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Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies*

Landoni, Giovanni MD; Biondi-Zoccai, Giuseppe MD; Greco, Massimiliano MD; Greco, Teresa MSc; Bignami, Elena MD; Morelli, Andrea MD; Guarracino, Fabio MD; Zangrillo, Alberto MD

doi: 10.1097/CCM.0b013e318232962a
Review Article

Objective: Catecholaminergic inotropes have a place in the management of low output syndrome and decompensated heart failure but their effect on mortality is debated. Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use. A meta-analysis was conducted to determine the impact of levosimendan on mortality and hospital stay.

Data Sources: BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials were searched for pertinent studies. International experts and the manufacturer were contacted.

Study Selection: Articles were assessed by four trained investigators, with divergences resolved by consensus. Inclusion criteria were random allocation to treatment and comparison of levosimendan vs. control. There were no restrictions on dose or time of levosimendan administration or on language. Exclusion criteria were: duplicate publications, nonadult studies, oral administration of levosimendan, and no data on main outcomes.

Data Extraction: Study end points, main outcomes, study design, population, clinical setting, levosimendan dosage, and treatment duration were extracted.

Data Synthesis: Data from 5,480 patients in 45 randomized clinical trials were analyzed. The overall mortality rate was 17.4% (507 of 2,915) among levosimendan-treated patients and 23.3% (598 of 2,565) in the control group (risk ratio 0.80 [0.72; 0.89], p for effect <.001, number needed to treat = 17 with 45 studies included). Reduction in mortality was confirmed in studies with placebo (risk ratio 0.82 [0.69; 0.97], p = .02) or dobutamine (risk ratio 0.68 [0.52–0.88]; p = .003) as comparator and in studies performed in cardiac surgery (risk ratio 0.52 [0.35; 0.76] p = .001) or cardiology (risk ratio 0.75 [0.63; 0.91], p = .003) settings. Length of hospital stay was reduced in the levosimendan group (weighted mean difference = −1.31 [−1.95; −0.31], p for effect = .007, with 17 studies included). A trend toward a higher percentage of patients experiencing hypotension was noted in levosimendan vs. control (risk ratio 1.39 [0.97–1.94], p = .053).

Conclusions: Levosimendan might reduce mortality in cardiac surgery and cardiology settings of adult patients.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site ( SUPPLEMENTAL DIGITAL CONTENT IS AVAILABLE IN THE TEXT.

From the Department of Anesthesia and Intensive Care (GL, MG, TG, EB, AZ), Università Vita-Salute San Raffaele, Milano, Italy; Interventional Cardiology, Division of Cardiology (GBZ), University of Turin, Turin, Italy; Department of Anesthesiology and Intensive Care (AM), University of Rome, “La Sapienza,” Rome, Italy; Cardiothoracic Department (FG), Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.

* See also p. 702.

The authors have not disclosed any potential conflicts of interest.

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© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins