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Impact of evolocumab treatment on low-density lipoprotein cholesterol levels in heterozygous familial hypercholesterolemic patients withdrawing from regular apheresis

  • Masa-aki Kawashiri
    Correspondence
    Corresponding author. Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan

    Department of Internal Medicine, KKR Hokuriku Hospital, 2-13-43 Izumigaoka, Kanazawa, 921-8035, Japan
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  • Atsushi Nohara
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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  • Toshinori Higashikata
    Affiliations
    Department of Internal Medicine, Komatsu Municipal Hospital, Ho-60 Mukaimoto-ori-cho, Komatsu, 923-8560, Japan
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  • Hayato Tada
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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  • Chiaki Nakanishi
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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  • Hirofumi Okada
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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  • Tetsuo Konno
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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  • Kenji Sakata
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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  • Kenshi Hayashi
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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  • Akihiro Inazu
    Affiliations
    Molecular Biochemistry and Molecular Biology Laboratory, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, 920-0942, Japan
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  • Hiroshi Mabuchi
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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  • Masakazu Yamagishi
    Affiliations
    Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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      Highlights

      • Eleven patients with heterozygous FH under biweekly LDL apheresis were enrolled.
      • All the patients were switched from LDL apheresis to evolocumab injection therapy.
      • Evolocumab significantly reduces LDL-C by 62.5% compared with LDL apheresis.
      • No side effects were documented other than mild reduction in vitamin E serum levels.

      Abstract

      Background and aims

      Low-density lipoprotein (LDL) apheresis has been used to treat refractory hyperlipidemia such as familial hypercholesterolemia (FH). Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor used in clinical settings, can reduce LDL cholesterol (LDL-C) levels by >70%. Therefore, this study aimed to assess the impact of evolocumab on withdrawal from regular LDL apheresis in patients with heterozygous FH (HeFH).

      Methods

      Eleven patients with HeFH undergoing biweekly LDL apheresis were enrolled and were subsequently switched to a biweekly subcutaneous injection of 140 mg of evolocumab. The primary endpoints were percent changes in mean LDL-C and apolipoprotein B (apoB) serum levels, which were averages of two different time point measurements, due to the switch in the treatment method.

      Results

      The mean LDL-C and apoB serum levels significantly reduced from 2.55 ± 0.62 mmol/L to 0.96 ± 0.40 mmol/L (−62.5%, p < 0.0001) and from 82.8 ± 12.3 mg/dL to 45.4 ± 10.9 mg/dL (−45.2%, p < 0.0001), respectively. Serum lipoprotein (a) levels also significantly reduced from 148 (116–351) mg/L to 91 (53–289) mg/L (−38.5%, p < 0.01). The reduction in LDL-C and apoB levels was not associated with the basal serum levels of PCSK9 or cholesterol production/absorption markers. Although evolocumab significantly reduced serum vitamin E levels, they were still within the normal range, and no subjective or objective side effects were observed.

      Conclusions

      Compared to biweekly LDL apheresis, biweekly evolocumab injection therapy is less expensive, less invasive, less time-consuming, and more effective in reducing atherogenic lipoprotein levels without severe adverse side effects.

      Keywords

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