[Congestive heart failure in Spain: cost-effectiveness and cost-benefit analyses of treatment with beta-blockers]. / Análisis coste-efectividad y coste-beneficio del tratamiento con bloqueadores beta de la insuficiencia cardíaca congestiva en España.

OBJECTIVE: Beta-blockers (BB) have proven to be effective in the treatment of congestive heart failure (CHF). This study is an economic analysis for the addition of BB to standard treatment of CHF. PATIENTS AND METHOD: Randomized, double-blinded controlled studies are included, with 1,647 patients treated with bisoprolol, 3,034 treated with carvedilol, 2,432 treated with metoprolol, and 6,807 treated with placebo. Direct costs of BB treatment and of every hospitalization episode are assessed. Cost-effectiveness is assessed as cost in euros by prevented death, and cost-benefit as the difference between hospitalization costs and BB costs. The study is conducted from the perspective of a third-party payer. RESULTS: Two studies with bisoprolol, six with carvedilol, and five with metoprolol are included, with an average follow-up of 13.5 months. Carvedilol prevents 5.07% of deaths per year of treatment and is more effective than bisoprolol (3.82% of avoided deaths) and metoprolol (3.03%). Cost-effectiveness ratio (cost for every prevented death and year) was 10,832 euros for bisoprolol, 17,516 euros for carvedilol and 16,664 euros for metoprolol. Incremental cost-effectiveness ratio for carvedilol ranges between 12,631 euros and 86,610 euros for life saved. All BB generate costs saving for hospitalization but only bisoprolol provides a net profit. Benefit-cost index is 1.13 for bisoprolol, 0.26 for carvedilol and 0.59 for metoprolol. CONCLUSIONS: Use of BB in the treatment of CHF is an effective and cost-effective alternative. Carvedilol is the most effective alternative, and bisoprolol the most cost-effective alternative and the drug with greater benefit-cost index.

Análisis coste-efectividad y coste-beneficio del tratamiento con bloqueadores beta de la insuficiencia cardíaca congestiva en España / Congestive heart failure in Spain: cost-effectiveness and cost-benefit analyses of treatment with beta blockers

Objetivo. Los bloqueadores beta (BB) han demostrado ser eficaces en el tratamiento de la insuficiencia cardíaca congestiva (ICC). Este estudio lleva a cabo un análisis económico de añadir BB al tratamiento convencional de la ICC. Material y método. Se incluyen estudios aleatorizados, con grupo control y doble ciego, que incluyeron 1.647 pacientes en tratamiento con bisoprolol, 3.034 con carvedilol, 2.432 con metoprolol y 6.807 con placebo. Se valoran los costes directos del tratamiento BB y de cada episodio de hospitalización. El coste-efectividad se valora como coste en euros por muerte evitada y el beneficio-coste como la diferencia entre costes de hospitalización y costes del BB. El estudio se realiza desde la perspectiva de un tercer pagador. Resultados. Se incluyen 2 estudios con bisoprolol, 6 con carvedilol y 5 con metoprolol con un seguimiento medio de 13,5 meses. Carvedilol evita un 5,07% de las muertes por año de tratamiento y es más eficaz que bisoprolol (3,82% de muertes evitadas) y metoprolol (3,03%). El ratio coste-efectividad (coste por muerte evitada y año) fue 10.832 € para bisoprolol, 17.516 € para carvedilol y 16.664 € para metoprolol. El ratio coste-efectividad incremental de usar carvedilol oscila entre 12.631 € y 86.610 € por vida salvada. Todos los BB generan ahorro en los costes de hospitalización, pero sólo bisoprolol tiene un beneficio neto. El índice beneficio-coste es 1,13 para bisoprolol, 0,26 para carvedilol y 0,59 para metoprolol. Conclusiones. El uso de BB en el tratamiento de la ICC es una alternativa eficaz y coste-efectiva. Carvedilol es la alternativa más eficaz y bisoprolol la más coste-efectiva y con mayor beneficio-coste

Objective. Beta blockers (BB) have proven to be effective in the treatment of congestive heart failure (CHF). This study is an economic analysis for the addition of BB to standard treatment of CHF. Patients and method. Randomized, double-blinded controlled studies are included, with 1,647 patients treated with bisoprolol, 3,034 treated with carvedilol, 2,432 treated with metoprolol, and 6,807 treated with placebo. Direct costs of BB treatment and of every hospitalization episode are assessed. Cost-effectiveness is assessed as cost in euros by prevented death, and cost-benefit as the difference between hospitalization costs and BB costs. The study is conducted from the perspective of a third-party payer. Results. Two studies with bisoprolol, six with carvedilol, and five with metoprolol are included, with an average follow-up of 13.5 months. Carvedilol prevents 5.07% of deaths per year of treatment and is more effective than bisoprolol (3.82% of avoided deaths) and metoprolol (3.03%). Cost-effectiveness ratio (cost for every prevented death and year) was 10,832 € for bisoprolol, 17,516 € for carvedilol and 16,664 € for metoprolol. Incremental cost-effectiveness ratio for carvedilol ranges between 12,631 € and 86,610 € for life saved. All BB generate costs saving for hospitalization but only bisoprolol provides a net profit. Benefit-cost index is 1.13 for bisoprolol, 0.26 for carvedilol and 0.59 for metoprolol. Conclusions. Use of BB in the treatment of CHF is an effective and cost-effective alternative. Carvedilol is the most effective alternative, and bisoprolol the most cost-effective alternative and the drug with greater benefit-cost index

Cost-effectiveness analysis of bisoprolol treatment for heart failure.

BACKGROUND: Beta-blockers have provided evidence of improving survival in chronic heart failure patients. Specifically, the Cardiac Insufficiency Bisoprolol Study II has shown a significant reduction in mortality and morbidity among patients with moderate to severe chronic heart failure treated with bisoprolol. Our aim was to investigate the economic consequence of bisoprolol therapy in chronic heart failure patients in Italy. METHODS: Data were derived from the Cardiac Insufficiency Bisoprolol Study II trial. We conducted a cost-effectiveness analysis, comparing standard care with bisoprolol vs standard care with placebo in the perspective of the Italian National Health Service. We identified and quantified medical costs: drug costs according to the Italian National Therapeutic Formulary; specialist visits for initiation and up-titration of bisoprolol therapy and hospitalizations were quantified based on the Italian National Health Service tariffs (2005). Effects were measured in terms of mortality and morbidity reduction (number of deaths, life-years gained and frequency of hospitalizations). We considered an observational period of 1.3 years, i.e. the average follow-up recorded in the trial. Discounting was not performed because of the relatively short follow-up of patients. We conducted one- and multiway sensitivity analyses on unit cost and effectiveness. We also conducted a threshold analysis. RESULTS: The overall cost of care per 1000 patients treated for 1.3 years was estimated in Euro 2,075,548 in the bisoprolol group and in Euro 2,396,265 in the placebo group, resulting in a net saving of Euro 320,718. The number of additional patients alive with bisoprolol was 55 per 1000 patients, the number of lifeyears gained was 36 at 1.3 year. CONCLUSIONS: Bisoprolol therapy is dominant since it is both less costly and more effective than standard care. Results of sensitivity analysis showed that bisoprolol therapy remains dominant even to changes in unit cost of drug and hospitalizations.

Cost-effectiveness of differing perioperative beta-blockade strategies in vascular surgery patients.

OBJECTIVES: To determine the incremental value of different strategies of both oral and intravenous beta-blockade during the perioperative period in high-risk vascular patients in reducing costs and improving outcomes. DESIGN: Decision analytic model incorporating costs from provider's perspective INTERVENTIONS: Five perioperative strategies in patients undergoing abdominal aortic aneurysm surgery: (1). no routine beta-blockade, (2). preoperative oral bisoprolol for 7 days followed by perioperative intravenous metoprolol and oral bisoprolol based on preoperative titration, (3). immediate preoperative atenolol with postoperative intravenous then oral atenolol, (4). intraoperative esmolol and postoperative intravenous then oral atenolol, and (5). intraoperative and 18 hours of postoperative esmolol then atenolol. MEASUREMENTS AND MAIN RESULTS: Perioperative death was associated with a net increase of US dollars 21909 in charges to Medicare, whereas sustaining a perioperative myocardial infarction was associated with a net increase in charges of US dollars 15000. There is a net hospital saving of US dollars 500 using a strategy of titration of an oral beta-blocker medication for a minimum of 7 days, with a net increase in efficacy of 0.0304. All of the strategies involving acute perioperative blockade were associated with a net cost savings and increase in efficacy, although less than the strategy involving preoperative oral titration. CONCLUSION: Perioperative beta-blockade is both cost effective as well as efficacious from a short-term provider perspective. The optimal strategy of treatment for patients who do not present to surgery already on beta-blockers requires further study, although all strategies save money even accounting for pharmaceutical costs.

In heart failure, all beta-blockers are not necessarily equal.

The Carvedilol or Metoprolol European Trial (COMET; Lancet 2003; 362:7-13) found that in patients with heart failure, survival appears to be better with carvedilol than with immediate-release metoprolol tartrate. Whether the target doses used were equivalent (carvedilol 25 mg twice daily vs metoprolol tartrate 50 mg twice daily) has been debated, but the COMET trial shows that drugs in the same class do not necessarily have the same effects. Given the overwhelming evidence of the benefit of carvedilol, metoprolol succinate, and bisoprolol in patients with heart failure, we should all strive to increase the use of these drugs in appropriate doses.

[Cost-effectiveness of bisoprolol in chronic heart failure]. / Kostnadseffektivt att behandla kronisk hjärtsvikt med bisoprolol.

The cost-effectiveness of adding the beta blocker bisoprolol to standard treatment in patients with congestive heart failure was investigated, based on data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II). The medical resource consumption from CIBIS II was combined with Swedish cost data for medication and hospitalisations. Costs of added years of life, i.e. consumption net of production, were also included in the analysis. The health effects were measured in terms of gained years of life. The results of the analysis show that the cost-effectiveness of bisoprolol compares favourably with that of other cardiovascular treatments. Without the inclusion of costs of added years of life, the cost-effectiveness was in the range of SEK 3,351-13,096 per gained year of life, and with the costs of added years of life included, the cost-effectiveness was in the range of SEK 137,533-147,278 per gained year of life.

Cost effectiveness of bisoprolol in the treatment of chronic congestive heart failure in Sweden: analysis using data from the Cardiac Insufficiency Bisoprolol Study II trial.

OBJECTIVE: To investigate the cost effectiveness of adding the beta-blocker bisoprolol to standard treatment in patients with congestive heart failure (CHF). DESIGN AND SETTING: A cost-effectiveness study was based on the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), a randomised clinical trial investigating the efficacy of adding bisoprolol to standard therapy of CHF. The cost-effectiveness analysis was carried out from a societal perspective. METHODS: Health effects were measured in terms of years of life gained. On the cost side, treatment costs for pharmaceuticals and hospitalisations were included. Data on healthcare resource consumption from CIBIS-II were used and were combined with average Swedish retail prices for medicines, and average costs for hospitalisations based on hospital admissions, in the base case. The costs of added years of life, i.e. consumption net of production during life-years gained were also included. RESULTS: If costs of added years of life were not included, then bisoprolol therapy increased life expectancy at an incremental cost of Swedish kronor (SEK) 13 094 (1999 values) per year of life gained. If costs of added years of life were included, then the incremental cost-effectiveness ratio of bisoprolol therapy was SEK 168 858 per year of life gained. CONCLUSIONS: For patients with CHF with the characteristics of those in CIBIS-II, the cost effectiveness of bisoprolol therapy compares favourably with that of other cardiovascular therapies.

[Bisprolol in heart failure: efficacy and costs in a French setting according to CIBIS II]. / Bisoprolol dans l'insuffisance cardiaque: efficacité et coûts dans le cadre français selon CIBIS II.

After a significant mortality benefit with bisoprolol in heart failure was demonstrated in CIBIS-II, an economic evaluation has been performed in cost-effectiveness terms. Average direct costs per patient were based on clinical data from 231 French patients, and measured in the perspective of the French National Health Insurance, effectiveness being expressed in terms of life days gained per patient. The extra cost of bisoprolol treatment and follow-up (averaging FF 1300 per 1.3 years) is outweighed by the reduction in hospitalization costs (representing a saving of FF 10,500 per patient) and other medication costs. Finally, bisoprolol therapy induces benefits in terms of both cost and survival: on average FF 9500 and 11 life days per patient. Sensitivity analyses confirm these results.

Reduced costs with bisoprolol treatment for heart failure: an economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II).

BACKGROUND: Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). METHODS: Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS II. These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per diem (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. RESULTS: Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions per patient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per diem analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound4987 vs pound4722 in the U.K. The diagnosis related group analysis gave similar results. INTERPRETATION: Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This 'win-win' situation of positive health benefits associated with cost savings is favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure.

Economic impact of beta blockade in heart failure.

We reviewed the literature on clinical trials of beta-adrenergic blockade for treatment of heart failure, seeking evidence of reductions in hospital admissions. To analyze the economic implications of six clinical trials, we developed a stochastic cost model to generate estimates of total medical costs resulting from heart failure and related causes. The model includes inpatient, outpatient, and professional cost estimates based on Medicare claims data, and it is driven by traditional endpoint statistics reported in the clinical trial literature. It provides a common framework for comparing cost effectiveness across clinical trials in the absence of detailed cost information collected in the trial. The incremental expected cost per year of life saved is $3,300 for bisoprolol, $2,500 for metoprolol, and $6,700 for carvedilol. The cost per year of life saved for each compound is well below accepted standards for cost effectiveness. These results are sensitive to the cost of drug therapy and the relative mortality rate for the experimental group. For example, if the relative mortality rate of the experimental group were to increase from the reported 40% to 82%, and if the annual cost of the drug were to decrease from $2,000 to $500, then we estimate that carvedilol would break even and the cost per year of life saved would drop to zero. Whether beta-blocker therapy, as assumed, sustains its differential effectiveness in terms of relative mortality risk beyond the study duration has not been demonstrated.

A cost-effectiveness analysis of bisoprolol for heart failure.

AIMS: This study considers the cost-effectiveness of bisoprolol in heart failure patients as an adjunctive therapy to usual treatment. METHODS AND RESULTS: A cost-effectiveness model was constructed using data available from the CIBIS I & II trials and other secondary sources. Differences in patient survival rates were calculated for bisoprolol (n=1327) and placebo groups (n=1320) extrapolating data over a 5-year period, under limited and extended benefits scenarios to calculate life years gained (LYG). Hospitalisation rates were calculated using data from both CIBIS trials. Costs were considered under two different patient management protocols for treatment initiation - shared care by outpatient clinics and GPs and initiation by a nurse working in the community. Discounted LYG were calculated to be 0.228 under the limited benefits scenario and 0.368 under the extended benefits scenario. Under the extended benefits scenario shared care resulted in a cost of pound268 per LYG or pound412 per LYG for community initiation. Under the limited benefits scenario the costs were a pound135 saving and pound69, respectively. CONCLUSION: This analysis has shown bisoprolol to be an economically attractive therapy in comparison with other treatments. It is hoped that its adoption by clinicians will be rapid, despite the labour intensive and time consuming up-titration process involved in its initiation.

[Cost effectiveness of bisoprolol in treatment of heart failure in Germany. An analysis based on the CIBIS-II study]. / Wirtschaftlichkeit von Bisoprolol in der Behandlung der Herzinsuffizienz in Deutschland. Eine Analyse auf der Basis der CIBIS-II-Studie.

OBJECTIVES: Economic analysis of bisoprolol plus standard therapy versus placebo plus standard therapy in the treatment of chronic heart failure in Germany. MATERIALS AND METHODS: Prospective analysis of resource use and costs by way of integration into the international, randomized, double-blind CIBIS (Cardiac Insufficiency Bisoprolol Study)-II clinical trial, which treated 1,327 patients with bisoprolol and 1,320 with placebo. Two hundred and fifteen German patients were included in CIBIS-II (bisoprolol: 112, placebo: 103). The German health economic subpopulation comprised 97 patients (bisoprolol: 52, placebo: 45). The economic base analysis valued the resource use of every single patient of this subpopulation in monetary terms, from the perspective of Germany's third party payer (statutory sick funds). RESULTS: Mean observation time was 1.3 years. During this time hospitalization costs of DM 783.--were saved in the bisoprolol group. Total direct medical costs amounted to DM 7,651.--in the bisoprolol group and DM 8,905.--in the placebo group. This means savings of DM 1,254.--per patient, or a 14.1% cost reduction. If mean data of all German CIBIS-II patients are used as a broader basis, bisoprolol therapy saves DM 1,203.--per patient. Bisoprolol therapy induced a mortality rate reduction from 17% to 12% in the overall clinical CIBIS-II population (n = 2,647). This difference is statistically highly significant (p < 0.0001). Altogether 74 lives could be saved by bisoprolol therapy. Saved life years amounted to 0.03 per patient after 65 weeks of therapy (460 days), and to 0.12 per patient after 130 weeks (30 months). As bisoprolol therapy leads to net savings, a formal cost-effectiveness analysis, which would relate incremental clinical efficiency to additional costs, is not needed. CONCLUSION: The use of bisoprolol in the therapy of chronic heart failure is not only clinically effective, it also saves net costs.

A cost minimisation analysis of cardiac failure treatment in the UK using CIBIS trial data. Cardiac Insufficiency Bisoprolol Study.

The clinical benefits of beta-blockers in heart failure are currently subject to intense debate and are being investigated. The economic impact of beta-blockade, however, has largely remained unexplored. The Cardiac Insufficiency Bisoprolol Study (CIBIS), while failing to show statistically significant reduction in mortality over conventional therapy, demonstrates that the administration of bisoprolol adjuvant to standard therapy leads to a significant reduction in hospital admission. The present study is a cost minimisation analysis based on CIBIS data for the UK and is restricted to direct costs only. The costs of bisoprolol medication and inpatient treatment of heart failure are considered. The 'base case' analysis and the sensitivity analyses carried on all cost driver parameters show that administering bisoprolol to heart failure patients adjuvantly to the standard therapy is at least cost neutral. Additional drug costs incurred by bisoprolol are compensated by the inpatient treatment costs of heart failure avoided. All other non-quantifiable clinical benefits such as improvement of New York Heart Association functional class are positive extras to patients and the National Health Service.

A cost-minimization of heart failure therapy with bisoprolol in the French setting: an analysis from CIBIS trial data. Cardiac Insufficiency Bisoprolol Study.

Beta-blocker-induced benefit in heart failure is under intense evaluation. Several large-scale mortality trials are currently being performed, with CIBIS II evaluating bisoprolol. The economic impact of beta-blocker therapy in heart failure has not been previously determined. The present study is a cost-effectiveness evaluation of bisoprolol treatment based on CIBIS I data. It considers direct costs, that is, the bisoprolol medication cost and the cost of hospitalization related to heart failure and its complications. Hospitalization costs were calculated from the French system of classification (PMSI), which provides costs according to homogeneous groups of patients (GHM). The cost difference between bisoprolol and placebo in the entire CIBIS population and the trial duration result from an increase in cost caused by bisoprolol treatment (+ 2018 Frs/patient) and a decrease in cost related to reduced hospitalization (6349 Frs/patient). A total savings per patient of about 4330 Frs was produced by bisoprolol. Cost reduction is still more pronounced in patients not having a history of myocardial infarction. We conclude that heart failure therapy with bisoprolol lowers medical healthcare costs, mainly due to the reduced rate of hospital admissions for heart failure.

Economic evaluation of the Cardiac Insufficiency Bisoprolol Study for the Federal Republic of Germany.

The Cardiac Insufficiency Bisoprolol Study (CIBIS) demonstrates that, for patients with heart failure of different aetiologies, administration of the beta 1-adrenoceptor blocker bisoprolol as an adjuvant to the standard therapy leads to a significant avoidance of hospital admissions. A pharmacoeconomic analysis of the results of the CIBIS was conducted for the Federal Republic of Germany, and was restricted to direct costs only. The costs of bisoprolol medication and inpatient treatment of heart failure were considered, the latter forming the major part of costs incurred. Per 1000 patient-years, adjuvant bisoprolol therapy resulted in overall cost savings of Deutschmarks (DM)157,272. Statutory Health Insurance had a net saving of DM186,719 in 1000 patient-years, while patients experienced additional net expenses of DM17,760 over 1000 patient-years. The economic advantage of adjuvant bisoprolol treatment was also borne out in the sensitivity analysis. Adjuvant therapy with bisoprolol was not only clinically beneficial for the patient with heart failure but was also economically advantageous.

[Cost effectiveness of bisoprolol in heart failure. Economic evaluation of the Cardiac Insufficiency Bisoprolol Study (CIBIS) for Germany]. / Wirtschaftlichkeit von Bisoprolol bie Herzinsuffizienz. Okonomische Bewertung der Cardiac Insufficiency Bisoprolol Study (CIBIS) für die Bundesrepublik Deutschland.

BACKGROUND: The Cardiac Insufficiency Bisoprolol Study (CIBIS) demonstrates that, for patients with heart failure of different etiologies, the administration of the beta(1)-adrenoceptor blocker bisoprolol adjuvant to the standard therapy leads to a significant avoidance of hospital admissions. PHARMACOECONOMIC EVALUATION: The results of the CIBIS were evaluated pharmacoeconomically for the Federal Republic of Germany, and were restricted to direct costs only. The costs of bisoprolol medication and in-patient treatment of heart failure were considered, the latter forming the major part of costs incurred. CONCLUSION: Adjunctive therapy with bisoprolol is not only clinically beneficial to the patient with heart failure, but also economically advantageous.