patients on 29 clinical variables. Cox models were used to compare outcomes between treatment groups.ResultsA total of 7,893 matched pairs were included; mean (SD) follow-up was 6.3 (5.4) months. Sacubitril-valsartan was associated with lower risks of all-cause mortality or all-cause hospitalization (hazard ratio [HR]: 0.86, 95% confidence interval (CI): 0.81 to 0.91; p < 0.001), all-cause mortality (HR: 0.80, 95% CI: 0.66 to 0.97; p = 0.027), and all-cause hospitalization (HR: 0.86, 95% CI: 0.80 to 0.91; p < 0.001), but not HF hospitalization (HR: 1.07, 95% CI: 0.96 to 1.19; p = 0.26). A lower risk of the primary outcome with sacubitril-valsartan was observed in white patients (HR: 0.83, 95% CI: 0.76 to 0.90) but not black patients (21% of population, HR: 1.00, 95% CI: 0.88 to 1.15; interaction p = 0.032). No statistically significant differences in treatment response by sex or age were observed.ConclusionsSacubitril-valsartan was associated with lower risks of death and hospitalization compared with ACE/ARB in a heterogeneous cohort of patients with systolic HF. However, our finding that outcomes with sacubitril-valsartan and ACE/ARBs were similar in black patients warrants further evaluation.

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