Prospective Clinical Trial Comparing IV Esmolol to IV Metoprolol in CT Coronary Angiography: Effect on Hemodynamic, Technical Parameters and Cost.

BACKGROUND: Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost. MATERIALS AND METHODS: Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality. RESULTS: Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status. CONCLUSION: Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.

Ex Ante Economic Evaluation of Arg389 Genetically Targeted Treatment with Bucindolol versus Empirical Treatment with Carvedilol in NYHA III/IV Heart Failure.

OBJECTIVE: The Beta-Blocker Evaluation Survival Trial showed no survival benefit for bucindolol in New York Heart Association (NYHA) class III/IV heart failure (HF) with reduced ejection fraction, but subanalyses suggested survival benefits for non-Black subjects and Arg389 homozygotes. We conducted an ex ante economic evaluation of Arg389 targeted treatment with bucindolol versus carvidolol, complementing a previous ex ante economic evaluation of bucindolol preceded by genetic testing for the Arg389 polymorphism, in which genetic testing prevailed economically over no testing. METHODS: A decision tree analysis with an 18-month time horizon was performed to estimate the cost effectiveness/cost utility of trajectories of 100%, 50%, and 0% of patients genetically tested for Arg389 and comparing bucindolol with empirical carvedilol treatment as per prior BEST subanalyses. Incremental cost-effectiveness/cost-utility ratios (ICERs/ICURs) were estimated. RESULTS: Race-based analyses for non-White subjects at 100% testing showed a loss of (0.04) life-years and (0.03) quality-adjusted life-years (QALYs) at an incremental cost of $2185, yielding a negative ICER of ($54,625)/life-year and ICUR of ($72,833)/QALY lost; at 50%, the analyses showed a loss of (0.27) life-years and (0.16) QALYs at an incremental cost of $1843, yielding a negative ICER of ($6826)/life-year and ICUR of ($11,519)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Arg389 homozygote analyses at 100% testing showed incremental gains of 0.02 life-years and 0.02 QALYs at an incremental cost of $378, yielding an ICER of 18,900/life-year and ICUR of $18,900/QALY gained; at 50%, the analyses showed a loss of (0.24) life-years and (0.09) QALYs at an incremental cost of $1039, yielding a negative ICER of ($4329)/life-year and ICUR of ($9336)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. CONCLUSION: This independent ex ante economic evaluation suggests that genetically targeted treatment with bucindolol is unlikely to yield clinicoeconomic benefits over empirical treatment with carvedilol in NYHA III/IV HF.

[The effectiveness of carvedilol in heart failure]. / A carvedilol hatásossága szívelégtelenségben.

BACKGROUND: The third generation beta-blocker (carvedilol) is effective in reduction of hypertension, and of mortality and morbidity as a supplement to conventional drugs of heart failure therapies (diuretics, ACE inhibitors), based on randomized controlled trials and retrospective analysis. OBJECTIVE: To analyse the efficacy of carvedilol in the treatment of heart failure with special focused on morbidity, mortality endpoints. METHODS: We assessed the multicenter, randomised, double-blind studies involving more than 150 patients (1995-2005) from MEDLINE database, in which carvedilol was used in the case of moderate to severe heart failure. We also present the results of health-economic publications (2000-2005). RESULTS: In U.S. Carvedilol Heart Failure Study (n 1096) the mortality declined by 65% (3.2% vs. 7.8%; p <0.001) with carvedilol vs. placebo, while the cardiovascular hospitalization decline was 27% (14.1% vs. 19.6%; p = 0.036) in heart failure (LVEF < or = 5%) applied together with the basic therapy (diuretic and ACE-inhibitor). In the COPERNICUS trial the efficacy of carvedilol was compared to placebo in the case of severe HF patients (LVEF < 25%, n = 2889). The annual mortality risk declined by 35% (19.7% vs. 12.8%, 95% CI 19-48%, p = 0.00013) while the risk of mortality or any risk of hospitalisation by 24% (p = 0.00004) in the active group. The CAPRICORN study (LVEF < or = 0%, n=1959) showed that carvedilol is efficacious in reduction of total (HR: 0.77; 95% CI 0.60-0.98; p = 0.031) and cardiovascular mortality (HR: 0.75; 95% CI 0.58-0.96; p = 0.024) as far as high-risk patients are concerned. CONCLUSION: The effectiveness of carvedilol is certified in reduction of mortality and hospitalization in the treatment of moderate-severe heart-failure as part of the combination therapy. The benefits of use of the drug are well measurable not only on the level of patients but on the suppliers and the financer as well, thanks to the decline of resource utilization.

[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.

Carvedilol reduces the costs of medical care in severe heart failure: an economic analysis of the COPERNICUS study applied to the United Kingdom.

BACKGROUND: The aim of this study was to determine the effects of carvedilol on the costs related to the treatment of severe chronic heart failure (CHF). METHODS: Costs for the treatment for heart failure within the National Health Service (NHS) in the United Kingdom (UK) were applied to resource utilisation data prospectively collected in all patients randomized into the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study. Unit-specific, per diem (hospital bed day) costs were used to calculate expenditures due to hospitalizations. We also included costs of carvedilol treatment, general practitioner surgery/office visits, hospital out-patient clinic visits and nursing home care based on estimates derived from validated patterns of clinical practice in the UK. RESULTS: The estimated cost of carvedilol therapy and related ambulatory care for the 1156 patients assigned to active treatment was pound530,771 ( pound44.89 per patient/month of follow-up). However, patients assigned to carvedilol were hospitalised less often and accumulated fewer and less expensive days of admission. Consequently, the total estimated cost of hospital care was pound3.49 million in the carvedilol group compared with pound4.24 million for the 1133 patients in the placebo arm. The cost of post-discharge care was also less in the carvedilol than in the placebo group ( pound479,200 vs. pound548,300). Overall, the cost per patient treated in the carvedilol group was pound3948 compared to pound4279 in the placebo group. This equated to a cost of pound385.98 vs. pound434.18, respectively, per patient/month of follow-up: an 11.1% reduction in health care costs in favour of carvedilol. CONCLUSIONS: These findings suggest that not only can carvedilol treatment increase survival and reduce hospital admissions in patients with severe CHF but that it can also cut costs in the process.

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 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.

Cost-effectiveness analysis of carvedilol for the treatment of chronic heart failure in Japan.

BACKGROUND: The cost-effectiveness of beta-blocker use in patients with chronic heart failure (CHF) has never been elucidated in a Japanese study. METHODS AND RESULTS: A Markov model for outpatients with CHF was constructed to simulate remaining life expectancy and expected medical costs for each patient. Each patient was assumed that they received either carvedilol in addition to conventional therapies (ie, digitalis, diuretics, and angiotensin-converting enzyme inhibitors) or conventional therapies alone. Analyses were conducted both for each patient's remaining lifetime and for a period of 5 years. Analyses were performed from the perspective of Japanese healthcare insurance. Analysis for treatment over the course of each patient's expected life span with carvedilol plus conventional therapies versus conventional therapies alone yielded expected medical costs of 3.5 million yen and 5.5 million yen respectively, and a life expectancy of 121 months and 88 months, respectively. The analysis of a 5-year period yielded 1.4 million yen and 2.8 million yen in expected medical costs and 49 and 45 months life expectancy, respectively, for carvedilol versus conventional therapy. CONCLUSIONS: Carvedilol treatment for CHF patients is a highly cost-effective method of therapy in the Japanese medical environment.

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 beta blocker therapy for patients with chronic severe heart failure in Ireland.

Management of heart failure is estimated to consume 1% to 2% of total healthcare resources and recent data from the UK suggests this may be as high as 4% with hospital admissions accounting for approximately 70% of this expenditure. The safety and efficacy of b-blockers when added to standard therapy i.e. ACE inhibitors in chronic heart failure has recently been demonstrated in large placebo controlled trials. The ability of b-blockers to reduce hospital admission rates would be expected to prove cost effective. In this study the cost effectiveness of the b-blocker carvedilol when added to standard therapy in patients with severe heart failure was determined. Using economic modelling techniques and Irish cost data the incremental cost effectiveness ratio (ICER) for carvedilol therapy was 1,560 Euro per life year gained (LYG). Sensitivity analysis demonstrated an ICER range of 1,560 Euro/LYG to 7,322 Euro/LYG under a variety of assumptions. This suggests that carvedilol therapy for patients with severe chronic heart failure is not only safe and effective but is highly cost effective in the Irish healthcare setting.

Medical resource use and costs of congestive heart failure after carvedilol use.

A retrospective cohort study based on claims and medical chart data was conducted to compare healthcare use and costs in congestive heart failure patients with and without carvedilol. Adult patients with a minimum of two claims with a valid congestive heart failure diagnosis from 1997 to 1999 were included. Patients receiving continuous carvedilol treatment for at least 4 months were considered study case patients. Case patients were matched based on age, gender, race, and concomitant medication. Healthcare use and costs were compared between the case and control groups. A total of 128 case and 147 control patients were identified. There were no significant differences in demographic characteristics, concomitant medication, or New York Heart Association classification between these two groups. Analysis of variance and chi-square analyses were conducted for continuous and categorical variables, respectively. Statistical adjustments were made using a multivariate model. Carvedilol had a significant economic reduction in the overall expenditures by approximately $14,530. Facility expenditures were approximately $9,000 lower for the carvedilol group than for the control group. Carvedilol-treated patients had less frequent hospital admissions and shorter lengths of stay compared with patients not receiving carvedilol. Congestive heart failure patients receiving carvedilol have significantly less healthcare use and costs than patients not receiving carvedilol.

Reimbursement claims analysis of outcomes with carvedilol and metoprolol.

OBJECTIVE: To compare resource use and costs in heart failure (HF) patients receiving metoprolol, a selective beta1-receptor blocker, with carvedilol, which blocks beta1-, beta2-, and alpha1-adrenergic receptors, by use of a retrospective reimbursement-claims analysis. METHODS: Resource use and cost data were extracted for patients diagnosed with HF and treated with carvedilol or metoprolol for 6 months after the initiation of the respective therapy, by use of claims submitted to 6 healthcare plans. A modified Charlson index was used to assess comorbidity. Stepwise logistic regression was used to measure the influence of treatment on hospitalization. RESULTS: Claims from 139 carvedilol and 106 metoprolol patients showed that carvedilol patients experienced significantly fewer total hospitalizations (36.0% vs. 62.3%, respectively; p < 0.001) and emergency department visits (23.7% vs. 42.5%, respectively; p = 0.002) and a trend for fewer HF-related (7.9% vs. 14.2%, respectively; NS) and cardiac-related hospitalizations (15.1% vs. 24.5%, respectively; NS). Treatment with carvedilol was associated with a significant decrease in the risk of any hospitalization (adjusted odds ratio 0.35, 95% CI 0.20 to 0.63; p <0.001). Higher pharmacy costs (mean $1677 vs. $1322; p <0.001) and lower total costs (mean $8100 vs. $14475; p = 0.025) were observed in carvedilol-treated compared with metoprolol-treated patients, respectively. CONCLUSIONS: Compared with metoprolol, the more comprehensive adrenergic blockade achieved with carvedilol may translate into greater clinical benefits in patients with HF. Despite higher pharmacy costs, lower total costs were observed in carvedilol-treated patients.

Cost-effectiveness of beta-blocker therapy with metoprolol or with carvedilol for treatment of heart failure in Canada.

OBJECTIVE: The purpose of this study was to estimate the cost-effectiveness of beta-blocker therapy with either metoprolol or carvedilol in addition to conventional therapy for patients with heart failure (HF) in Canada. DESIGN: A Markov simulation was used to estimate the costs and life expectancy for treating patients with conventional therapy alone and with the addition of metoprolol or carvedilol. Although carvedilol has been marketed in Canada since 1999, metoprolol succinate has yet to be marketed there, so the price is unknown. Therefore we input a Canadian price based on the price ratio of the 2 drugs in the United States. RESULTS: For subjects aged 60 years at HF onset, the expected years of life are 4.53 years for those treated with conventional therapy alone, 5.70 years for those who receive conventional therapy plus metoprolol, and 6.21 years for those who receive conventional therapy plus carvedilol. The expected costs (in 1999 Canadian dollars) are $8,989, $13,833, and $18,114, respectively. This yields incremental cost-effectiveness ratios (ICERs) for metoprolol relative to conventional therapy alone of $4,140 per life-year gained, and for carvedilol relative to metoprolol, the ICER is $8,394 per life-year gained. CONCLUSIONS: In addition to conventional therapy with furosemide and angiotensin converting enzyme inhibitors, treatment with either metoprolol or carvedilol confers a survival benefit that is attractive from a cost-effectiveness point of view. Until better information becomes available, it is not possible to distinguish between the two beta-blockers on the basis of cost-effectiveness. This means that the choice of beta-blockers for HF should be based largely on clinical considerations because both beta-blockers prolong life at relatively low cost.

Cost-effectiveness results from the US Carvedilol Heart Failure Trials Program.

OBJECTIVE: To evaluate the cost-effectiveness of carvedilol, a beta-blocker that is approved for use in the US for the treatment of heart failure, based on data from Phase III clinical trials. METHODS: We conducted an economic evaluation alongside the US Carvedilol Heart Failure Trials Program, which consisted of four concurrent, randomized, double-blind, placebo-controlled clinical trials; the mean duration of follow-up across these four trials was 6.5 months (the program was terminated prematurely based on a finding of a 65% mortality benefit). Using data from these trials, we examined the cost-effectiveness of carvedilol in terms of the estimated cost per death averted among patients randomized to such therapy versus those receiving placebo. Attention was focused on the cost of carvediol therapy plus the cost of cardiovascular-related inpatient care. Costs of care were estimated by combining infomation on healthcare utilization from the clinical trials with secondary sources of cost data. RESULTS: Patients randomized to receive carvedilol had lower mean +/- SD estimated costs of cardiovascular-related inpatient care over 6.5 months compared with those receiving placebo ($1912 +/- $7595 vs. $4463 +/- $20,565, respectively). As mortality alsowas lower among carvedilol patients, the estimated cost per death averted was negative. The probability that carvedilol would both increase survival and decrease costs of cardiovascular-related care over a 6.5-month period was estimated to be 0.98. CONCLUSIONS: Data from the US Carvedilol Heart Failure Trials Program indicate that carvedilol reduces mortality in patients with heart failure; our study suggests that it also may be cost-saving over a period of approximately six months.

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.

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.

[Economic study of carvedilol in heart failure. A cost effectiveness study in France]. / Etude économique du carvédilol dans l'insuffisance cardiaque. Une étude coût-efficacité appliquée à la France.

A programme of four phase III clinical trials carried out in the USA on 1094 patients showed that Carvedilol, associated with the usual bitherapy and eventually with digitalis, reduced the mortality and number of hospital admissions of patients with cardiac failure. These results, transposed to the French population, may be used to evaluate the economic advantages of Carvedilol by developing a cost-effectiveness study which consists in relating the direct expenses (drugs and hospital admissions) of each of the two strategies, with or without Carvedilol, to their respective mortalities. Hospital expenses were estimated with respect to the H.M.G. corresponding to each hospital stay at 1997-1998 values. The cost in the Carvedilol group was 2,823 FF per patient (including 1,491 FF for the drug itself) but 2,056 FF were economised in hospital expenses. With an increased cost of 767 FF but a 50% reduction in mortality corresponding to a difference in mortality of 45@1000, the cost-effectiveness of Carvedilol was 17,040 per life saved and 2,130 FF per additional year of life expectancy. A study of the sensitivity produced even more favourable results of Carvedilol. An evaluation of hospital expenses on the basis of AP-HP data indicates that the addition of Carvedilol is associated with a 4,425 FF reduction in hospital expenses, which makes it a cost saving strategy.