Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction.

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).

• Authors: 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
• Journal: JACC. Cardiovascular imaging (JACC Cardiovasc Imaging) Vol. 15 Issue 7 Pg. 1308-1321 (07 2022) ISSN: 1876-7591 [Electronic] United States
• PMID: 35431172 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Anticholesteremic Agents
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• PCSK9 Inhibitors
• evolocumab

Topics

• Antibodies, Monoclonal, Humanized
• Anticholesteremic Agents (adverse effects)
• Cholesterol, LDL
• Coronary Artery Disease (diagnostic imaging, drug therapy)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects)
• Male
• Myocardial Infarction (diagnostic imaging, drug therapy)
• PCSK9 Inhibitors
• Phenotype
• Plaque, Atherosclerotic (drug therapy)
• Predictive Value of Tests
• Treatment Outcome