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Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment.
Stiekema, Lotte C A; Stroes, Erik S G; Verweij, Simone L; Kassahun, Helina; Chen, Lisa; Wasserman, Scott M; Sabatine, Marc S; Mani, Venkatesh; Fayad, Zahi A.
  • Stiekema LCA; Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, AZ Amsterdam, The Netherlands.
  • Stroes ESG; Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, AZ Amsterdam, The Netherlands.
  • Verweij SL; Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, AZ Amsterdam, The Netherlands.
  • Kassahun H; Department of Clinical Development, Amgen Inc., One Amgen Center Drive Thousand Oaks, CA, USA.
  • Chen L; Department of Biostatistics, Amgen Inc., One Amgen Center Drive Thousand Oaks, CA, USA.
  • Wasserman SM; Department of Clinical Development, Amgen Inc., One Amgen Center Drive Thousand Oaks, CA, USA.
  • Sabatine MS; Division of Cardiovascular Medicine, TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Fenwood Road, Boston, MA, USA.
  • Mani V; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl, New York, NY, USA.
  • Fayad ZA; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl, New York, NY, USA.
Eur Heart J ; 40(33): 2775-2781, 2019 09 01.
Article en En | MEDLINE | ID: mdl-30561610
ABSTRACT

AIMS:

Subjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a). METHODS AND

RESULTS:

In this multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median [interquartile range (IQR)] age 60.0 [54.0-67.0] years, Lp(a) 200.0 [155.5-301.5] nmol/L [80.0 (62.5-121.0) mg/dL]; mean [standard deviation (SD)] LDL-C 3.7 [1.0] mmol/L [144.0 (39.7) mg/dL]; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420 mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% [95% confidence interval (CI) 65.8-55.5] and Lp(a) by 13.9% (95% CI 19.3-8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L [60.1 (28.1) mg/dL], and the median (IQR) Lp(a) level was 188.0 (140.0-268.0) nmol/L [75.2 (56.0-107.2) mg/dL]. Arterial wall inflammation [most diseased segment target-to-background ratio (MDS TBR)] in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (-8.3%) vs. placebo (-5.3%) [treatment difference -3.0% (95% CI -7.4% to 1.4%); P = 0.18].

CONCLUSION:

Evolocumab treatment in patients with median baseline Lp(a) 200.0 nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Arteritis / Lipoproteína(a) / Anticuerpos Monoclonales Humanizados / Proproteína Convertasa 9 / LDL-Colesterol / Anticolesterolemiantes Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2019 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Arteritis / Lipoproteína(a) / Anticuerpos Monoclonales Humanizados / Proproteína Convertasa 9 / LDL-Colesterol / Anticolesterolemiantes Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2019 Tipo del documento: Article