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: 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.

Cost-benefits of incorporating levosimendan into cardiac surgery practice: German base case.

OBJECTIVE: To evaluate the cost-benefit of using levosimendan compared with dobutamine, in the perioperative treatment of patients undergoing cardiac surgery who require inotropic support. METHODS: A two-part Markov model was designed to simulate health-state transitions of patients undergoing cardiac surgery, and estimate the short- and long-term health benefits of treatment. Hospital length of stay (LOS), mortality, medication, and adverse events were key clinical- and cost-inputs. Cost-benefits were evaluated in terms of costs and bed stays within the German healthcare system. Drug prices were calculated from the German Drug Directory (€/2014) and published literature, with a 3% annual discount rate applied. The base case analysis was for a 1-year time horizon. RESULTS: The use of levosimendan vs dobutamine was associated with cost savings of €4787 per patient from the German hospital perspective due to reduced adverse events and shorter hospital LOS, leading to increased bed capacity and hospital revenue. LIMITATIONS: A pharmacoeconomic calculation for the specific situation of the German healthcare system that is based on international clinical trial carries a substantial risk of disregarding potentially relevant but unknown confounding factors (i.e., ICU-staffing, co-medications, standard-ICU care vs fast-tracking, etc.) that may either attenuate or increase the outcome pharmacoeconomic effects of a drug; however, since these conditions would also apply for patients treated with comparators, their net effects may not necessarily influence the conclusions. CONCLUSIONS: The use of levosimendan in patients undergoing cardiac surgery who require inotropic support appears to be cost-saving. The results of the analysis provide a strong rationale to run local clinical studies with pharmacoeconomic end-points which would allow a much more precise computation of the benefits of levosimendan.

Pharmaco-economics of levosimendan in cardiology: a European perspective.

INTRODUCTION: Heart failure places a significant economic burden on health care. Acute heart failure requires hospitalization and often frequent re-hospitalization in expensive wards where vasoactive rescue therapy is often added on top of standard medications. In these lean times, there is a growing need for cost-effective therapeutic options that supply superior support and in addition shorten the length of stay in hospital and reduce re-hospitalization rates. The inodilator levosimendan represents the latest addition to the vasoactive treatments of acute heart failure patients, and it appears to meet these expectations. Our aim was to answer the question whether the treatment efficacy of levosimendan - when selected as therapy for patients hospitalized for acute heart failure - brings savings to hospitals in various European countries representing different economies. METHODS AND RESULTS: We took a conservative approach and selected some a fortiori arguments to simplify the calculations. We selected seven European countries to represent different economies: Italy, Spain, Greece, Germany, Sweden, Finland and Israel. Data on the costs of medications and on the cost per day were collected and fed in a simple algorithm to detect savings. These saving varied from country to country, from a minimum of €0.50 in Germany to a maximum of €354.64 in Sweden. CONCLUSIONS: The use of levosimendan as a therapy for patients hospitalized for acute heart failure provides a net saving to hospitals driven by a reduction in the length of hospital stay. This finding is true in each of the countries considered in this study.

Economic evaluation of levosimendan versus dobutamine for the treatment of acute heart failure in Italy.

INTRODUCTION: Inodilators are the first-choice class of drugs for the treatment of acute heart failure (AHF). Levosimendan is a relatively recent inodilatory agent, presenting superior outcomes in comparison with traditional inotropes. METHODS: An economic evaluation of levosimendan for the treatment of AHF in Italy was performed. In a retrospective study conducted on patients with AHF admitted to a teaching hospital in Rome, two groups were derived from an observational registry: 147 patients treated with levosimendan and 145 treated with dobutamine. Follow-up was at 1 year after treatment. In the reference study looked at in this paper, treatment with levosimendan reduced mean length of stay (LOS) by 1.5 days (P<0.05). Reduction in the rehospitalization rate was 6.7% (P<0.05). Mortality rate at 1 month was reduced by 4.8% (P<0.05). RESULTS: Based on the reference study, a cost analysis from the hospital perspective was carried out. The incremental cost of treatment with levosimendan (€697) was equivalent to the incremental savings (€694), the latter being obtained from the reduction in LOS (€508) and rehospitalization rate (€186). CONCLUSION: Despite the limitations of this study, and even neglecting all nonmonetary health gains as additional outcomes, levosimendan appears to be a competitive alternative compared with dobutamine for the treatment of AHF in the Italian hospital setting.

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.

Hospital costs for treatment of acute heart failure: economic analysis of the REVIVE II study.

BACKGROUND: Acute heart failure (AHF) is the leading cause of hospital admission among older Americans. The Randomized EValuation of Intravenous Levosimendan Efficacy (REVIVE II) trial compared patients randomly assigned to a single infusion of levosimendan (levo) or placebo (SOC), each in addition to local standard treatments for AHF. We report an economic analysis of REVIVE II from the hospital perspective. METHODS: REVIVE II enrolled patients (N = 600) hospitalized for treatment of acute decompensated heart failure (ADHF) who remained dyspneic at rest despite treatment with intravenous diuretics. Case report forms documented index hospital treatment (drug administration, procedures, days of treatment by care unit), as well as subsequent hospital and emergency department admissions during follow-up ending 90 days from date of randomization. These data were used to impute cost of admission based on an econometric cost function derived from >100,000 ADHF hospital billing records selected per REVIVE II inclusion criteria. RESULTS: Index admission mean length of stay (LOS) was shorter for the levo group compared with standard of care (SOC) (7.03 vs 8.96 days, P = 0.008) although intensive care unit (ICU)/cardiac care unit (CCU) days were similar (levo 2.88, SOC 3.22, P = 0.63). Excluding cost for levo, predicted mean (median) cost for the index admission was levo US $13,590 (9,458), SOC $19,021 (10,692) with a difference of $5,431 (1,234) favoring levo (P = 0.04). During follow-up through end of study day 90, no significant differences were observed in numbers of hospital admissions (P = 0.67), inpatient days (P = 0.81) or emergency department visits (P = 0.41). Cost-effectiveness was performed with a REVIVE-II sub-set conforming to current labeling, which excluded patients with low baseline blood pressure. Assuming an average price for levo in countries where currently approved, there was better than 50% likelihood that levo was both cost-saving and improved survival. Likelihood that levo would be cost-effective for willingness-to-pay below $50,000 per year of life gained was about 65%. CONCLUSIONS: In the REVIVE II trial, patients treated with levo had shorter LOS and lower cost for the initial hospital admission relative to patients treated with SOC. Based on sub-group analysis of patients administered per the current label, levo appears cost-effective relative to SOC.

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.

[Cost analysis of the treatment of acute decompensated heart failure. Levosimendan versus dobutamine]. / Análise de custos do tratamento de episódios de descompensação aguda de insuficiência cardíaca. Levosimendan versus dobutamina.

OBJECTIVE: To assess whether the treatment with levosimendan is more expensive than the usual one with dobutamine, since price of medications does not usually represent the greatest expense in the treatment of cardiac decompensation. METHODS: The cost of treatment of 18 inpatients with cardiac decompensation, 9 of which treated with dobutamine (dobuta group) and 9 with levosimendan (levo group), was compared. Groups were similar concerning age, sex, functional class and cardiac function. RESULTS: Treatment costs were similar for both groups. In the levo group, the costs with the drug were higher than in the dobuta group, but those related to the length of stay in intensive care unit and to the material used during admission were lower. Levo-drug: R$ 5,414.00; material: R$ 399.90; hospital daily rates: R$ 5,061.20; professional honorarium: R$ 3,241.80; total costs: R$ 14,117.00. Dobuta-drug: R$ 2,320.10; materials: R$ 1,665.70; hospital daily rates: R$ 6,261.90; professional honorarium: R$ 3,894.30; total costs: R$ 14,142.00. CONCLUSION: Despite the higher price of levosimendan, the global cost of the treatment was similar for patients who were treated either with dobutamine or levosimendan. Patients who were treated with levosimendan had a shorter length of stay in intensive care unit.

Análise de custos do tratamento de episódios de descompensacão aguda de insuficiência cardíaca: levosimendan versus dobutamina / Cost analysis of the treatment of acute decompensated heart failure: levosimendan versus dobutamine

OBJETIVO: Verificar se o tratamento com levosimendan seria mais dispendioso que o usual com dobutamina, uma vez que o preco dos medicamentos não representa a maior despesa no tratamento da descompensacão cardíaca. MÉTODOS: Comparou-se o custo do tratamento de 18 pacientes hospitalizados devido a descompensacão cardíaca, 9 tratados com dobutamina (grupo dobuta) e 9 com levosimendan (grupo levo). Os grupos foram semelhantes quanto à idade, sexo, classe funcional e funcão cardíaca. RESULTADOS: O custo do tratamento foi semelhante para os dois grupos. No grupo levo as despesas com medicamentos foram maiores, mas as relativas ao período de terapia intensiva e do material empregado foram menores. Levo - medicamentos: R$ 5.414,00; materiais: R$ 399,90; diárias hospitalares: R$ 5.061,20; servicos profissionais: R$ 3.241,80; final: R$ 14.117,00. Dobuta - medicamentos: R$ 2.320,10; materiais: R$ 1.665,70; diárias hospitalares: R$ 6.261,90; servicos profissionais: R$ 3.894,30; final: R$ 14.142,00. CONCLUSAO: Apesar do preco mais elevado da droga, o custo global do tratamento foi semelhante para os pacientes tratados com dobutamina ou levosimendan. O paciente tratado com levosimendan permaneceu menos tempo em terapia intensiva.

Intravenous levosimendan treatment is cost-effective compared with dobutamine in severe low-output heart failure: an analysis based on the international LIDO trial.

BACKGROUND: Levosimendan, a novel calcium sensitiser, improves cardiac performance and symptoms without increasing oxygen consumption, and decreases the mortality of patients with low-output heart failure. AIMS: To estimate the cost-effectiveness of intravenous treatment with levosimendan compared with dobutamine in patients with severe low-output heart failure. METHODS: This economic evaluation was based on a European clinical trial (LIDO), in which 203 patients with severe heart failure randomly received a 24 h infusion with either levosimendan or dobutamine. Survival and resource utilisation data were collected for 6 months; survival was extrapolated assuming a mean additional lifetime of 3 years based on data from the Cooperative North Scandinavian Enalapril Survival Study trial. Costs were based on study drug usage and hospitalisation in the 6-month follow-up. A sensitivity analysis on dosage of drug and duration of survival was performed. RESULTS: The mean survival over 6 months was 157+/-52 days in the levosimendan group and 139+/-64 days in the dobutamine group (P<0.01). When extrapolated up to 3 years, the gain in life expectancy was estimated at 0.35 years (discounted at 3%). Levosimendan increased the mean cost per patient by 1108, which was entirely due to the cost of the study drug. The incremental cost per life-year saved (LYS) was 3205 at the European level; in the individual countries the cost per LYS ranged between 3091 and 3331. The result was robust in the sensitivity analysis. CONCLUSIONS: Although the patients in the levosimendan group were alive for more days and thus at risk of hospitalisation for longer, there was no increase in hospitalisation or hospitalisation costs with levosimendan treatment. The cost per LYS using levosimendan compares favourably with other cost-effectiveness analyses in cardiology.