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Evolocumab and Coronary Plaque Composition
Study Questions:
What is the effect of adding evolocumab to statin therapy on coronary plaque composition?
Methods:
The investigators assessed 968 statin-treated coronary artery disease patients with 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 low-density lipoprotein cholesterol (LDL-C) (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-C and plaque calcification (r = -0.15; p < 0.001).
Conclusions:
The authors concluded that addition of evolocumab to a statin did not produce differential changes in plaque composition compared with statin monotherapy.
Perspective:
This study reports that the administration of evolocumab to statin-treated patients with coronary artery disease produced robust reductions in LDL-C and regression of coronary atherosclerosis, but did not produce any significant difference in plaque composition compared with statin monotherapy using virtual histology. This suggests that evaluation of plaque morphology using virtual histology imaging may not provide any incremental information about the plaque effects of evolocumab beyond measurement of plaque burden. An ongoing study (NCT03689946) assessing the effect of evolocumab on coronary plaque composition by coronary computed tomography angiography and microcalcification by F18 sodium fluoride positron emission tomography will provide insight on the role of alternative imaging modalities in assessing plaque morphology and composition, and whether these modalities are able to detect any changes.
Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging
Keywords: Antibodies, Monoclonal, Atherosclerosis, Cholesterol, LDL, Coronary Angiography, Coronary Artery Disease, Diagnostic Imaging, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Plaque, Atherosclerotic, Secondary Prevention, Ultrasonography
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