Effect of Evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocardial infarction

Stephen J. Nicholls, Yu Kataoka, Steven E. Nissen, Francesco Prati, Stephan Windecker, Rishi Puri, Thomas Hucko, Daniel Aradi, Jean Paul R. Herrman, Renicus S. Hermanides, Bei Wang, Huei Wang, Julie Butters, Giuseppe Di Giovanni, Stephen Jones, Gianluca Pompili, Peter J. Psaltis

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83 Citations (Scopus)

Abstract

Background: The proprotein convertase subtilisin kexin type-9 inhibitor evolocumab produced coronary atheroma regression in statin-treated patients. Objectives: The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition. Methods: Patients with a non–ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated. Results: Among treated patients (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol [LDL-C], 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 μm; P = 0.015) and decrease in maximum lipid arc (−57.5o vs. −31.4o; P = 0.04) and macrophage index (−3.17 vs −1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (−2.29% ± 0.47% vs −0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium. Conclusions: The combination of statin and evolocumab after a non–ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697)

Original languageEnglish
Pages (from-to)1308-1321
Number of pages14
JournalJACC: Cardiovascular Imaging
Volume15
Issue number7
DOIs
Publication statusAccepted/In press - 16 Mar 2022

Keywords

  • PCSK9 inhibitor
  • acute coronary syndromes
  • atherosclerosis
  • clinical trials
  • lipid lowering

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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