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.

Cost effectiveness of cardiac resynchronization therapy in the Nordic region: an analysis based on the CARE-HF trial.

BACKGROUND: The aim of this study was to investigate the cost-effectiveness of cardiac resynchronization therapy (CRT) in Denmark, Finland and Sweden. The analysis was based on the CARE-HF trial, a randomised clinical trial investigating the efficacy of adding CRT (n=409) to optimal pharmacological treatment (n=404) in patients with moderate to severe heart failure with markers of cardiac dyssynchrony. The average follow-up time was 29.4 months. METHODS: The health effects were measured in terms of quality-adjusted life years (QALYs) gained. Data on health care resource consumption from CARE-HF was combined with costs for CRT implantation and hospitalisation from university hospitals in Denmark, Finland and Sweden. Calculations were based on patients' expected life time. The expected device lifetime (6 years) was used for CRT, and no additional gains in clinical effects were assumed after the 6 years. RESULTS: The cost-effectiveness ratio per QALY gained was 4800 euros in Denmark, 3600 euros in Finland and 6700 euros in Sweden. The 95% confidence intervals for the cost per QALY gained varied between a lower limit of 1169 euros in Finland to an upper limit of 17,482 euros in Sweden. These values were all below the threshold for being cost-effective in Denmark, Finland and Sweden. CONCLUSIONS: The study indicates that CRT is a cost-effective treatment in Scandinavian health care settings compared to traditional pharmacological therapy and can therefore be recommended for routine use in patients with moderate to severe heart failure and markers of dyssynchrony.

Pre-conditioning activates adenosine utilization in a cost-effective way during myocardial ischaemia.

During pre-conditioning the interstitial concentration of adenosine, in contrast to lactate, presents a die-away curve-pattern for every successive episode of ischaemia. This die-away pattern might not necessarily be attributed to diminished adenosine production. The present study was undertaken to investigate whether pre-conditioning alters the metabolic turnover of adenosine as observed by the lactate production during ischaemia. Interstitial levels of metabolites in pre-conditioned (n=21) and non-preconditioned (n=21) porcine hearts were monitored with microdialysis probes inserted in both ischaemic and non-ischaemic tissue in an open chest heart model. Three subgroups perturbated with either plain microdialysis buffer (control), buffer containing adenosine (375 microM), or buffer containing deoxyadenosine (375 microM) were studied. All animals were subjected to 90 min of equilibrium microdialysis before 40 min of regional myocardial ischaemia and 120 min of reperfusion. Pre-conditioning consisted of four repetitive episodes of 10 min of ischaemia and 20 min of reperfusion. Significantly higher levels of inosine and lactate were found in the ischaemic tissue of the pre-conditioned subgroup receiving adenosine (P < 0.05) compared with the other two subgroups receiving deoxyadenosine and plain buffer, respectively. This difference was only valid for pre-conditioned ischaemic myocardium, and hence equal amounts of inosine and lactate were produced in the non-preconditioned ischaemic myocardium regardless of the presence of adenosine or deoxyadenosine. In the non-ischaemic myocardium baseline levels of metabolites were measured in all subgroups. Pre-conditioning favoured degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the pre-conditioned ischaemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5'-triphosphate (ATP) investment. Utilization of adenosine in this way may also explain the successive die-away pattern of adenosine seen in consecutive pre-conditioning cycles.