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

Main Article Content

M. A. Aristov
O. M. Melnychuk

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.

Article Details

Keywords:

levosimendan, inotrope support, acute decompensated chronic heart failure, dobutamine

References

Денисюк В.І. Хронічна серцева недостатність: стандарти діагностики, лікування та профілактики за критеріями доказової медицини // Укр. терапевт. журн.– 2008.– № 2.

Клинические рекомендации ОССН – РКО – РНМОТ. Сердечная недостаточность: хроническая (ХСН) и острая декомпенсированная (ОДСН) Диагностика, профилактика и лечение // Кардиология.– 2018.– № 58 (S6). doi: https://doi.org/10.18087/cardio.2475.

Стецюк О.М., Лелека М.В., Арістов М.А. Інотропна підтримка пацієнтів з гострим інфарктом міокарда та серцевою недостатністю важкого ступеня – застосування левосимендану порівняно з добутаміном. Результати НТА в Україні // Журнал HTA.– 2019. https://hta.ua/dijalnist/zhurnal-hta/zhurnal.html.

Adamopoulos S., Parissis J.T., Iliodromitiset E.K. et al. Effects of Levosimendan Versus Dobutamine on Inflammatory and Apoptotic Pathways in Acutely Decompensated Chronic Heart Failure // Am. J. Cardiol.– 2006.– Vol. 98.– P. 102–106. doi: https://doi.org/10.1016/j.amjcard.2006.01.068.

Bocchi Е.А. et al. Guidelines for the Assessment and Management of Decompensated Heart Failure // Arq. Bras. Cardiol.– 2005.– Vol. 85 (Suppl. 3).– P. 49–94.– 1–48.

Cleland J.G.F., Takala A., Apajasalo M. et al. Intravenous levosimendan treatment is cost-effective compared with dobutamine in severe low-output heart failure: an analysis based on the international LIDO trial // Eur. J. Heart Fail.– 2003.– P. 101–108. doi: https://doi.org/10.1016/S1388-9842(02)00246-5.

Crespo-Leiro M.G., Anker S.D., Maggioni A.P. et al. on behalf of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions // Eur. J. Heart Fail.– 2016.– Vol. 18.– P. 613–625. doi: https://doi.org/10.1002/ejhf.566.

De Luca L., Fonarow G.C., Adams J. K.F. et al. Acute Heart failure syndromes: clinical scenarios and pathophysiologic targets for therapy // Heart Fail. Rev.– 2007.– Vol. 12 (2).– P. 97–104. doi: https://doi.org/10.1007/s10741-007-9011-8.

Duygu H., Turk U., Ozdoganet O. et al. Levosimendan versus Dobutamine in Heart Failure Patients

Treated Chronically with Carvedilol // Cardiovasc. Therapeutics.– 2008.– Vol. 26.– P. 182–188. doi: https://doi.org/10.1111/j.1755-5922.2008.00050.x.

Follath F., Cleland J.G.F., Just H. et al., for the Steering Committee and Investigators of the Levosimendan Infusion versus Dobutamine (LIDO) Study. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial // Lancet.– 2002.– Vol. 360 (9328).– P. 196–202. doi: https://doi.org/10.1016/s0140-6736(02)09455-2.

Gheorghiade M., Filippatos G., De Luca L., Burnett J. Congestion in acute heart failure syndromes: an essential target of evaluation and treatment // Am. J. Med.– 2006.– Vol. 119 (12A). doi: https://doi.org/10.1016/j.amjmed.2006.09.011. https://moz.gov.ua/reestr-optovo-vidpusknih-cin-na-likarski-zasobi

Larg A., Moss J.R. Cost-of-Illness Studies. A Guide to Critical Evaluation // Pharmacoeconomics.– 2011.– Vol. 29 (8).– P. 653–671. doi: https://doi.org/10.2165/11588380-000000000-00000.

Lepage S. Acute decompensated heart failure // Can. J. Cardiol.– 2008.– Vol. 24 (Suppl. B).– P. 6B–8B. doi: https://doi.org/10.1016/s0828-282x(08)71022-5.

Maggioni A.P., Dahlström U., Filippatos G. et al. on behalf of the Heart Failure Association of the European Society of Cardiology (HFA). EURObservational Research Prog­­ ramme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot) // Eur. J. Heart Fail.– 2013.– Vol. 15.– P. 808–817. doi: https://doi.org/10.1093/eurjhf/hft050.

Marseille E., Larson B., Kazi D.S. et al. Thresholds for the cost–effectiveness of interventions: alternative approaches // Bull. World Health Organization.– 2015.– Vol. 93.– P. 118–124. doi: https://doi.org/10.2471/BLT.14.138206.

McMurray J.J.V., Adamopoulos S., Anker S.D. et al. for the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA). ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure. 2012 // Eur. Heart J.– 2012.– Vol. 33.– P. 1787–1847. doi: https://doi.org/10.1093/eurheartj/ehs104.

Mebazaa A., Nieminen M.S., Filippatos G.S. et al. Levosimendan vs. dobutamine: outcomes for acute heart failure patients on b-blockers in SURVIVE // Eur. J. Heart Failure.– 2009.– Vol. 11.– P. 304–311. doi: https://doi.org/10.1093/eurjhf/hfn045.

Mosterd A., Hoes A.W. Clinical epidemiology of heart failure // Heart.– 2007.– Vol. 93 (9).– P. 1137–1146. doi: https://doi.org/10.1136/hrt.2003.025270.

Nieminen M.S., Brutsaert D., Dickstein K. et al. on behalf of the EuroHeart Survey Investigators. EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population // Eur. Heart J.– 2006.– Vol. 27.– P. 2725–2736. doi: https://doi.org/10.1093/eurheartj/ehl193.

Rawlins M.D. NICE and the public health // Brit. J. Clin. Pharmacology.– 2004.– Vol. 58.– P. 575–580. doi: https://doi.org/10.1111/j.1365-2125.2004.02195.x.

Severino P., Mather P.J., Pucci M. et al. Advanced Heart Failure and End-Stage Heart Failure: Does a Difference Exist // Diagnostics.– 2019.– Vol. 9 (4).– P. 170. doi: https://doi.org/10.3390/diagnostics9040170.

Störk S., Handrock R., Jacob J. et al. Epidemiology of heart failure in Germany: a retrospective database study // Clin. Res. Cardiol.– 2017.– Vol. 106 (11).– P. 913–922. doi: https://doi.org/10.1007/s00392-017-1137-7.

Swedberg K., Kjekshus J., Snapinn S. Long term survival in severe heart failure patients treated with enalapril. Ten year follow-up of CONSENSUS I // Eur. Heart J.– 1999.– Vol. 20.– P. 136–139. doi: https://doi.org/10.1053/euhj.1998.1098.

Tsuyuki R.T., Shibata M.C., Nilsson C. et al. Contemporary burden of illness of congestive heart failure in Canada // Can. J. Cardiol.– 2003.– Vol. 19 (4).– P. 436–438.

Weinstein M.C., Stason W.B. Foundations of cost-effectiveness analysis for health and medical practice // NEJM.– 1977.– Vol. 296.– P. 716–721. doi: https://doi.org/10.1056/NEJM197703312961304. www.health-ua.com

Yancy C.W., Jessup M., Bozkurt B. et al. 2013 ACCF/AHA CHF Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines // Circulation.– 2013.– Vol. 128.– P. e240–e327. doi: https://doi.org/10.1161/CIR.0b013e31829e8776.

Yilmaz M.B., Yontar C., Karadas A.E.F. et al. Comparative effects of levosimendan and dobutamine on right ventricular function in patients with biventricular heart failure // Heart Vessels.– 2009.– Vol. 24.– Р. 16–21.

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