Full Text:   <2139>

CLC number: R541.6

On-line Access: 2013-05-04

Received: 2012-10-23

Revision Accepted: 2013-04-01

Crosschecked: 2013-04-12

Cited: 13

Clicked: 3546

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2013 Vol.14 No.5 P.400-415

10.1631/jzus.B1200290


Levosimendan versus dobutamine in critically ill patients: a meta-analysis of randomized controlled trials


Author(s):  Xuan Huang, Shu Lei, Mei-fei Zhu, Rong-lin Jiang, Li-quan Huang, Guo-lian Xia, Yi-hui Zhi

Affiliation(s):  Department of Gastroenterology, the First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310006, China; more

Corresponding email(s):   fishmanshu@163.com

Key Words:  Heart failure, Levosimendan, Mortality, Survival, Dobutamine


Xuan Huang, Shu Lei, Mei-fei Zhu, Rong-lin Jiang, Li-quan Huang, Guo-lian Xia, Yi-hui Zhi. Levosimendan versus dobutamine in critically ill patients: a meta-analysis of randomized controlled trials[J]. Journal of Zhejiang University Science B, 2013, 14(5): 400-415.

@article{title="Levosimendan versus dobutamine in critically ill patients: a meta-analysis of randomized controlled trials",
author="Xuan Huang, Shu Lei, Mei-fei Zhu, Rong-lin Jiang, Li-quan Huang, Guo-lian Xia, Yi-hui Zhi",
journal="Journal of Zhejiang University Science B",
volume="14",
number="5",
pages="400-415",
year="2013",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1200290"
}

%0 Journal Article
%T Levosimendan versus dobutamine in critically ill patients: a meta-analysis of randomized controlled trials
%A Xuan Huang
%A Shu Lei
%A Mei-fei Zhu
%A Rong-lin Jiang
%A Li-quan Huang
%A Guo-lian Xia
%A Yi-hui Zhi
%J Journal of Zhejiang University SCIENCE B
%V 14
%N 5
%P 400-415
%@ 1673-1581
%D 2013
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1200290

TY - JOUR
T1 - Levosimendan versus dobutamine in critically ill patients: a meta-analysis of randomized controlled trials
A1 - Xuan Huang
A1 - Shu Lei
A1 - Mei-fei Zhu
A1 - Rong-lin Jiang
A1 - Li-quan Huang
A1 - Guo-lian Xia
A1 - Yi-hui Zhi
J0 - Journal of Zhejiang University Science B
VL - 14
IS - 5
SP - 400
EP - 415
%@ 1673-1581
Y1 - 2013
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1200290


Abstract: 
Objective: To evaluate the clinical efficacy of levosimendan versus dobutamine in critically ill patients requiring inotropic support. Methods: Clinical trials were searched in PubMed, EMBASE, and the Cochrane Central Registry of Clinical Trials, as well as Web of Science. Studies were included if they compared levosimendan with dobutamine in critically ill patients requiring inotropic support, and provided at least one outcome of interest. Outcomes of interest included mortality, incidence of hypotension, supraventricular arrhythmias, and ventricular arrhythmias. Results: Data from a total of 3052 patients from 22 randomized controlled trials (RCTs) were included in the analysis. Overall analysis showed that the use of levosimendan was associated with a significant reduction in mortality (269 of 1373 [19.6%] in the levosimendan group, versus 328 of 1278 [25.7%] in the dobutamine group, risk ratio (RR)=0.81, 95% confidence interval (CI) 0.70–0.92, P for effect=0.002). Subgroup analysis indicated that the benefit from levosimendan could be found in the subpopulations of cardiac surgery, ischemic heart failure, and concomitant β-blocker therapy in comparison with dobutamine. There was no significant difference in the incidence of hypotension, supraventricular arrhythmias, or ventricular arrhythmias between the two drugs. Conclusions: In contrast with dobutamine, levosimendan is associated with a significant improvement in mortality in critically ill patients requiring inotropic support. Patients having cardiac surgery, with ischemic heart failure, and receiving concomitant β-blocker therapy may benefit from levosimendan. More RCTs are required to address the questions about no positive outcomes in the subpopulation in a cardiology setting, and to confirm the advantages in long-term prognosis.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Abraham, W.T., Adams, K.F., Fonarow, G.C., Costanzo, M.R., Berkowitz, R.L., LeJemtel, T.H., Cheng, M.L., Wynne, J., 2005. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J. Am. Coll. Cardiol., 46(1):57-64.

[2]Adamopoulos, S., Parissis, J.T., Iliodromitis, E.K., Paraskevaidis, I., Tsiapras, D., Farmakis, D., Karatzas, D., Gheorghiade, M., Filippatos, G.S., Kremastinos, D.T., 2006. Effects of levosimendan versus dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure. Am. J. Cardiol., 98(1):102-106.

[3]Alhashemi, J.A., Alotaibi, Q.A., Abdullah, G.M., Shalabi, S.A., 2009. Levosimendan vs dobutamine in septic shock. J. Crit. Care, 24(3):e14.

[4]Alvarez, J., Taboada, M., Rodríguez, J., Caruezo, V., Bouzada, M., Campaña, O., Bascuas, B., Pérez-Paz, J., Ginesta, V., 2005. Hemodynamic effects of levosimendan following cardiac surgery. Rev. Esp. Anestesiol. Reanim., 52(7):389-394.

[5]Alvarez, J., Bouzada, M., Fernández, A.L., Caruezo, V., Taboada, M., Rodríguez, J., Ginesta, V., Rubio, J., García-Bengoechea, J.B., González-Juanatey, J.R., 2006. Hemodynamic effects of levosimendan compared with dobutamine in patients with low cardiac output after cardiac surgery. Rev. Esp. Cardiol., 59(4):338-345 (in Spanish).

[6]Bayram, M., de Luca, L., Massie, M.B., Gheorghiade, M., 2005. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am. J. Cardiol., 96(6A):47G-58G.

[7]Bergh, C.H., Andersson, B., Dahlstrom, U., Forfang, K., Kivikko, M., Sarapohja, T., Ullman, B., Wikstrom, G., 2010. Intravenous levosimendan vs. dobutamine in acute decompensated heart failure patients on β-blockers. Eur. J. Heart Fail., 12(4):404-410.

[8]Bonios, M.J., Terrovitis, J.V., Drakos, S.G., Katsaros, F., Pantsios, C., Nanas, S.N., Kanakakis, J., Alexopoulos, G., Toumanidis, S., Anastasiou-Nana, M., et al., 2012. Comparison of three different regimens of intermittent inotrope infusions for end stage heart failure. Int. J. Cardiol., 159(3):225-229.

[9]Cleland, J.G.F., Freemantle, N., Coletta, A.P., Clark, A.L., 2006. Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE. Eur. J. Heart Fail., 8(1):105-110.

[10]Costanzo, M.R., Johannes, R.S., Pine, M., Gupta, V., Saltzberg, M., Hay, J., Yancy, C.W., Fonarow, G.C., 2007. The safety of intravenous diuretics alone versus diuretics plus parenteral vasoactive therapies in hospitalized patients with acutely decompensated heart failure: a propensity score and instrumental variable analysis using the Acutely Decompensated Heart Failure National Registry (ADHERE) database. Am. Heart J., 154(2):267-277.

[11]de Backer, D., Biston, P., Devriendt, J., Madl, C., Chochrad, D., Aldecoa, C., Brasseur, A., Defrance, P., Gottignies, P., Vincent, J.L., 2010. Comparison of dopamine and norepinephrine in the treatment of shock. N. Engl. J. Med., 362(9):779-789.

[12]Delaney, A., Bradford, C., McCaffrey, J., Bagshaw, S.M., Lee, R., 2010. Levosimendan for the treatment of acute severe heart failure: a meta-analysis of randomized controlled trials. Int. J. Cardiol., 138(3):281-289.

[13]Dellinger, R.P., Levy, M.M., Carlet, J.M., Bion, J., Parker, M.M., Jaeschke, R., Reinhart, K., Angus, D.C., Brun-Buisson, C., Beale, R., et al., 2008. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Crit. Care Med., 36(1):296-327.

[14]Dickstein, K., Cohen-Solal, A., Filippatos, G., McMurray, J.J., Ponikowski, P., Poole-Wilson, P.A., Strömberg, A., van Veldhuisen, D.J., Atar, D., Hoes, A.W., et al., 2008. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur. Heart J., 29(19):2388-2442.

[15]Duygu, H., Ozerkan, F., Nalbantgil, S., Zoghi, M., Akilli, A., Akin, M., Nazli, C., Ergene, O., 2008a. Effect of levosimendan on E/E′ ratio in patients with ischemic heart failure. Int. J. Cardiol., 123(2):201-203.

[16]Duygu, H., Turk, U., Ozdogan, O., Akyuz, S., Kirilmaz, B., Alioglu, E., Gunduz, R., Bozkaya, Y.T., Turkoglu, C., Payzin, S., 2008b. Levosimendan versus dobutamine in heart failure patients treated chronically with carvedilol. Cardiovasc. Ther., 26(3):182-188.

[17]Follath, F., 2009. Newer treatments for decompensated heart failure: focus on levosimendan. Drug Des. Devel. Ther., 3:73-78.

[18]Follath, F., Hinkka, S., Jager, D., Just, H., Mitrovic, V., Papp, J.G., Peuhkurinen, K., Sandell, E., Takkunen, O., Lehtonen, L., 1999. Dose-ranging and safety with intravenous levosimendan in low-output heart failure: experience in three pilot studies and outline of the levosimendan infusion versus dobutamine (LIDO) trial. Am. J. Cardiol., 83(12B):21I-25I.

[19]Follath, F., Cleland, J.G., Just, H., Papp, J.G., Scholz, H., Peuhkurinen, K., Harjola, V.P., Mitrovic, V., Abdalla, M., Sandell, E.P., et al., 2002. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low output heart failure (the LIDO study): a randomized double-blind trial. Lancet, 360(9328):196-202.

[20]Haikala, H., Nissinen, E., Etemadzadeh, E., Levijoki, J., Lindén, I.B., 1995. Troponin C-mediated calcium sensitization induced by levosimendan does not impair relaxation. J. Cardiovasc. Pharmacol., 25(5):794-801.

[21]Haynes, R.B., McKibbon, K.A., Wilczynski, N.L., Walter, S.D., Were, S.R., 2005. Optimal search strategies for retrieving scientifically strong studies of treatment from Medline: analytical survey. BMJ, 330(7501):1179.

[22]Higgins, J.P., Thompson, S.G., Deeks, J.J., Altman, D.G., 2003. Measuring inconsistency in meta-analyses. BMJ, 327(7414):557-560.

[23]Hunt, S.A., Abraham, W.T., Chin, M.H., Feldman, A.M., Francis, G.S., Ganiats, T.G., Jessup, M., Konstam, M.A., Mancini, D.M., Michl, K., et al., 2005. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult. Circulation, 112(12):e154-e235.

[24]Iyisoy, A., Celik, T., Celik, M., Bugan, B., Yaman, H., 2010. Comparative effects of levosimendan and dobutamine infusion on p wave dispersion in patients with acute decompensated heart failure. Turkish J. Med. Sci., 40(5):761-770.

[25]Kaheinen, P., Pollesello, P., Levijoki, J., Haikala, H., 2001. Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels. J. Cardiovasc. Pharmacol., 37(4):367-374.

[26]Landoni, G., Mizzi, A., Biondi-Zoccai, G., Bignami, E., Prati, P., Ajello, V., Marino, G., Guarracino, F., Zangrillo, A., 2010a. Levosimendan reduces mortality in critically ill patients. A meta-analysis of randomized controlled studies. Minerva Anestesiol., 76(4):276-286.

[27]Landoni, G., Mizzi, A., Biondi-Zoccai, G., Bruno, G., Bignami, E., Corno, L., Zambon, M., Gerli, C., Zangrillo, A., 2010b. Reducing mortality in cardiac surgery with levosimendan: a meta-analysis of randomized controlled trials. J. Cardiothorac. Vasc. Anesth., 24(1):51-57.

[28]Landoni, G., Biondi-Zoccai, G., Greco, M., Greco, T., Bignami, E., Morelli, A., Guarracino, F., Zangrillo, A., 2012. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit. Care Med., 40(2):634-646.

[29]Lehtonen, L., Sundberg, S., 2002. The contractility enhancing effect of the calcium sensitizer levosimendan is not attenuated by carvedilol in healthy subjects. Eur. J. Clin. Pharmacol., 58(7):449-452.

[30]Levin, R., Degrange, M.A., Del-Mazo, C., Porcile, R., Tanus, E., Blanco, N., Salvagio, F., Botbol, L., Milman, V., 2008a. Superiority of levosimendan over dobutamine in low cardiac output syndrome after aortic valve replacement. Circulation, 118:E231.

[31]Levin, R., Degrange, M.A., Porcile, R., Salvagio, F., Blanco, N., Botbol, A.L., Tanus, E., Del Mazo, C.D., 2008b. The calcium sensitizer levosimendan gives superior results to dobutamine in postoperative low cardiac output syndrome. Rev. Esp. Cardiol., 61(5):471-479.

[32]Levin, R., Porcile, R., Salvagio, F., Mazo, C.D., Botbol, A., Tanus, E., Blanco, N., Degrange, M., 2009. Levosimendan reduces mortality in postoperative low cardiac output syndrome after coronary surgery. Circulation, 120:S987.

[33]Maharaj, R., Metaxa, V., 2011. Levosimendan and mortality after coronary revascularisation: a meta-analysis of randomized controlled trials. Crit. Care, 15(3):R140.

[34]McMurray, J.J., Adamopoulos, S., Anker, S.D., Auricchio, A., Böhm, M., Dickstein, K., Falk, V., Filippatos, G., Fonseca, C., Gomez-Sanchez, M.A., et al., 2012. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: 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) of the ESC. Eur. J. Heart Fail., 14(8):803-869.

[35]Mebazaa, A., Nieminen, M.S., Packer, M., Cohen-Solal, A., Kleber, F.X., Pocock, S.J., Thakkar, R., Padley, R.J., Poder, P., Kivikko, M., 2007. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE randomized trial. JAMA, 297(17):1883-1891.

[36]Mebazaa, A., Pitsis, A.A., Rudiger, A., Toller, W., Longrois, D., Ricksten, S.E., Bobek, I., de Hert, S., Wieselthaler, G., Schirmer, U., et al., 2010. Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery. Crit. Care, 14(2):201.

[37]Mebazaa, A., Parissis, J., Porcher, R., Gayat, E., Nikolaou, M., Boas, F.V., Delgado, J.F., Follath, F., 2011. Short-term survival by treatment among patients hospitalized with acute heart failure: the global ALARM-HF registry using propensity scoring methods. Intensive Care Med., 37(2):290-301.

[38]Metra, M., Nodari, S., D′Aloia, A., Muneretto, C., Robertson, A.D., Bristow, M.R., Dei Cas, L., 2002. β-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol. J. Am. Coll. Cardiol., 40(7):1248-1258.

[39]Morelli, A., de Castro, S., Teboul, J.L., Singer, M., Rocco, M., Conti, G., de Luca, L., di Angelantonio, E., Orecchioni, A., Pandian, N.G., et al., 2005. Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression. Intensive Care Med., 31(5):638-644.

[40]Nieminen, M.S., Akkila, J., Hasenfuss, G., Kleber, F.X., Lehtonen, L.A., Mitrovic, V., Nyquist, O., Remme, W.J., 2000. Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J. Am. Coll. Cardiol., 36(6):1903-1912.

[41]Pacold, I., Kleinman, B., Gunnar, R., Loeb, H.S., 1983. Effects of low-dose dobutamine on coronary hemodynamics, myocardial metabolism and anginal threshold in patients with coronary artery disease. Circulation, 68(5):1044-1050.

[42]Parissis, J.T., Rafouli-Stergiou, P., Stasinos, V., Psarogiannakopoulos, P., Mebazaa, A., 2010. Inotropes in cardiac patients: update 2011. Curr. Opin. Crit. Care, 16(5):432-441.

[43]Ribeiro, R.A., Rohde, L.E., Polanczyk, C.A., 2010. Levosimendan in acute decompensated heart failure: systematic review and meta-analysis. Arq. Bras. Cardiol., 95(2):230-237.

[44]Samimi-Fard, S., Garcia-Gonzalez, M.J., Dominguez-Rodriguez, A., Abreu-González, P., 2008. Effects of levosimendan versus dobutamine on long-term survival of patients with cardiogenic shock after primary coronary angioplasty. Int. J. Cardiol., 127(2):284-287.

[45]Singer, M., 2007. Catecholamine treatment for shock-equally good or bad? Lancet, 370(9588):636-637.

[46]Swedberg, K., Cleland, J., Dargie, H., Drexler, H., Follath, F., Komajda, M., Tavazzi, L., Smiseth, O.A., Gavazzi, A., Haverich, A., et al., 2005. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): the Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur. Heart J., 26(11):1115-1140.

[47]Tavares, M., Rezlan, E., Vostroknoutova, I., Khouadja, H., Mebazaa, A., 2008. New pharmacologic therapies for acute heart failure. Crit. Care. Med., 36(1):S112-S120.

[48]Thackray, S., Easthaugh, J., Freemantle, N., Cleland, J.G., 2002. The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure—a meta-regression analysis. Eur. J. Heart Fail., 4(4):515-529.

[49]Vaitsis, J., Michalopoulou, H., Thomopoulos, C., Massias, S., Stamatis, P., 2009. Use of levosimendan in myocardial dysfunction due to sepsis. Crit. Care, 13(S1):165.

[50]Wang, L., Cui, L., Wei, J.P., Li, G.P., Qi, G.X., Hao, Y.M., Wang, W.Z., Li, H.M., Liu, J., Jiang, D.J., et al., 2010. Efficacy and safety of intravenous levosimendan compared with dobutamine in decompensated heart failure. Chin. J. Cardiovasc. Dis., 38(6):527-530 (in Chinese).

[51]Wong, S.S., Wilczynski, N.L., Haynes, R.B., 2006. Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE. J. Med. Libr. Assoc., 94(1):41-47.

[52]Yilmaz, M.B., Yontar, C., Erdem, A., Karadas, F., Yalta, K., Turgut, O.O., Yilmaz, A., Tandogan, I., 2009. Comparative effects of levosimendan and dobutamine on right ventricular function in patients with biventricular heart failure. Heart Vessels, 24(1):16-21.

[53]Yontar, O.C., Yilmaz, M.B., Yalta, K., Erdem, A., Tandoganet, I., 2010. Acute effects of levosimendan and dobutamine on QRS duration in patients with heart failure. Arq. Bras. Cardiol., 95(6):738-742.

[54]Zairis, M.N., Apostolatos, C., Anastasiadis, P., Mytas, D., Katsaris, C., Kouris, N., Grassos, H., Karidis, K., Adamopoulou, E., Argyrakis, S., et al., 2004. The effect of a calcium sensitizer or an inotrope or none in chronic low output decompensated heart failure: results from the calcium sensitizer or inotrope or none in low output heart failure study (CASINO). J. Am. Coll. Cardiol., 43(5):A206.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE