Stephen J Nicholls1, Yu Kataoka2, Steven E Nissen3, Francesco Prati4, Stephan Windecker5, Rishi Puri3, Thomas Hucko6, Daniel Aradi7, Jean-Paul R Herrman8, Renicus S Hermanides9, Bei Wang6, Huei Wang6, Julie Butters10, Giuseppe Di Giovanni11, Stephen Jones11, Gianluca Pompili11, Peter J Psaltis12. 1. Victorian Heart Institute, Monash University, Clayton, Australia. Electronic address: stephen.nicholls@monash.edu. 2. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Suita, Japan. 3. Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA. 4. San Giovanni Hospital, UniCamillus "Saint Camillus International University of Health Science," Rome, Italy. 5. Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland. 6. Global Development, Amgen Inc, Thousand Oaks, California, USA. 7. Heart and Vascular Center, University of Semmelweis, Budapest, Hungary; Heart Center Balatonfüred, Balatonfüred, Hungary; Tagore Medical Center, Balatonfüred, Hungary. 8. OLVG Oost, Amsterdam, the Netherlands. 9. Isala Hospital, Department of Cardiology, Zwolle, the Netherlands. 10. Victorian Heart Institute, Monash University, Clayton, Australia. 11. South Australian Health and Medical Research Institute, Adelaide, Australia. 12. South Australian Health and Medical Research Institute, Adelaide, Australia; Adelaide Medical School, University of Adelaide, Department of Cardiology, Central Adelaide Local Health Network, Adelaide, Australia.
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).
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: Lorenz Räber; Yasushi Ueki; Tatsuhiko Otsuka; Sylvain Losdat; Jonas D Häner; Jacob Lonborg; Gregor Fahrni; Juan F Iglesias; Robert-Jan van Geuns; Anna S Ondracek; Maria D Radu Juul Jensen; Christian Zanchin; Stefan Stortecky; David Spirk; George C M Siontis; Lanja Saleh; Christian M Matter; Joost Daemen; François Mach; Dik Heg; Stephan Windecker; Thomas Engstrøm; Irene M Lang; Konstantinos C Koskinas Journal: JAMA Date: 2022-05-10 Impact factor: 157.335