Effect of Evolocumab on Coronary Plaque Composition

J Am Coll Cardiol. 2018 Oct 23;72(17):2012-2021. doi: 10.1016/j.jacc.2018.06.078.

Abstract

Background: Incremental low-density lipoprotein (LDL) cholesterol lowering with the proprotein convertase subtilisin kexin type 9 inhibitor evolocumab regresses coronary atherosclerosis in statin-treated patients.

Objectives: The purpose of this study was to evaluate the effect of adding evolocumab to statin therapy on coronary plaque composition.

Methods: A total of 968 statin-treated coronary artery disease patients underwent serial coronary intravascular ultrasound imaging at baseline and following 76 weeks of treatment with placebo or evolocumab 420 mg monthly. Plaque composition changes were determined in 331 patients with evaluable radiofrequency analysis of the ultrasound backscatter signal.

Results: Compared with statin monotherapy, evolocumab further reduced LDL cholesterol (33.5 mg/dl vs. 89.9 mg/dl; p < 0.0001) and induced regression of percent atheroma volume (-1.2% vs. +0.17%; p < 0.0001) and total atheroma volume (-3.6 mm3 vs. -0.8 mm3; p = 0.04). No difference was observed between the evolocumab and placebo groups in changes in calcium (1.0 ± 0.3 mm3 vs. 0.6 ± 0.3 mm3; p = 0.49), fibrous (-3.0 ± 0.6 mm3 vs. -2.4 ± 0.6 mm3; p = 0.49), fibrofatty (-5.0 ± 1.0 mm3 vs. -3.0 ± 1.0 mm3; p = 0.49), and necrotic (-0.6 ± 0.5 mm3 vs. -0.1 ± 0.5 mm3; p = 0.49) volumes. An inverse correlation was observed between changes in LDL cholesterol and plaque calcification (r = -0.15; p < 0.001).

Conclusions: The addition of evolocumab to a statin did not produce differential changes in plaque composition compared with statin monotherapy. This suggests that evaluation of plaque morphology using virtual histology imaging may provide no incremental information about the plaque effects of evolocumab beyond measurement of plaque burden. (GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound [GLAGOV]; NCT01813422).

Keywords: PCSK9; atherosclerosis; clinical trial; imaging; lipids.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents / administration & dosage
  • Cholesterol, LDL / metabolism
  • Coronary Artery Disease* / diagnosis
  • Coronary Artery Disease* / drug therapy
  • Coronary Artery Disease* / metabolism
  • Drug Monitoring / methods
  • Drug Therapy, Combination / methods
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Male
  • Middle Aged
  • PCSK9 Inhibitors*
  • Plaque, Atherosclerotic* / diagnostic imaging
  • Plaque, Atherosclerotic* / drug therapy
  • Plaque, Atherosclerotic* / metabolism
  • Treatment Outcome
  • Ultrasonography, Interventional / methods*

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01813422