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Erschienen in:
01.06.2001 | Adis Pharmacoeconomic Drug Evaluation
Torasemide
A Pharmacoeconomic Review of its Use in Chronic Heart Failure
Erschienen in: PharmacoEconomics | Ausgabe 6/2001
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Abstract
Torasemide is a loop diuretic used for the treatment of hypertension and for oedema in chronic heart failure (CHF), renal failure and cirrhosis. The efficacy of torasemide in reducing salt and water retention in CHF has been established in double-blind comparative studies against furosemide. Torasemide has been shown to be at least as effective as furosemide in terms of total volume of urine excreted and also has a longer duration of action. The efficacy of torasemide (in terms of improved CHF symptoms and reduced pulmonary congestion, oedema and bodyweight) has been shown in randomised controlled trials and confirmed in large postmarketing studies. In addition, data from postmarketing studies have shown that patients receiving torasemide had significantly reduced hospital admission rates compared with patients receiving furosemide.
Pharmacoeconomic assessments of torasemide have focused on its effect in reducing hospitalisation. Hospitalisation costs due to CHF decreased by 86% during the 11.2-month period of torasemide treatment, compared with the 6-month period prior to treatment, in a US retrospective study assessing medical and pharmacy claims data. Overall, average monthly costs for patients decreased by 56.6% after 5.1 months (from $US1897.28 to $US823.70 per patient per month; PPPM), and by 76% after 11.2 months (from $US1944.76 to $US470.76 PPPM) of torasemide treatment. In the furosemide group, average monthly costs for patients increased moderately from $US227.28 to $US261.18 PPPM after 12 months. Direct comparison of the torasemide and furosemide study groups was not possible because the group receiving torasemide had much higher healthcare resource use at baseline.
Compared with furosemide, torasemide was associated with reduced rates of hospital admissions for CHF and/or cardiovascular causes in 3 studies, a retrospective analysis conducted in Germany, a prospective US study of patients enrolled from hospital admissions and a decision-analysis model. As a result, the direct costs of treatment for CHF or cardiovascular diseases for patients treated with torasemide were less than those with furosemide. However, in the US study, there was no statistically significant difference in hospital admissions for all causes and/or in overall direct medical costs, although the study was not powered to show this. In another US study of managed care patients with New York Heart Association (NYHA) class II or III CHF, no difference in clinical or economic outcomes was observed between patients taking torasemide or furosemide; despite the higher acquisition costs for torasemide, total costs were similar for both groups.
Torasemide was found to be more cost effective than furosemide in terms of cost per patient with improved functional (NYHA) class of CHF severity in a retrospective German analysis, although this measure is not ideal. This study also evaluated indirect costs (for loss of productivity of employed patients) and results suggest torasemide has a favourable effect in reducing days off work compared with furosemide, although the population of employed patients in the study was very small.
Torasemide has been shown to improve some measures of quality of life in 2 studies. It was associated with higher quality-of-life scores than furosemide in a 6-month study, but the differences were only significant at month 4. In another study, torasemide significantly improved fatigue, but full study details are yet to be published.
Conclusions: Despite the higher acquisition cost of torasemide over furosemide, pharmacoeconomic analyses have shown that torasemide is likely to reduce overall treatment costs of CHF by reducing hospital admissions and readmissions. Torasemide has generally shown clinical and economic advantages over furosemide, although more long term data are needed to confirm these results and to further investigate effects on quality of life. There are limitations to the currently available pharmacoeconomic data, but present data support the use of torasemide as a first-line option for diuretic therapy in patients with CHF presenting with oedema and especially in those patients not achieving relief of symptoms with furosemide.
Overview of Chronic Heart Failure
Chronic heart failure (CHF) is characterised by impaired cardiac function in which the heart is unable to pump adequately and provide sufficient blood to the systemic circulation. CHF affects around 1 to 3% of the adult population, with two-thirds of those affected aged over 70 years. The prevalence of CHF in individuals over 80 years of age is >10%.
The high morbidity and mortality of CHF places a large economic burden on healthcare systems. CHF is the most common cause of hospitalisations in people over 65 years of age. The median survival following onset of CHF is 1.7 years in men and 3.2 years in women.
Diuretics are used in CHF if pulmonary and/or peripheral oedema are present as these drugs can improve symptoms of breathlessness and ankle swelling. Loop diuretics maintain their efficacy unless renal function is severely impaired (creatinine clearance <5 ml/min; <0.3 L/h) and are therefore preferred over thiazide diuretics in most patients with CHF requiring diuretic therapy. However, even in patients whose symptoms of CHF are well controlled, diuretics are not used alone and are generally combined with an angiotensin converting enzyme (ACE) inhibitor and a α-blocker in patients with CHF caused by left ventricular systolic dysfunction. The management of diastolic dysfunction is less straightforward; diuretics and nitrates are considered the drugs of choice for symptomatic patients, but various other agents may also be used. Nonpharmacological treatment such as revascularisation surgery and heart transplantation are also used in the management of CHF.
The cost of treating CHF accounts for 1 to 2% of total healthcare expenses in developed countries. Hospitalisation contributes to a large proportion of costs and can account for as much as 60 to 70% of total medical costs. In the US, the estimated direct and indirect costs of CHF amount to $US22.5 billion annually (2000 values).
Clinical Profile of Torasemide
The diuretic efficacy of torasemide has been established in randomised double-blind comparative studies with furosemide. Oral dosages of 5 and 10 mg/day of torasemide have diuretic efficacy similar to that of furosemide 40 mg/day, and torasemide 20 mg/day has greater diuretic efficacy than furosemide 40 mg/day. Clinical trials have also shown that 5 and 10 mg/day dosages of torasemide improve pulmonary and cardiac haemodynamics over the short and medium term
A large German postmarketing study of 1740 patients with CHF compared the 6-month period prior to initiation of torasemide with the 6-month period after initiation of torasemide. At the end of the study period, severity of CHF had improved in 75% of patients and there was a significant decrease in hospitalisation rates. In patients pre-treated with furosemide (n = 418), 78 (18.7%) were hospitalised while receiving furosemide in the 6 months prior to the study, but only 9 (2.2%) were hospitalised in the 6 months after torasemide treatment was initiated (p < 0.001). Furthermore, an Italian study retrospectively analysed hospital admission rates in 62 consecutive patients hospitalised for CHF. The number of hospital admissions and inpatient days were lower in torasemide-treated than furosemide-treated patients. Torasemide has also been associated with lower mortality rates than furosemide in a large prospective study of 2303 patients with CHF conducted in Spain (published only as an abstract).
Commonly reported adverse events from clinical trials included hypokalaemia, hyperuricaemia, fatigue, dizziness, headache, GI disturbance, orthostatic hypotension, muscle cramps, lower back pain, skin rash and nausea. These adverse events were usually only transient and rarely necessitated drug withdrawal.
Pharmacoeconomic Analyses
The effect of torasemide on healthcare resource use and costs, particularly those related to hospitalisations, has been assessed in 1 decision-analysis model, 2 retrospective and 2 prospective pharmacoeconomic analyses. In all studies treatment with torasemide was compared with furosemide. Most studies were cost analyses, although one was a cost-effectiveness analysis.
The decision-analysis model compared the direct medical costs in hypothetical CHF patients with mild to moderate disease treated with torasemide or furosemide in the first year following diagnosis. Torasemide was associated with higher acquisition costs ($US190.74 vs $US25.17 per patient per year, 1994/95 values) but lower hospitalisation costs ($US364.65 vs $US583.88 per patient per year) than furosemide. Overall, the model predicted that torasemide treatment would realise cost savings of $US113.81 per patient per year compared with furosemide.
In a US retrospective study, direct comparison of the torasemide and furosemide study groups was not performed, as the group receiving torasemide had much higher healthcare resource utilisation at baseline. However, in this cost analysis comparisons were made within study groups, comparing the period after initiation of the study drugs with the period prior to the initiation of the study drugs. The introduction of torasemide decreased costs due to hospitalisation by 86% during an 11.2-month period, compared with the 6 months prior to its introduction, whereas furosemide had no effect on hospitalisation rate or associated costs. Overall, average monthly costs for patients decreased by 56.6% after 5.1 months (from $US1897.28 to $US823.70 per patient per month; PPPM), and by 76% after 11.2 months (from $US1944.76 to $US470.76 PPPM) of torasemide treatment. In the extended study of torasemide to 11.2 months, costs during the 6-month pre-introduction period were different to those in the same 6-month period of the original study ($US1944.76 vs $US1897.28) because they were based on slightly different patient numbers. In the furosemide group, average monthly costs for patients increased moderately from $US227.28 to $US261.18 PPPM after 12 months.
Torasemide was found to be more cost effective than furosemide in terms of cost per patient with improved functional class of CHF severity in a German retrospective study. Compared with furosemide, torasemide was associated with higher drug costs but this was offset by reduced costs for hospitalisations due to CHF. Hospitalisation costs in the furosemide group were 5 times higher per patient than in the torasemide group. Overall, total direct and indirect costs were lower in patients receiving torasemide than furosemide.
Torasemide and furosemide achieved similar clinical and economic outcomes in aUS prospective study of managed care patients with mild stable CHF. Patients included in this study had low rates of hospitalisation. Despite the higher acquisition costs for torasemide, total costs were similar for both study groups because diuretic drug costs represented a relatively small proportion of overall costs and some of the difference in acquisition costs was offset by a slightly lower rate of CHF-related physician visits and mean length of hospital stay.
In another US prospective study of patients obtained from a hospital setting, the use of torasemide reduced healthcare resource utilisation and costs related to CHF or cardiovascular causes compared with furosemide. Patients treated with torasemide had fewer hospital admissions than those treated with furosemide (18 vs 34% for CHF, 38 vs 58% for any cardiovascular cause, and 67 vs 73% for all causes). Acquisition costs per patient of torasemide over 1 year amounted to $US531 compared with $US13 for furosemide (1998 values). Costs of hospital admissions for CHF, cardiovascular causes and all causes were significantly less for torasemide recipients, but outpatient costs were not significantly different between groups. Overall total costs per patient were less in the torasemide group ($US13 899) than in the furosemide group ($US16 023) but the difference was not statistically significant because of small patient numbers.
Quality-of-Life Effects
CHF has been shown to have a negative impact on patients’ quality of life. Poor quality of life has been associated with more severe symptoms and hospitalisation for CHF
There are few data on the effect of diuretics on quality of life in CHF. Direct measurement of quality of life has been performed in 2 US prospective studies comparing the clinical and economic outcomes of patients treated with torasemide or furosemide. In one study, quality of life improved slightly for patients receiving torasemide and reduced slightly for patients receiving furosemide during the 6-month treatment period. However, the difference in quality-of-life scores between the 2 groups was only significant at 4 months. The study used the disease-specific instrument Minnesota Living with Heart Failure Questionnaire. In the other study, patients treated with torasemide were significantly less fatigued than patients treated with furosemide.