Effect of Evolocumab on Coronary Plaque Composition

• Published in: Journal of the American College of Cardiology Vol. 72; no. 17; pp. 2012 - 2021
• Main Authors: Nicholls, Stephen J., Puri, Rishi, Anderson, Todd, Ballantyne, Christie M., Cho, Leslie, Kastelein, John J.P., Koenig, Wolfgang, Somaratne, Ransi, Kassahun, Helina, Yang, Jingyuan, Wasserman, Scott M., Honda, Satoshi, Shishikura, Daisuke, Scherer, Daniel J., Borgman, Marilyn, Brennan, Danielle M., Wolski, Kathy, Nissen, Steven E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.10.2018; Elsevier Limited
• Subjects: Aged; Antibodies, Monoclonal - administration & dosage; Anticholesteremic Agents - administration & dosage; Arteriosclerosis; Atherosclerosis; Backscattering; Calcification; Calcification (ectopic); Calcium; Cardiology; Cardiovascular disease; Cholesterol; Cholesterol, LDL - metabolism; clinical trial; Composition; Coronary artery; Coronary artery disease; Coronary Artery Disease - diagnosis; Coronary Artery Disease - drug therapy; Coronary Artery Disease - metabolism; Coronary vessels; Drug Monitoring - methods; Drug Therapy, Combination - methods; Female; Heart diseases; Histology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; imaging; Kexin; lipids; Low density lipoprotein; Male; Medical imaging; Middle Aged; Monoclonal antibodies; Morphology; Patients; PCSK9; Plaque, Atherosclerotic - diagnostic imaging; Plaque, Atherosclerotic - drug therapy; Plaque, Atherosclerotic - metabolism; Proprotein Convertase 9 - antagonists & inhibitors; Proprotein convertases; Radio frequency; Statins; Statistical analysis; Studies; Subtilisin; Treatment Outcome; Ultrasonic imaging; Ultrasonography, Interventional - methods; Ultrasound; Veins & arteries; United States > US; California; atherosclerosis; clinical trial; CRP; lipids; VH; PAV; LDL; TAV; PCSK9; IVUS; imaging
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2018.06.078

Incremental low-density lipoprotein (LDL) cholesterol lowering with the proprotein convertase subtilisin kexin type 9 inhibitor evolocumab regresses coronary atherosclerosis in statin-treated patients. The purpose of this study was to evaluate the effect of adding evolocumab to statin therapy on coronary plaque composition. 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. 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). 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) [Display omitted]