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Effect of Ezetimibe Monotherapy on Plasma Lipoprotein(a) Concentrations in Patients with Primary Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Abstract

Background and Aims

Ezetimibe reduces plasma low-density lipoprotein cholesterol (LDL-C) levels by up to 20%. However, its effect on plasma lipoprotein(a) [Lp(a)] concentrations in patients with primary hypercholesterolemia has not been defined.

Objective

Therefore, we performed a systematic review and meta-analysis to assess this effect based on the available randomized controlled trials (RCTs).

Methods

We searched the PubMed and SCOPUS databases from inception until 28 February 2017 to identify RCTs that investigated the effect of ezetimibe monotherapy on plasma Lp(a) concentrations in patients with primary hypercholesterolemia. We pooled mean percentage changes in plasma Lp(a) concentrations as a mean difference (MD) with a 95% confidence interval (CI).

Results

Seven RCTs with 2337 patients met the selection criteria and were included in the analysis. Overall pooled analysis suggested that ezetimibe 10 mg significantly reduced plasma Lp(a) concentrations in patients with primary hypercholesterolemia by − 7.06% (95% CI − 11.95 to − 2.18; p = 0.005) compared with placebo. No significant heterogeneity was observed (χ2 = 5.34; p = 0.5). Excluding one study from the analysis resulted in insignificant differences between the two groups (p = 0.2). Meta-regression did not find a significant association between the mean percentage changes in Lp(a) and other potential moderator variables, which included the mean percentage changes of LDL-C concentrations (p = 0.06) and baseline Lp(a) mean values (p = 0.46).

Conclusions

Ezetimibe monotherapy (10 mg/day) showed a small (7.06%) but statistically significant reduction in the plasma levels of Lp(a) in patients with primary hypercholesterolemia. According to current literature, this magnitude of reduction seems to have no clinical relevance. However, further studies are warranted to clarify the mechanism mediating this effect of ezetimibe and to investigate its efficacy in combination with other drugs that have shown promise in lowering Lp(a) levels.

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No external funding was used in the conduct of this work.

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Authors and Affiliations

  1. Faculty of Medicine, Zagazig University, Zagazig, 44519, El-Sharkia, Egypt

    Kamal Awad

  2. Department of Clinical Biochemistry, University College London Medical School, University College London (UCL), Royal Free Campus, London, UK

    Dimitri P. Mikhailidis

  3. Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

    Niki Katsiki

  4. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Paul Muntner

  5. Head Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz (MUL), Lodz, Poland

    Maciej Banach

  6. Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland

    Maciej Banach

  7. Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland

    Maciej Banach

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  1. Kamal Awad
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on behalf of Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group

Contributions

KA contributed to the literature search, screening, data extraction, data analysis, and manuscript writing; DPM to the manuscript writing and revision; NK to the screening, data extraction, and manuscript writing; PM to the manuscript writing and revision; and MB to the study design, supervision, coordination and manuscript writing, and revision. All authors approved the final article.

Corresponding author

Correspondence to Kamal Awad.

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Conflict of interest

DPM has given talks and attended conferences sponsored by MSD, AstraZeneca, and Libytec. NK has given talks, attended conferences, and participated in trials sponsored by Amgen, Angelini, Astra Zeneca, Boehringer Ingelheim, MSD, Novartis, NovoNordisk, Sanofi, and WinMedica. PM has received grant support and honoraria from Amgen. MB has received advisory board fees from Abbott Vascular, Amgen, Daichi Sankyo, Esperion, Lilly, MSD, Resverlogix, and Sanofi-Aventis; speakers bureau fees from Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Sanofi-Aventis, and Valeant; and grants from Valeant and Sanofi-Aventis. KA has no conflicts of interest that are directly relevant to the content of this review.

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Supplementary figure 1 Risk of bias summary according to Cochrane Risk of Bias assessment tool

40265_2018_870_MOESM4_ESM.tif

Supplementary figure 2 The Doi plot displaying publication bias in the studies reporting the impact of ezetimibe monotherapy on plasma Lp(a) concentrations in patients with primary hypercholesterolemia. WMD weighted mean difference

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Awad, K., Mikhailidis, D.P., Katsiki, N. et al. Effect of Ezetimibe Monotherapy on Plasma Lipoprotein(a) Concentrations in Patients with Primary Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Drugs 78, 453–462 (2018). https://doi.org/10.1007/s40265-018-0870-1

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