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Serial magnetic resonance imaging detects a rapid reduction in plaque lipid content under PCSK9 inhibition with alirocumab

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Abstract

PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events. The clinical benefits presumably result from favorable effects on atherosclerotic plaques. Lipid-core and plaque inflammation have been recognized as main determinants of risk for plaque rupture and cardiovascular events. Both can be noninvasively assessed with carotid MRI. We studied if PCSK9 inhibition with alirocumab induces regression in lipid-core or plaque inflammation within 6 months as measured by MRI. Patients with non-calcified carotid plaque(s) and baseline LDL-C ≥ 70 mg/dl, who were statin-intolerant or taking a low-dose statin (≤ 10 mg per day of atorvastatin or an equivalent), received subcutaneous alirocumab 150 mg every 2 weeks. Carotid MRI was performed at baseline and 6 months after treatment, including pre- and post-contrast images for measuring percent lipid-core volume (%LC) and dynamic contrast-enhanced images for measuring microvessel leakiness (Ktrans), a marker of inflammation. Twenty-eight patients completed the study (69 ± 9 years; 64% male). Alirocumab led to significant changes in LDL-C (p < 0.001) and high-density lipoprotein cholesterol (HDL-C) (p = 0.003). At 6 months, there was a significant reduction in %LC (mean: − 2.1% [− 3.5, − 0.7], p = 0.005; a 17% reduction from baseline of 9.9%) without significant changes in lumen/wall area or in the inflammatory index Ktrans. Carotid plaque lipid content was reduced by 17% after 6 months of PCSK9 inhibition with alirocumab. This was seen before observable changes in lumen or wall areas, which supports pursing plaque lipid content as a more sensitive marker of therapeutic response compared to lumen or wall areas in future technical developments and serial studies.

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All data are available upon requests.

Abbreviations

ASCVD:

Atherosclerotic cardiovascular disease

CEA:

Carotid endarterectomy

DCE:

Dynamic contrast-enhanced

HDL-C:

High-density lipoprotein cholesterol

hsCRP:

High-sensitivity C-reactive protein

IPH:

Intraplaque hemorrhage

IQR:

Interquartile range

LDL-C:

Low-density lipoprotein cholesterol

LRNC:

Lipid-rich necrotic core

PCSK9:

Proprotein convertase subtilisin/kexin type 9

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Funding

Funded by an investigator-initiated grant from Regeneron and Sanofi.

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Authors and Affiliations

  1. University of Washington, 850 Republican St, Seattle, WA, 98109, USA

    Jie Sun, Gádor Cantón, Daniel S. Hippe, Daniel A. Isquith, Niranjan Balu, Chun Yuan, Xue-Qiao Zhao & Thomas S. Hatsukami

  2. Westside Medical Associates of Los Angeles, Beverly Hills, CA, USA

    Norman E. Lepor & Laurn Contreras

  3. Smidt Cedars-Sinai Heart Institute, Los Angeles, CA, USA

    Norman E. Lepor, Ilan Kedan & Americo A. Simonini

Authors
  1. Jie Sun
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  2. Norman E. Lepor
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  3. Gádor Cantón
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  5. Daniel S. Hippe
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  12. Thomas S. Hatsukami
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Contributions

(1) Study conception and design: JS, NEL, DSH, NB, CY, XQZ, TSH; (2) data acquisition: JS, NEL, GC, LC, DAI, IK, AAS; (3) data analysis: JS, DSH; (4) data interpretation: all authors; (5) manuscript preparation: JS, DSH; (6) manuscript revision: all authors; (7) approval of manuscript for submission: all authors.

Corresponding author

Correspondence to Jie Sun.

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Conflict of interest

Norman E. Lepor: Speakers bureau: Amgen, Sanofi, and Regeneron; Research support: The Medicines Company, Esperion, Amgen, Sanofi, and Regeneron. Daniel S. Hippe: Research support: GE Healthcare, Philips Healthcare, Toshiba America Medical Systems, Siemens Medical Solutions USA. Chun Yuan: Research support: Philips Healthcare. Xue-Qiao Zhao: Research support: Amgen, AstraZeneca. Thomas S. Hatsukami: Research support: Philips Healthcare. Other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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All study participants provided informed consent.

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Approved by the Western Institutional Review Board.

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Sun, J., Lepor, N.E., Cantón, G. et al. Serial magnetic resonance imaging detects a rapid reduction in plaque lipid content under PCSK9 inhibition with alirocumab. Int J Cardiovasc Imaging 37, 1415–1422 (2021). https://doi.org/10.1007/s10554-020-02115-w

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  • DOI: https://doi.org/10.1007/s10554-020-02115-w

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