Use of levosimendan versus dobutamine when inotropic support is needed in patients with severe acute decompensated chronic heart failure

Abstract

The aim – to conduct clinical effectiveness, meta-analysis of 30 and 120-days mortality data, pharmacoeconomic evaluation of levosimendan treatment compared with dobutamine in patients with severe acute decompensated chronic heart failure (ADCHF) who require inotropic support. Materials and methods. The PubMed and Cochrane databases were searched for direct randomized clinical trials of levosimendan treatment compared with dobutamine in patients with ADCHF. The clinical efficacy of levosimendan and dobutamine was analyzed. Pharmacoeconomic analysis was carried out using the cost-effectiveness method with an assessment of the incremental cost-effectiveness ratio. A decision tree model of levosimendan or dobutamine treatments was constructed. The efficacy endpoints and impact on the budget were analyzed in terms of long-term effectiveness of levosimendan and dobutamine use. Discounted was conducted with rate of 3 %. Sensitivity analysis was carried out in terms of price changing of drugs, the cost of drugs in mg, the likelihood of re-hospitalization of the patient in a 3-year horizon and survival in the long term.Results and discussion. Analysis of clinical data and meta-analysis of randomized clinical trials found that mortality rates with levosimendan and dobutamine in the 30-day period were 9.6 % and 13.8 %, RR 0.71 (95 % CI 0.53–0.95) and in the 120-day period – 13.5 % and 25.2 %, RR 0.54 (95 % CI 0.32–0.92), respectively. The total cost of the course of treatment, taking into account the price of the drug, medical devices, staff services, diagnostic procedures and treatment of adverse reactions when using levosimendan, was 34 003.02 UAH per patient and 18 787.28 UAH when treated with dobutamine. The weighted average hospital stay was 6.4 days in case of levosimendan treatment and 7.5 days of dobutamine treatment. Extrapolation of the data from clinical trials to the 3-year survival rate of patients allowed us to determine an additional indicator of efficacy – the number of life years saved with levosimendan – 2.64 and 2.37 with dobutamine treatment. A cost-effectiveness analysis found that levosimendan is more efficient but more expensive technology compare to dobutamine. The incremental cost-effectiveness ratio for the additional life year saved of a patient with severe CHF is 43,473.55 UAH, which is 6 times less than the likely threshold of willingness to pay in Ukraine.Conclusions. The multivariate sensitivity analysis detected the model sustainability to the most crucial parameters of the model – drug price; the cost of drugs associated with their actual use in mg, the possibility of re-hospitalization of the patient in a 3-year horizon, and long-term survival, which is associated with the time horizon of the model. The total cost of a cohort of patients with ADCHF in Ukraine when using scenario 1 (100 % distribution of costs for dobutamine treatment) over 5 years is 268 188 351.94 UAH, when using scenario 2 (100 % distribution for treatment with levosimendan) total budget costs will be in amount of 485 393 073.09 UAH, if scenario 3 is applied (gradual 5 % transition in the treatment of patients with ADCHF with dobutamine for treatment with levosimendan within 5 years), the total budget costs will amount to 289 916 431.92 UAH