Cost-effectiveness of implantable ventricular assist devices in older children with stable, inotrope-dependent dilated cardiomyopathy.

BACKGROUND: In a stable, inotrope-dependent pediatric patient with dilated cardiomyopathy, we evaluated the cost-effectiveness of continuous-flow VAD implantation compared to a watchful waiting approach using chronic inotropic therapy. METHODS: We used a state-transition model to estimate the costs and outcomes of 14-year-old (INTERMACS profile 3) patients receiving either VAD or watchful waiting. We measured benefits in terms of lifetime QALYs gained. Model inputs were taken from the literature. We calculated the ICER, or the cost per additional QALY gained, of VADs and performed multiple sensitivity analyses to test how our assumptions influenced the results. RESULTS: Compared to watchful waiting, VADs produce 0.97 more QALYs for an additional $156 639, leading to an ICER of $162 123 per QALY gained from a healthcare perspective. VADs have 17% chance of being cost-effective given a cost-effectiveness threshold of $100 000 per QALY gained. Sensitivity analyses suggest that VADs can be cost-effective if the costs of implantation decrease or if hospitalization costs or mortality among watchful waiting patients is higher. CONCLUSIONS: As a bridge to transplant, VADs provide a health benefit to children who develop stable, inotrope-dependent heart failure, but immediate implantation is not yet a cost-effective strategy compared to watchful waiting based on commonly used cost-effectiveness thresholds. Early VAD support can be cost-effective in sicker patients and if device implantation is cheaper. In complex conditions such as pediatric heart failure, cost-effectiveness should be just one of many factors that inform clinical decision-making.

Levosimendan: new indications and evidence for reduction in perioperative mortality?

PURPOSE OF REVIEW: In the last years, the perioperative use of levosimendan in cardiac surgery patients is spreading. Moreover, newer indications have been suggested such as the treatment of sepsis-associated myocardial dysfunction. In the present review, we discuss the most recent evidences in these settings. RECENT FINDINGS: Levosimendan has been seemingly confirmed to reduce mortality in patients undergoing cardiac surgery. In particular, it appears to be the only inotropic drug to have a favorable effect on survival in any clinical setting. Moreover, levosimendan has been shown to exert a cardioprotective action and to reduce acute kidney injury, renal replacement therapy, and ICU stay in cardiac surgery patients. Finally, levosimendan has been suggested to reduce mortality in patients with severe sepsis and to improve renal outcomes in critically ill patients. SUMMARY: Although a strong rationale likely exists to use levosimendan in the setting of perioperative and critical care medicine, evidence mainly comes from small and often poor-quality randomized clinical trials, whose results acquire significance only when pooled in meta-analyses. Moreover, some aspects related to which subgroups of patients may derive the most benefits from receiving levosimendan, to the optimal timing of administration, and to the potential adverse effects need to be further clarified. Important insights will be hopefully provided soon by the several large multicenter investigations which are currently ongoing.

Postoperative costs associated with outcomes after cardiac surgery with extracorporeal circulation: role of antithrombin levels.

OBJECTIVE: To study the impact on postoperative costs of a patient's antithrombin levels associated with outcomes after cardiac surgery with extracorporeal circulation. DESIGN: An analytic decision model was designed to estimate costs and clinical outcomes after cardiac surgery in a typical patient with low antithrombin levels (<63.7%) compared with a patient with normal antithrombin levels (≥63.7%). The data used in the model were obtained from a literature review and subsequently validated by a panel of experts in cardiothoracic anesthesiology. SETTING: Multi-institutional (14 Spanish hospitals). PARTICIPANTS: Consultant anesthesiologists. MEASUREMENTS AND MAIN RESULTS: A sensitivity analysis of extreme scenarios was carried out to assess the impact of the major variables in the model results. The average cost per patient was €18,772 for a typical patient with low antithrombin levels and €13,881 for a typical patient with normal antithrombin levels. The difference in cost was due mainly to the longer hospital stay of a patient with low antithrombin levels compared with a patient with normal levels (13 v 10 days, respectively, representing a €4,596 higher cost) rather than to costs related to the management of postoperative complications (€215, mostly owing to transfusions). Sensitivity analysis showed a high variability range of approximately ±55% of the base case cost between the minimum and maximum scenarios, with the hospital stay contributing more significantly to the variation. CONCLUSIONS: Based on this analytic decision model, there could be a marked increase in the postoperative costs of patients with low antithrombin activity levels at the end of cardiac surgery, mainly ascribed to a longer hospitalization.

A price and use comparison of generic versus originator cardiovascular medicines: a hospital study in Chongqing, China.

BACKGROUND: Developed countries use generic competition to contain pharmaceutical expenditure. China, as a developing and transitional country, has not yet deemed an increase in the use of generic products as important; otherwise, much effort has been made to decrease the drug prices. This paper aims to explore dynamically the price and use comparison of generic and originator drugs in China, and estimate the potential savings of patients from switching originator drugs to generics. METHODS: A typical hospital in Chongqing, China, was selected to examine the price and use comparisons of 12 cardiovascular drugs from 2006 to 2011. RESULTS: The market share of the 12 generic medicines studied in this paper was 34.37% for volume and 31.33% for value in the second half of 2011. The price ratio of generic to originator drugs was between 0.34 and 0.98, and the volume price index of originators to generics was 1.63. The potential savings of patients from switching originator drugs to generics is 65%. CONCLUSION: The market share of the generics was lowering and the weighted mean price kept increasing in face of the strict price control. Under the background of hospitals both prescribing and dispensing medicines, China's comprehensive healthcare policy makers should take measures from supply and demand sides to promote the consumption of generic medicines.

The effect of the US Medicare Part D coverage gaps on medication use among patients with depression and heart failure.

BACKGROUND: Medication use among Medicare beneficiaries has increased and adherence has improved since the implementation of the Medicare Part D prescription drug benefit in 2006. However, the structure of the benefit, particularly, the coverage gap, is still problematic. It is critical to understand how beneficiaries with coexisting conditions respond to the coverage gap and whether their response differs by type of medications. AIMS OF THE STUDY: The paper aims to evaluate the effects of Medicare Part D's coverage gap on drug regimens among beneficiaries with coexisting depression and heart failure (HF). METHODS: Drug utilization patterns and medication adherence of a 5% random sample of Medicare Part D beneficiaries with depression and HF in 2007 were observed. Drug utilization patterns were measured on the basis of reported drug claims and medication adherence was defined as the proportion of days of medication possession in a given period. We compared pre-post drug use patterns and medication adherence across three groups: no coverage, generic coverage, and full coverage due to low-income subsidies (LIS) and used propensity score weighting to adjust for difference across groups. RESULTS: Beneficiaries with some drug coverage in the gap were more likely to enter the gap: 82% for LIS, 79% for generic-only and 58% for no coverage. Beneficiaries without drug coverage reduced their use of antidepressants by 5.0% (95% CI 1.7%-8.2%), and HF drugs by 9.4% (95% CI 7.2%-11.5%) after they entered the coverage gap. Those with generic coverage cut their brand-name drugs more than generic drugs but did not shift to generic drugs. However, adherence to antidepressants did not change; adherence to HF drugs reduced slightly, 2.5% (95% CI 1.2%-3.7%) in the no-coverage group and 2.6% (95% CI 1.3%-3.9%) in the generic-coverage group. CONCLUSIONS: The coverage gap was associated with a modest reduction in number of prescriptions filled for depression and HF but it was not associated with a significant effect on adherence. IMPLICATIONS FOR HEALTH POLICY: We found that beneficiaries with coexisting depression and HF were less likely to reduce their drug use than beneficiaries in general. In addition, the gap was not associated with a large reduction in adherence. It suggests that concerns about the coverage gap's harmful effects on medication adherence, or comorbidities might be overstated. IMPLICATIONS FOR FURTHER RESEARCH: Further studies on how people make medication use decisions in the face of changes in benefits and how the coverage affects non-drug medical outcomes are warranted.

Cost-effectiveness of levosimendan in patients with acute heart failure.

Heart failure is a major public health problem because of its high prevalence and impact on mortality, morbidity, quality of life, and social costs. The aim of this analysis was to estimate the effects of the novel inodilator levosimendan versus standard inotropic therapy (ST) of dobutamine in acute heart failure. A study population of 292 patients with acute heart failure was derived from an observational registry of patients referred to our department. Of these, 147 patients received iv levosimendan (0.05-0.1 µg·kg·min for 24 hours), and 145 patients were treated with ST. Duration of hospitalization, survival at 1 month, and the rehospitalization rate during the year after the index hospitalization were evaluated. Cost-effectiveness analysis was performed. The mean length of hospitalization was 12.08 and 13.57 days in the levosimendan and ST groups, respectively (P < 0.05). Rehospitalization rates were lower in the levosimendan group at 6 months (1.44% vs. 2.3%; P < 0.05) and 12 months (7.6% vs. 14.3%; P < 0.05). Mortality rate at 1 month was 2.1% versus 6.9% in the levosimendan and ST groups, respectively (P < 0.05). The per-capita cost of treatment with levosimendan was €78.86 higher than that with ST during the first hospitalization but €280.22 lower when the rehospitalization rate was considered.

Internet Marketing of Cardioprotective Dietary Supplements.

Objectives: Considering high prevalence of use of dietary supplements and their easy access on the internet, the aim of this research was to examine and assess the prevalence of the internet marketing of heart-protective supplements as the most popular supplements of today, and to investigate the quality and quantity of information that are available to consumers on the sale websites. Design: Three major search engines (Google, Yahoo, and Bing) and keywords "cardiovascular supportive supplements online buy" were used to identify websites that sell cardioprotective dietary supplements. Content of first 50 listed websites in each engine was evaluated for its compliance with regulatory acts while information about supplements' efficacy and safety was compared with the results of the latest scientific research. Results: Of a total of 150 listed websites, 89 selling supplements for the specific indication underwent further analysis. The most commonly registered cardioprotective dietary supplements on the internet were supplements based on omega-3 fatty acids (omega-3) (57 websites, 64.05%). Related to the websites selling omega-3 supplements, risk reduction claims were presented at 23 (40.35%), whereas structure or function claims were present at 50 (87.72%) analyzed websites, but followed with Food and Drug Administration disclaimer only on 68.00% of them. Information about adverse effects were rarely pointed out (1 website, 1.75%) unlike warnings, which were significantly more available to consumers (38, 66.67%). Conclusions: According to obtained results, most of the analyzed websites that sell omega-3 supplements did not contain all important medical information required by Dietary Supplement Health and Education Act. Since use of internet marketing is in expansion and since consumers have no access to relevant medical information about dietary supplements on the selling websites, there is a clear need for better quality control of websites and greater public awareness of these widely used products.

Economic analysis of intermittent intravenous outpatient treatment with levosimendan in advanced heart failure in Spain.

INTRODUCTION AND OBJECTIVES: Advanced heart failure (HF) leads to high hospitalization and mortality rates. The LION-HEART study was a randomized, placebo-controlled clinical trial that evaluated the safety and efficacy of intravenous administration of intermittent doses of levosimendan in outpatients with advanced HF. The aim of the present study was to perform a cost analysis to determine whether the lower rate of hospitalizations for HF, observed in patients treated with levosimendan in the LION-HEART study, can generate savings for the Spanish national health system compared with the option of not treating patients with advanced HF. METHODS: An economic model was used that included IC hospitalization rates from the LION-HEART study, the costs of hospitalization due to HF and those of the acquisition and intravenous administration of levosimendan. The time horizon of the analysis was 12 months. Two analyses were carried out, one deterministic and the other probabilistic (second-order Monte Carlo simulation). RESULTS: In the deterministic analysis, the total saving for each patient treated with levosimendan would amount to-€698.48. In the probabilistic analysis, the saving per patient treated with levosimendan would be-€849.94 (95%CI, €133.12 to-€2,255.31). The probability of savings with levosimendan compared with the no treatment option would be 94.8%. CONCLUSIONS: Intermittent ambulatory treatment with levosimendan can generate savings for the Spanish national health system compared with the option of not treating patients with advanced HF.

Levosimendan in patients with reduced left ventricular function undergoing isolated coronary or valve surgery.

OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS: Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.

[Economic assessment of dexrazoxane in prophylaxis of cardiotoxicity in children undergoing chemotherapy with anthracyclines]. / Avaliação econômica do uso de dexrazoxano na profilaxia de cardiotoxicidade em crianças em tratamento quimioterápico com antraciclinas.

Cancer in individuals 0 to 19 years of age is considered rare when compared to incidence in older age brackets, and is estimated at 2% to 3% of all malignant tumors recorded in Brazil. The use of anthracyclines is frequently associated with cardiotoxicity, and these drugs are part of approximately 60% of treatment protocols in pediatric oncology. Among the existing strategies for the prevention of cardiotoxicity, dexrazoxane obtained favorable results based on intermediate outcomes (biochemical markers and echocardiographic parameters). This study was based on a cost-effectiveness assessment comparing the use of dexrazoxane in different populations, besides an assessment of the budget impact from the technology's potential incorporation. The patient's lifetime was used as the timeline, and the analysis was performed from the perspective of the Brazilian Unified National Health System (SUS). A budget impact analysis was also performed for each technology. After a literature search, a Markov model was developed, capable of comparing the use of dexrazoxane in six profiles of patients at risk of developing cardiotoxicity. Use of the drug in children under 5 years of age proved to be the most cost-effective alternative (incremental cost effectiveness ratio - ICER of BRL 6,156.96), followed by use in all patients (ICER of BRL 58,968.70). If the price decreased to less than BRL 250.00 per vial, the alternative of using the drug in all children would become the most cost-effective. The budget impact at 5 years was BRL 30,622,404.81 for use only in children under 5 years of age. Using the technology in all the children could produce an incremental impact of BRL 94,352,898.77.

O câncer em indivíduos de 0 a 19 anos é considerado raro, quando comparado à incidência em faixas etárias maiores, sendo estimado entre 2% e 3% de todos os tumores malignos registrados no Brasil. O uso de antraciclinas está frequentemente associado ao aparecimento de cardiotoxicidade e faz parte de aproximadamente 60% dos protocolos terapêuticos em oncologia pediátrica. Dentre as estratégias existentes para a prevenção de cardiotoxicidade, o dexrazoxano obteve resultados favoráveis pautados em desfechos intermediários (marcadores bioquímicos e medidas ecocardiográficas). Foi desenvolvida, neste trabalho, uma avaliação de custo-efetividade que compare o uso do dexrazoxano em diferentes populações, além de uma avaliação do impacto orçamentário causado pela possível incorporação da tecnologia. Foi utilizado o horizonte temporal de toda a vida do paciente e a perspectiva de análise do Sistema Único de Saúde. Uma análise de impacto orçamentário para cada tecnologia também foi construída. Após uma busca na literatura, foi desenvolvido um modelo de Markov capaz de comparar o uso do dexrazoxano em seis perfis de pacientes com risco de desenvolver cardiotoxicidade. Usar o medicamento nas crianças menores de cinco anos de idade se mostrou a alternativa mais custo-efetiva (razão de custo-efetividade incremental - RCEI de R$ 6.156,96), seguida de usar em todos os pacientes (RCEI de R$ 58.968,70). Caso o preço diminua a um valor menor que R$ 250,00 por frasco, a alternativa de usar em todas as crianças se torna a mais custo-efetiva. O impacto orçamentário ao final de cinco anos foi de R$ 30.622.404,81 para uso apenas nas crianças menores de cinco anos. Usar a tecnologia em todas as crianças produziria um impacto incremental de R$ 94.352.898,77.

El cáncer en individuos de 0 a 19 años está considerado raro, cuando se compara la incidencia en franjas etarias mayores, estimándose entre 2% y 3% de todos los tumores malignos registrados en Brasil. El uso antraciclinas está frecuentemente asociado a la aparición de cardiotoxicidad y forma parte de aproximadamente un 60% de los protocolos terapéuticos en oncología pediátrica. Entre las estrategias existentes para la prevención de cardiotoxicidad, el dexrazoxano obtuvo resultados favorables pautados en desenlaces intermedios (marcadores bioquímicos y medidas ecocardiográficas). Se desarrolló en este trabajo, una evaluación de costo efectividad que compare el uso del dexrazoxano en diferentes poblaciones, además de una evaluación del impacto presupuestario causado por la posible incorporación de la tecnología. Se utilizó el horizonte temporal de toda la vida del paciente y la perspectiva de análisis del SUS. También se realizó un análisis del impacto presupuestario para cada tecnología. Tras una búsqueda en la literatura, se desarrolló un modelo de Markov capaz de comparar el uso del dexrazoxano en 6 perfiles de pacientes con riesgo de desarrollar cardiotoxicidad. Usar el medicamento en los niños menores de 5 años de edad se mostró la alternativa más costo-efectiva (relación costo-efectividad incremental - RCEI de BRL 6.156,96), seguido de usarlo en todos los pacientes (RCEI de BRL 58.968,7). En caso de que el precio disminuya a un valor inferior a BRL 250,00 por frasco, la alternativa de usarlo en todos los niños se convierte en la más costo-efectiva. El impacto presupuestario tras 5 años fue de BRL 30.622.404,81 para su uso exclusivo en niños menores de 5 años. Usar esta tecnología en todos los niños, tendría un impacto presupuestario incrementándolo hasta los BRL 94.352.898,77.

Comparison of the initial hospitalization costs between the patients treated with dobutamine and the patients treated with amrinone for acute decompensated heart failure in a Japanese institute.

OBJECTIVES: Phosphodiesterase (PDE) III inhibitor therapy is effective for treatment of acute decompensated heart failure (ADHF). Nevertheless, this drug is expensive than conventional inotropic agent dobutamine. We compared total medication costs of the patients treated with PDE III inhibitor amrinone therapy to that of the patients treated with conventional dobutamine therapy during initial hospitalization. METHODS: We analyzed 160 consecutive patients with ADHF admitted to our hospital. Shock, dehydration, severe infection, multiple organ failure, and mild heart failure (New York Heart Association class IIs) were not eligible for the study. Ninety-seven patients were divided into two groups: 1) DOB group treated with dobutamine therapy; and 2) AMR group treated with amrinone therapy. Total medication costs and cost for hospital room charge were calculated based on their usage during the initial hospitalization for each patient. Group comparison was done between the DOB and AMR groups. RESULTS: Length of stay was longer in the DOB group than in the AMR group. Mean calculated cost of intravenous drugs was higher in the DOB group (173,186 +/- 239,147 yen) than in the AMR group (63,145 +/- 47,223 yen, P < 0.05). Total medication costs were higher in the DOB group than in the AMR group. Cost for hospital room charge was higher in the DOB group than in the AMR group. CONCLUSIONS: In the treatment of ADHF, appropriate therapy even with expensive drugs makes total medication costs less expensive comparing with conventional therapy with cheaper drugs during initial hospitalization.

Oral midodrine is effective for the treatment of hypotension associated with carotid artery stenting.

Hypotension is commonly encountered during carotid artery stenting (CAS), mediated by vagal stimulation and suppression of sympathetic outflow. Some patients require treatment with intravenous vasopressors (dopamine, nor-epinephrine, or phenylephrine). The authors describe the successful use of the oral agent midodrine as an alternative to intravenous vasopressors in the treatment of hypotension related to CAS. Of 55 patients who underwent elective CAS, 19 (35%) experienced significant hypotension, and 15 (27%) required vasopressor therapy. Eleven patients received intravenous dopamine infusion in an intensive care setting, whereas 4 received oral midodrine in a regular telemetry unit. All patients eventually recovered and were discharged without any residual cardiovascular or neurological complications. No major side effects were noted with the use of both dopamine and midodrine. Cost of hospitalization was significantly higher in the dopamine group because of the need for ICU admission.

The costs of treating acute heart failure: an economic analysis of the SURVIVE trial.

OBJECTIVE: To estimate the incremental cost per life year gained with levosimendan relative to dobutamine in treatment of acute heart failure based on the Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) trial. METHODS: SURVIVE enrolled 1,327 patients (levosimendan 664, dobutamine 663) from nine nations with 180-day survival from date of randomisation as the primary endpoint. Hospital resource utilisation was determined via clinical case reports. Unit costs were derived from hospital payment schedules for France, Germany and the UK, and represent a third-party payer perspective. Cost-effectiveness analysis was performed for a subset of the SURVIVE patient population selected in accordance with current levosimendan labeling. RESULTS: Mortality in the levosimendan group was 26 versus 28% for dobutamine (hazard ratio 0.91, 95% confidence interval 0.74-1.13, p=0.40). Initial hospitalisation length of stay was identical (levosimendan 14.4, dobutamine 14.5, p=0.98). Slightly lower rates of readmission were observed for levosimendan relative to dobutamine at 31 (p=0.13) and 180 days (p=0.23). Mean costs excluding study drug were equivalent for the index admission (levosimendan euro5,060, dobutamine euro4,952; p=0.91) and complete episode (levosimendan euro5,396, dobutamine euro5,275; p=0.93). CONCLUSION: At an acquisition cost of euro600 per vial, there is at least 50% likelihood that levosimendan is cost effective relative to dobutamine if willingness to pay is equal to or greater than euro15,000 per life year gained.

Continuous Cardiac Inotropes in Patients With End-Stage Heart Failure: An Evolving Experience.

Heart failure (HF) experts recommend initiation of continuous inotrope therapy, such as milrinone or dobutamine, for clinically decompensating patients with stage D HF. Although originally intended to serve solely as a bridge to more definitive surgical therapies, more and more patients are receiving inotrope therapy for purely palliative purposes. In these cases, questions arise regarding care at the end of life. What criteria determine ongoing clinical benefit? Should the inotrope be continued until death? Should inotrope dosing be increased within recommended guidelines to improve symptoms? What is the role of inotropes in hospice care? Here, we describe such a case as a springboard to contemplate the evolving role of inotrope therapies and how hospice and palliative providers may interface with this rapidly developing face of advanced HF care.

Cost-Effectiveness of Left Ventricular Assist Devices in Ambulatory Patients With Advanced Heart Failure.

OBJECTIVES: This study assessed the cost-effectiveness of left ventricular assist devices (LVADs) as destination therapy in ambulatory patients with advanced heart failure. BACKGROUND: LVADs improve survival and quality of life in inotrope-dependent heart failure, but data are limited as to their value in less severely ill patients. METHODS: We determined costs of care among Medicare beneficiaries before and after LVAD implantation from 2009 to 2010. We used these costs and efficacy data from published studies in a Markov model to project the incremental cost-effectiveness ratio (ICER) of destination LVAD therapy compared with that of medical management. We discounted costs and benefits at 3% annually and report costs as 2016 U.S. dollars. RESULTS: The mean cost of LVAD implantation was $175,420. The mean cost of readmission was lower before LVAD than after ($12,377 vs. $19,465, respectively; p < 0.001), while monthly outpatient costs were similar ($3,364 vs. $2,974, respectively; p = 0.54). In the lifetime simulation model, LVAD increased quality-adjusted life-years (QALYs) (4.41 vs. 2.67, respectively), readmissions (13.03 vs. 6.35, respectively), and costs ($726,200 vs. $361,800, respectively) compared with medical management, yielding an ICER of $209,400 per QALY gained and $597,400 per life-year gained. These results were sensitive to LVAD readmission rates and outpatient care costs; the ICER would be $86,900 if these parameters were 50% lower. CONCLUSIONS: LVADs in non-inotrope-dependent heart failure patients improved quality of life but substantially increased lifetime costs because of frequent readmissions and costly follow-up care. LVADs may provide good value if outpatient costs and adverse events can be reduced.

Chronic inotropic therapy in end-stage heart failure.

BACKGROUND: Interventions in advanced heart failure that provide symptom relief and decrease hospital readmission are important. Chronic intravenous inotropic therapy represents a pharmacologic approach that has been advocated for palliative treatment. However, little is known about associated mortality and cost. Therefore, we sought to describe the impact of chronic infusions on resource use and survival. METHODS: Data were reviewed for a 17-state Medicare region from 1995 to 2002. We obtained hospital and outpatient expenditures accrued up to 180 days before and after the initiation of chronic infusions. Health care use was defined by dollars reimbursed for drug and hospitalizations per beneficiary. Average accumulated cost curves were generated for dollars reimbursed for drug and for hospitalizations by days at risk. RESULTS: The mean age of the cohort (n = 331) was 69.1 +/- 11.3 years. Mortality exceeded 40% at 6 months. Reductions in hospital days were observed at all time points. The amounts reimbursed at 30 and 60 days before and after initiation of inotrope favor drug therapy; however, at six months, the amounts reimbursed were greater due to the cost of milrinone. CONCLUSIONS: Chronic intravenous inotrope use was associated with a high mortality. The cost for milrinone was significant, but there was a decrease in expenditures for subsequent hospitalizations. In the absence of appropriately designed clinical trials, the data suggest that the decision to use inotropes, the choice of inotrope, and the duration of treatment should reflect the impact on resource use.

Drug utilization pattern in the intensive care unit of a tertiary care hospital.

The authors studied the factors affecting drug use pattern, cost of therapy, and the association between the pattern of drug use and survival as well as the duration of stay in a prospective, observational study in an intensive care unit between February and May 2005. Data were collected regarding drugs used, severity of the disease, and their outcome. The mean +/- SD of the Acute Physiology and Chronic Health Evaluation (APACHE III) and Glasgow Coma Scale (GCS) scores of 84 patients were 52.2 +/- 19.4 and 7.5 +/- 2.4, respectively. Although the mean number of drugs at the time of admission to the intensive care unit was 5.3, it increased to 12.9 on the first day and 22.2 during the entire stay. More than 50% of the average expenditure on drugs and nutrition was accounted by antibiotics. Requirement of insulin or inotropes signified an adverse outcome on mortality (odds ratios of 3.43 and 8.44, respectively). In conclusion, there is a tremendous impact of antibiotic use on the cost of therapy in the intensive care unit. The requirement of certain drugs such as insulin and inotropes is of prognostic significance.

Outcomes associated with vasoactive therapy in patients with acute decompensated heart failure.

STUDY OBJECTIVES: To describe the clinical management of acute decompensated heart failure (ADHF) in patients receiving intravenous treatment with dobutamine, milrinone, or nesiritide, and to evaluate differences, based on treatment received, in the in-hospital mortality rate, length of stay (LOS), total health care costs, and 30-day hospital readmission rate. DESIGN: Retrospective cohort analysis. DATA SOURCE: University HealthSystem Consortium (UHC) Clinical Database Pharmacy, a database with information from 32 academic hospitals. PATIENTS: Two thousand one hundred thirty patients with ADHF who received dobutamine (1311 patients), milrinone (433), or nesiritide (386). MEASUREMENTS AND MAIN RESULTS: Patients with ADHF were categorized according to the vasoactive therapy received. To evaluate baseline characteristics, chi(2) analysis was used; logistic regression was employed to assess the relationships between drug therapy and in-hospital mortality rates, and multivariate linear regression was used to assess whether drug therapy was related to LOS and total health care costs. All regression analyses controlled for age, sex, race, region of the United States where the hospital was located, primary payer for the hospital stay, UHC patient severity class, and chronic renal failure. In-hospital mortality rates were 10.2%, 7.9%, and 2.9% in the dobutamine, milrinone, and nesiritide groups, respectively. This resulted in an adjusted odds ratio for death of 3.5 (95% confidence interval [CI] 1.8-6.8) for dobutamine and 3.9 (95% CI 1.8-8.3) for milrinone (p<0.0001). Compared with inotropic therapy (dobutamine and milrinone), mean LOS in the hospital and the intensive care unit were lower with nesiritide (p<0.001). Total health care costs were lowest with nesiritide, but this reached statistical significance only when compared with milrinone (p<0.001). Thirty-day hospital readmission rates with dobutamine, milrinone, and nesiritide were 5.0%, 9.5%, and 3.9%, respectively (p=NS). CONCLUSION: Nesiritide therapy was associated with a lower in-hospital mortality rate and shorter LOS compared with dobutamine and milrinone. In addition, total health care costs with nesiritide were decreased compared with milrinone. These observations need to be validated by a randomized controlled trial.

Pharmacoeconomic modeling of nesiritide versus dobutamine for decompensated heart failure.

STUDY OBJECTIVE: To model the cost-effectiveness of nesiritide compared with dobutamine in patients with decompensated heart failure. DESIGN: Cost-effectiveness analysis. MEASUREMENTS AND MAIN RESULTS: A decision tree model was derived from randomized clinical trial data and data from a previously published economic study. Four cost-effectiveness analyses were performed: analysis 1 -- full probabilistic analysis, repeatedly sampled probabilities for 6-month mortality and hospital readmission from distributions based on 95% confidence intervals (CIs); analysis 2 -- best-case nesiritide analysis, used the limiting values of the 95% CI favorable to nesiritide; analysis 3 -- best-case dobutamine analysis, used the limiting values of the 95% CI favorable to dobutamine; and analysis 4 -- replicated the previously published cost-effectiveness study and served as a methodologic control. Fifty-one consecutive Monte Carlo simulations for cohorts of 1000 hypothetical patients were performed for each analysis. Incremental cost, incremental effectiveness, and incremental cost-effectiveness ratios (ICERs) were calculated for nesiritide versus dobutamine. Analysis 1 showed a mean ICER of 767 US dollars/life-year gained for nesiritide versus dobutamine (incremental cost 251 US dollars +/- 290 US dollars, incremental effectiveness 0.33 +/- 0.22 yr). The 95% confidence region surrounding this point estimate spanned all four quadrants of the incremental cost-effectiveness scatterplot, suggesting inconclusive results. Nesiritide was the dominant treatment strategy in analysis 2 (incremental cost -734 US dollars+/- 106 US dollars, incremental effectiveness 1.19 +/- 0.07 yrs), whereas dobutamine was dominant in analysis 3 (incremental cost 1242 +/- 73 US dollars, incremental effectiveness -0.57 +/- 0.05 yr). Analysis 4 was comparable to the previously published cost-effectiveness analysis (incremental cost -77 +/- 87 US dollars, incremental effectiveness 0.48 +/- 0.05 yr). CONCLUSIONS: Based on available randomized clinical trial data, nesiritide did not exhibit robust economic superiority over dobutamine. When incorporating the uncertainty (i.e., 95% CIs) in clinical effectiveness as reported in available clinical trial data into the economic analysis, either nesiritide or dobutamine may be the dominant treatment (i.e., more effective at lower cost) for the studied population. Economic analyses of nesiritide and any comparator must account for uncertainty in estimates of cost as well as in clinical effectiveness.