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Effect of intensive LDL cholesterol lowering with PCSK9 monoclonal antibodies on tendon xanthoma regression in familial hypercholesterolemia

  • Ana M. Bea
    Affiliations
    Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, CIBERCV, Zaragoza, Spain
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  • Sofia Perez-Calahorra
    Affiliations
    Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, CIBERCV, Zaragoza, Spain
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  • Victoria Marco-Benedi
    Affiliations
    Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, CIBERCV, Zaragoza, Spain
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  • Itziar Lamiquiz-Moneo
    Affiliations
    Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, CIBERCV, Zaragoza, Spain
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  • Estibaliz Jarauta
    Affiliations
    Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, CIBERCV, Zaragoza, Spain
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  • Rocio Mateo-Gallego
    Affiliations
    Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, CIBERCV, Zaragoza, Spain
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  • Fernando Civeira
    Correspondence
    Corresponding author. Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Av. Isabel La Católica, 1-3, 50009 Zaragoza, Spain.
    Affiliations
    Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, CIBERCV, Zaragoza, Spain
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      Highlights

      • This is the first study that assess the intensive LDL cholesterol lowering effect of PCSK9 inhibition on tendon xanthomas.
      • Compared with standard lipid-lowering therapy, the combination with PCSK9 inhibitors showed greater tendon xanthoma regression.
      • Tendon xanthoma regression was observed with mean LDL cholesterol of 60 mg/dL.
      • Some patients developed asymptomatic calcifications inside the Achilles tendon.
      • These results suggest that PCSK9 inhibition is highly efficient regressing lipid deposits in heterozygous familial hypercholesterolemia.

      Abstract

      Background and aims

      The effect of LDLc lowering with PCSK9 antibodies on tendon xanthomas (TX) is unknown.

      Methods

      TX was measured in 24 heterozygous familial hypercholesterolemia (HeFH) cases and in 24 HeFH controls with or without PCSK9 inhibitors for at least one year.

      Results

      Exposure to PCSK9 inhibitors in cases was 2.96 ± 1.33 years. LDLc decreased 80.8 ± 7.66% in cases and 56.9 ± 11.1% in controls. There was a decrease in maximum (−5.03%) and mean (−5.32%) TX in cases but not in controls (+3.97%, +3.16, respectively, p = 0.01). PCSK9 inhibitor treatment was independently associated with TX reduction.

      Conclusion

      Addition of a PCSK9 inhibitor to statin and ezetimibe resulted in a greater decrease in LDLc and TX after 3 years of treatment.

      Keywords

      Abbreviations:

      AT (Achilles Tendon), TX (Tendon Xanthomas), HeFH (Heterozygous Familial hypercholesterolemia), HoFH (Homozygous Familial Hypercholesterolemia), CHD (Coronary Heart Disease), PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9)
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