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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

  • Kamal Awad
  • Dimitri P. Mikhailidis
  • Niki Katsiki
  • Paul Muntner
  • Maciej Banach
  • on behalf of Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group
Systematic Review

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.

Notes

Author 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.

Compliance with Ethical Standards

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.

Supplementary material

40265_2018_870_MOESM1_ESM.docx (20 kb)
Supplementary material 1 (DOCX 19 kb)
40265_2018_870_MOESM2_ESM.docx (17 kb)
Supplementary material 2 (DOCX 16 kb)
40265_2018_870_MOESM3_ESM.tif (1.7 mb)
Supplementary figure 1 Risk of bias summary according to Cochrane Risk of Bias assessment tool
40265_2018_870_MOESM4_ESM.tif (327 kb)
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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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Kamal Awad
    • 1
  • Dimitri P. Mikhailidis
    • 2
  • Niki Katsiki
    • 3
  • Paul Muntner
    • 4
  • Maciej Banach
    • 5
    • 6
    • 7
  • on behalf of Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group
  1. 1.Faculty of MedicineZagazig UniversityZagazigEgypt
  2. 2.Department of Clinical BiochemistryUniversity College London Medical School, University College London (UCL)LondonUK
  3. 3.Second Propedeutic Department of Internal Medicine, Medical SchoolAristotle University of Thessaloniki, Hippokration HospitalThessalonikiGreece
  4. 4.Department of EpidemiologyUniversity of Alabama at BirminghamBirminghamUSA
  5. 5.Head Department of HypertensionWAM University Hospital in Lodz, Medical University of Lodz (MUL)LodzPoland
  6. 6.Polish Mother’s Memorial Hospital Research Institute (PMMHRI)LodzPoland
  7. 7.Cardiovascular Research CentreUniversity of Zielona GoraZielona GoraPoland

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