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Javier Diez - One of the best experts on this subject based on the ideXlab platform.

  • torafic study protocol Torasemide prolonged release versus furosemide in patients with chronic heart failure
    Expert Review of Cardiovascular Therapy, 2009
    Co-Authors: Javier Diez, Erik Cobo, Ester Fernandez
    Abstract:

    Loop diuretics, such as Torasemide and furosemide, are important agents in the treatment of chronic heart failure. Beneficial effects of Torasemide immediate-release formulation beyond diuresis have been documented as the ability of this compound to inhibit myocardial synthesis and deposition of collagen type I in patients with chronic heart failure. In addition, Torasemide-treated patients, but not furosemide-treated patients, showed decreased serum concentrations of the C-terminal propeptide of procollagen type I, a biochemical marker of myocardial fibrosis. The aim of the TORAFIC study is to test the efficacy of Torasemide prolonged-release formulation (PR) in reducing myocardial fibrosis in chronic heart failure in a large, randomized clinical trial. Methods: This prospective, Phase IV, randomized, blinded end point, active-controlled clinical trial will randomize 142 patients with chronic heart failure in New York Heart Association functional class II-IV to 8 months treatment with either Torasemide-PR (10-40 mg daily) or furosemide (40-160 mg daily). The primary objective is to test the hypothesis that Torasemide-PR is superior to furosemide in reducing myocardial fibrosis. The primary outcome measure is the difference in the change of serum propeptide of procollagen type I concentration from the initial to the final visit between both study groups. Secondary outcome measures include all efficacy variables related to heart failure (signs and symptoms, ECG, echocardiogram and serum levels of N-terminal brain natriuretic propeptide). Secondary safety variables are heart rate, blood pressure, laboratory data, adverse events, cardiovascular events (hospital admission, emergency department visits) and quality of life (Minnesota questionnaire). Discussion: This trial will test whether Torasemide- PR possesses antifibrotic properties, which may provide an additional benefit beyond diuresis in patients with chronic heart failure.

  • Torasemide in chronic heart failure: results of the TORIC study.
    European journal of heart failure, 2002
    Co-Authors: Juan Cosin, Javier Diez
    Abstract:

    Background Diuretics such as Torasemide are commonly used to treat chronic heart failure (CHF). Aims The objective of the Torasemide In Congestive Heart Failure (TORIC) Study was to investigate the safety, tolerability and efficacy of Torasemide in CHF patients compared to furosemide or other diuretics in an open-label, non-randomised, post-marketing surveillance trial. Methods The present analysis shows the findings of 1377 patients with New York Heart Association (NYHA) class II–III CHF who received diuretic therapy with Torasemide 10 mg/day orally (n-778) vs. patients who received furosemide 40 mg/day orally (n-527) or other diuretics (n-72) on top of their existing standard CHF therapy for 12 months. Besides safety and tolerability, efficacy was assessed by documentation of mortality, morbidity, functional class and serum potassium levels every 3 months. Results TORIC confirmed the safety and tolerability of Torasemide in CHF patients. Mortality was significantly lower in the Torasemide (n-17, 2.2%) than in the furosemide/other diuretics group (n-27, 4.5%) (P

  • Torasemide in chronic heart failure results of the toric study
    European Journal of Heart Failure, 2002
    Co-Authors: Juan Cosin, Javier Diez
    Abstract:

    Background Diuretics such as Torasemide are commonly used to treat chronic heart failure (CHF). Aims The objective of the Torasemide In Congestive Heart Failure (TORIC) Study was to investigate the safety, tolerability and efficacy of Torasemide in CHF patients compared to furosemide or other diuretics in an open-label, non-randomised, post-marketing surveillance trial. Methods The present analysis shows the findings of 1377 patients with New York Heart Association (NYHA) class II–III CHF who received diuretic therapy with Torasemide 10 mg/day orally (n-778) vs. patients who received furosemide 40 mg/day orally (n-527) or other diuretics (n-72) on top of their existing standard CHF therapy for 12 months. Besides safety and tolerability, efficacy was assessed by documentation of mortality, morbidity, functional class and serum potassium levels every 3 months. Results TORIC confirmed the safety and tolerability of Torasemide in CHF patients. Mortality was significantly lower in the Torasemide (n-17, 2.2%) than in the furosemide/other diuretics group (n-27, 4.5%) (P<0.05). Functional improvement as assessed by NYHA class was observed in more patients who received furosemide Torasemide (n-356, 45.8%) than those who received furosemide/other diuretics (n-223, 37.2%) (P-0.00017). At the end of the study abnormally low serum potassium levels were observed in fewer Torasemide (n-95, 12.9%) than furosemide/other diuretics patients (n-102, 17.9%) (P-0.013). Conclusion Torasemide is safe and well tolerated in CHF patients. Although not designed as a mortality study, TORIC suggests a lower mortality amongst CHF patients treated with Torasemide compared to furosemide/other diuretics. A functional improvement and a lower incidence of abnormal serum potassium levels were also observed in patients receiving Torasemide as compared to those receiving furosemide/other diuretics.

  • Torasemide inhibits angiotensin ii induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats
    Hypertension, 1999
    Co-Authors: Ana Fortuno, Paula Muniz, Susana Ravassa, Jose A Rodriguez, Ma Antonia Fortuno, Guillermo Zalba, Javier Diez
    Abstract:

    Abstract —Torasemide is a loop diuretic that is effective at low once-daily doses in the treatment of arterial hypertension. Because its antihypertensive mechanism of action may not be based entirely on the elimination of salt and water from the body, a vasodilator effect of this drug can be considered. In the present study, the ability of different concentrations of Torasemide to modify angiotensin II (Ang II)–induced vascular responses was examined, with the use of an organ bath system, in endothelium-denuded aortic rings from spontaneously hypertensive rats. Ang II–induced increases of intracellular free calcium concentration ([Ca2+]i) were also examined by image analysis in cultured vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats. A dose-response curve to Ang II was plotted for cumulative concentrations (from 10−9 to 10−6 mol/L) in endothelium-denuded aortic rings (pD2=7.5±0.3). Isometric contraction induced by a submaximal concentration of Ang II (10−7 mol/L) was reduced in a dose-dependent way by Torasemide (IC50=0.5±0.04 μmol/L). Incubation of VSMCs with different concentrations of Ang II (from 10−10 to 10−6 mol/L) resulted in a dose-dependent rise of [Ca2+]i (pD2=7.5±0.3). The stimulatory effect of [Ca2+]i induced by a submaximal concentration of Ang II (10−7 mol/L) was blocked by Torasemide (IC50=0.5±0.3 nmol/L). Our findings suggest that Torasemide blocks the vasoconstrictor action of Ang II in vitro. This action can be related to the ability of Torasemide to block the increase of [Ca2+]i induced by Ang II in VSMCs. It is proposed that these actions might be involved in the antihypertensive effect of Torasemide observed in vivo.

Rosa M. Antonijoan - One of the best experts on this subject based on the ideXlab platform.

  • randomized, open-label, blinded-endpoint, crossover, single-dose study to compare the pharmacodynamics of Torasemide-Pr 10 mg, Torasemide-ir 10 mg, and furosemide-ir 40 mg, in patients with chronic heart failure
    Drug design development and therapy, 2015
    Co-Authors: Maria Ballester, Eulalia Roig, Ignasi Gich, Montse Puntes, Joaquín Delgadillo, Benjamín Santos, Rosa M. Antonijoan
    Abstract:

    Diuretics 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.Randomized, 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.Ten 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.In 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.

Michael D Murray - One of the best experts on this subject based on the ideXlab platform.

  • healthcare costs of patients with heart failure treated with Torasemide or furosemide
    PharmacoEconomics, 2000
    Co-Authors: Kevin T Stroupe, Melissa M Forthofer, Craig D Brater, Michael D Murray
    Abstract:

    Objective: To compare the direct healthcare costs of patients with congestive heart failure (CHF) prescribed Torasemide (torsemide) or furosemide (frusemide).

  • Healthcare Costs of Patients with Heart Failure Treated with Torasemide or Furosemide
    PharmacoEconomics, 2000
    Co-Authors: Kevin T Stroupe, Melissa M Forthofer, D. Craig Brater, Michael D Murray
    Abstract:

    Objective: To compare the direct healthcare costs of patients with congestive heart failure (CHF) prescribed Torasemide (torsemide) or furosemide (frusemide). Design and setting: As part of a prospective, randomised, nonblind study, we assessed the effects of Torasemide and furosemide on readmission to hospital in 193 patients treated for CHF at a US urban public healthcare system. We also calculated total direct healthcare costs for the 2 drugs. The perspective of the analysis was that of the healthcare system. Healthcare charge and utilisation data, demographic information, and health status data were obtained from an electronic database containing data for all patients treated within the healthcare system. Patients and participants: Upon admission to the hospital, patients were eligible if they had evidence of left ventricular systolic dysfunction, were at least 18 years old, and were receiving furosemide. Intervention: Inpatients were randomised to either Torasemide or furosemide treatment for 1 year. Main outcomemeasures and results: Patients treated with Torasemide had fewer hospital admissions than those treated with furosemide [18 vs 34% for CHF (p = 0.013) and 38 vs 58% for any cardiovascular cause (p = 0.005)]. In the Torasemide group, expected annual hospital costs per patient were lower for CHF admissions (by $US1054; 1998 values) and for all cardiovascular admissions (by $US1545) than in the furosemide group. Because the annual acquisition cost of Torasemide was $US518 per patient higher than that of furosemide, the resulting net cost saving per patient was $US536 for CHF and $US1027 for all cardiovascular causes. Outpatient costs did not differ between treatment groups regardless of whether drug costs were considered. Total direct costs were $US2124 lower with Torasemide than with furosemide (not statistically significant). Conclusions: Owing largely to reduced readmission to the hospital, the cost of inpatient care for patients with CHF is significantly lower with Torasemide than with furosemide, despite the higher acquisition cost of Torasemide. Treatment with Torasemide resulted in a nonsignificant reduction in total direct costs (outpatient plus inpatient) compared with furosemide.

Valerie Chetboul - One of the best experts on this subject based on the ideXlab platform.

  • short term efficacy and safety of Torasemide and furosemide in 366 dogs with degenerative mitral valve disease the test study
    Journal of Veterinary Internal Medicine, 2017
    Co-Authors: Valerie Chetboul, J L Pouchelon, J Menard, J Blanc, Loic Desquilbet, Amandine M P Petit, Sandrine Rougier, Laurence Lucats
    Abstract:

    Background Furosemide is the only loop diuretic recommended by the ACVIM consensus guidelines for treatment of congestive heart failure (CHF) in dogs related to degenerative mitral valve disease (DMVD). Torasemide is another potent loop diuretic with a longer half-life and a higher bioavailability. Objectives (1) To demonstrate that Torasemide given once a day (q24h) is noninferior to furosemide given twice a day (q12h) for treating dogs with CHF; (2) and to compare the effect of the 2 drugs on the time to reach a composite cardiac endpoint “spontaneous cardiac death, euthanasia due to heart failure or CHF class worsening.” Animals A total of 366 dogs with CHF attributable to DMVD. Methods Analysis of 2 prospective randomized single-blinded reference-controlled trials was performed. Dogs orally received either Torasemide q24h (n = 180) or furosemide q12h (n = 186) in addition to standard CHF therapy over 3 months. The primary efficacy criterion was the percentage of dogs with treatment success assessed in each study. The time to reach the composite cardiac endpoint was used as secondary criterion in the overall population. Results Torasemide was noninferior to furosemide (PTorasemide − Pfurosemide = +7%; 95% CI [−8%; +22%] and PTorasemide − Pfurosemide = +1%; 95% CI [−12%; +14%], respectively, in Study 1 and Study 2). Torasemide (median dose = 0.24 mg/kg/d q24h; range = 0.10–0.69 mg/kg/d) was associated with a 2-fold reduction in the risk of reaching the composite cardiac endpoint (adjusted HR = 0.47; 95% CI = 0.27–0.82; P = 0.0077) as compared with furosemide (median dose = 1.39 mg/kg q12h; range = 0.70–6.30 mg/kg q12h). Conclusions and Clinical Importance Torasemide q24h is an effective oral diuretic in dogs with CHF.

Masahiro Watanabe - One of the best experts on this subject based on the ideXlab platform.

  • Diuretic and hypotensive actions of Torasemide in hypertensive models of rat
    Drug Development Research, 1992
    Co-Authors: Takeshi Uchida, K. Yamanaga, Yutaka Ohtaki, Hideaki Kido, Hiroshi Shinyama, Kazutaka Hayashi, Masahiro Watanabe
    Abstract:

    The diuretic and the antihypertensive actions of Torasemide were examined in renal and genetic hypertensive rats and compared to the effects of furosemide. Oral administration of Torasemide (1 and 3 mg/kg) elicited a dose-dependent increase in the excretion of urine and electrolytes and elevated the urinary Na/K ratio in both renal and genetic hypertensive rats. Torasemide and furosemide had a similar maximum diuretic effect in the normotensive Wistar rat and the spontaneously hypertensive rat (SHR). However, the diuretic activity of furosemide was weaker in the renal hypertensive rat (RHR). Torasemide showed approximately 30 times greater diuretic potency than furosemide. Torasemide and furosemide demonstrated hypotensive action in hypertensive rat models, but not in the normotensive Wistar rat. Especially in the RHR, Torasemide exhibited a more potent hypotensive action than furosemide. These results show that the diuretic and antihypertensive activities of Torasemide are effective in various rat models of hypertension, while the diuretic activity of furosemide is weak in certain hypertensive rat models. © 1992 Wiley-Liss, Inc.

  • Torasemide, but not frusemide, increases intracellular cAMP and cGMP content in the aorta of the renal hypertensive rat.
    The Journal of pharmacy and pharmacology, 1992
    Co-Authors: K. Yamanaga, Takeshi Uchida, Hideaki Kido, Kazutaka Hayashi, Masahiro Watanabe
    Abstract:

    — Repeated oral administration of the novel loop diuretic Torasemide (3 mg kg−1) and frusemide (30 mg kg−1) for 7 days, elicited a significant fall in the systolic blood pressure in the one-kidney, one-clip Goldblatt renal hypertensive rat (RHR). The hypotensive action was greater in the Torasemide group than in the frusemide group. Furthermore Torasemide increased intracellular cAMP and cGMP content in aorta of RHR. Frusemide caused no effect. It is hypothesized that the increase in adenosine- or guanosine-nucleotides is involved in the antihypertensive action of Torasemide, but not in that of frusemide.

  • Anti-aldosteronergic effect of Torasemide.
    European journal of pharmacology, 1991
    Co-Authors: Takeshi Uchida, K. Yamanaga, Masakuni Nishikawa, Yutaka Ohtaki, Hideaki Kido, Masahiro Watanabe
    Abstract:

    The diuretic actions of Torasemide and furosemide were studied in normotensive rats and in deoxycorticosterone acetate (DOCA)-saline-loaded hypertensive rats. Torasemide (0.3-3 mg/kg) and furosemide (3-30 mg/kg) had a dose-dependent and significant diuretic action in normotensive rats. Potassium retention was only observed in the case of Torasemide. Torasemide also had a dose-dependent and significant diuretic action in DOCA-saline-loaded hypertensive rats, whereas furosemide did not. Higher doses of Torasemide (10 mg/kg) and furosemide (100 mg/kg) increased both plasma renin activity and aldosterone concentration in normotensive rats in a similar manner. In vivo aldosterone receptor binding was determined to test the possible anti-aldosteronergic effect of Torasemide. Torasemide inhibited the binding of aldosterone to its receptor in the cytoplasmic fraction of rat kidney in a dose-dependent manner, while furosemide produced no effect. These results suggest strongly that an anti-aldosteronergic action of Torasemide contributes to producing less kaliuresis.

  • Diuretic profile of a novel loop diuretic Torasemide in rats and dogs.
    Drugs under experimental and clinical research, 1991
    Co-Authors: T. Uchida, Y Ohtaki, H Kido, Masahiro Watanabe
    Abstract:

    In the present study, the authors have examined the diuretic action of a novel loop diuretic Torasemide and compared it to those of other diuretics, employing normal rats and dogs. Oral administration of Torasemide elicited a dose-dependent increase in urine volume and electrolyte excretion, and elevated the urinary Na/K ratio in rats. These effects were more potent than those of the other diuretics furosemide, trichlormethiazide, indapamide and spironolactone. Moreover, Torasemide exhibited a similar or higher urinary Na/K ratio than the combination of these diuretics and spironolactone. In a study employing anaesthetized dogs, i.v. injection of Torasemide resulted in a higher urinary Na/K ratio in comparison to furosemide, in addition to potent and long-lasting diuretic activity.