Torasemide in chronic heart failure: results of the TORIC study

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 mgyday orally (ns778) vs. patients who received furosemide 40 mgyday orally (ns527) or other diuretics (ns72) 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 (ns17, 2.2%) than in the furosemideyother diuretics group (ns27, 4.5%) (P-0.05). Functional improvement as assessed by NYHA class was observed in more patients who received furosemide torasemide (ns356, 45.8%) than those who received furosemideyother diuretics (ns223, 37.2%) (Ps0.00017). At the end of the study abnormally low serum potassium levels were observed in fewer torasemide (ns95, 12.9%) than furosemideyother diuretics patients (ns102, 17.9%) (Ps0.013). 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 furosemideyother 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 furosemideyother diuretics.

Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

“…Although furosemide is commonly used in clinical settings, its main complication is that patients with CHF develop resistance to loop diuretics due to a reduction in the glomerular filtration rate and an increase in sodium reabsorption at diuretic-insensitive sites in the nephron [6,10,11,28]. Additionally, furosemide activates the renin-angiotensinaldosterone (RAA) system and the sympathetic nervous system [14,16,32].In contrast to furosemide, previous studies have revealed that long-acting loop diuretics have clinical efficacy; they cause less activation of the RAA system, reduce diuretic resistance, improve ventricular fibrosis and decrease the mortality rate in both humans and animal models [7,17,23,37]. Furosemide treatment for 14 days leads to diuretic resistance in dogs, but this does not occur with torasemide [17].…”

Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice

“…The small GTPase-Rac1, which contributes to the generation of reactive oxygen species (ROS) by coupling to NOX1 [45], the connective tissue growth factor, the lysyl oxidase and miR-21 contribute to the aldosterone-induced signal transduction during the pathogenesis of atrial remodeling [19][20][21]25] + [26]. Here, the experiments in primary cardiac fibroblasts and 37.2%, p < 0.00017) and that fewer patients receiving torsemide died (2.2% vs. 4.5%, p < 0.05) [5]. Additionally, a recent meta-analysis suggests improved functional status and mortality with torsemide compared with furosemide [46].…”

“…Both diuretics exert similar diuretic effects [2,3] but their effect on clinical outcomes remains uncertain. Interestingly, previous studies have reported that torasemide -but not furosemide -decreased collagen volume fraction in the hearts of patients with chronic heart failure (CHF) [4], and early evidence suggests that torasemide treatment was associated with lower mortality compared to furosemide in the TORasemide In Chronic heart failure (TORIC) study [5].…”

Influence of diuretic therapy on the features of heart rhythm variability changes in chronic heart failure patients

“…Эти свойства определяют его повышенную эффективность у пациентов с ХСН, которая продемонстрирована в ряде контролируемых клинических исследо-ваний [4][5][6][7][8][9][10][11][12][13]. Эффективность торасемида обусловлена не только диуретическим эф-фектом, но и антиальдостероновыми меха-низмами.…”