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Levosimendan Can Improve the Level of B-Type Natriuretic Peptide and the Left Ventricular Ejection Fraction of Patients with Advanced Heart Failure: A Meta-analysis of Randomized Controlled Trials

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Abstract

Background and Aims

Levosimendan, a calcium (Ca2+)-sensitizing cardiotonic agent, is mainly used in patients with advanced heart failure. However, no research could explain how levosimendan reduces the mortality in advanced heart failure patients. We aim to illustrate the efficacy of levosimendan through clinical indexes.

Methods

We searched PubMed, Embase, and CENTRAL from 1994 to August 2019 to compare the efficacy of levosimendan infusion for the treatment of advanced heart failure with that of other agents (placebo, dobutamine, furosemide, and prostaglandin E1). Levels of B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP), and left ventricular ejection fraction (LVEF) and heart rate (HR) were analyzed. The count data were analyzed by the standardized mean difference (SMD) and its 95% confidence interval (CI) to determine the effect size. We chose the random effect model or the fixed effect model according to the heterogeneity.

Results

Nine randomized controlled trials with 413 patients were ultimately enrolled. Compared with other agents (placebo, dobutamine, furosemide, and prostaglandin E1), levosimendan significantly reduced the BNP level (SMD − 0.91; 95% CI − 1.44 to − 0.39; p = 0.001; I2 = 74.3%) and improved the LVEF (SMD 0.74; 95% CI 0.22–1.25; p = 0.005; I2 = 79.7%). However, levosimendan did not significantly change the HR (SMD 0.09; 95% CI − 0.24 to 0.42; p = 0.592; I2 = 51.5%). Meanwhile, we found that the main source of heterogeneity was the use of loaded or unloaded levosimendan.

Conclusion

Our meta-analysis suggests that intravenous levosimendan can reduce BNP level and increase LVEF in patients with advanced heart failure to reduce the mortality at the shortest follow-up available.

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Funding

No external funding was used in the preparation of this article.

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Authors and Affiliations

  1. Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Diyu Cui, Yimeng Liao, Gege Li & Yunqing Chen

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  1. Diyu Cui
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  2. Yimeng Liao
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  3. Gege Li
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Contributions

Conceptualization: DYC and YML; search and search screening: DYC, YML, GGL, and YQC; data extraction, data validation, and quality assessment: DYC, YML, and YQC; statistical analysis and interpretation of results: DYC, YML, and YQC; writing original draft preparation: DYC; writing review and editing: DYC. All authors have read and approved the final version.

Corresponding author

Correspondence to Yunqing Chen.

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Conflict of interest

Diyu Cui, Yimeng Liao, Gege Li, and Yunqing Chen declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

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Cui, D., Liao, Y., Li, G. et al. Levosimendan Can Improve the Level of B-Type Natriuretic Peptide and the Left Ventricular Ejection Fraction of Patients with Advanced Heart Failure: A Meta-analysis of Randomized Controlled Trials. Am J Cardiovasc Drugs 21, 73–81 (2021). https://doi.org/10.1007/s40256-020-00416-y

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