IMPORTANCE Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on coronary atherosclerosis have not been evaluated. OBJECTIVE To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients. DESIGN, SETTING,ANDPARTICIPANTS TheGLAGOVmulticenter, double-blind, placebo-controlled, randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia, and South Africa and enrolling 968 patients presenting for coronary angiography. INTERVENTIONS Participants with angiographic coronary disease were randomized to receive monthly evolocumab (420mg) (n = 484) or placebo (n = 484) via subcutaneous injection for 76 weeks, in addition to statins. MAIN OUTCOMES AND MEASURES The primary efficacy measurewas the nominal change in percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. RESULTS Among the 968 treated patients (mean age, 59.8 years [SD, 9.2]; 269 [27.8%] women; mean LDL-C level, 92.5mg/dL [SD, 27.2]), 846 had evaluable imaging at follow-up. Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C levels (93.0 vs 36.6mg/dL; difference, -56.5mg/dL [95%CI, -59.7 to -53.4]; P < .001). The primary efficacy parameter, PAV, increased 0.05%with placebo and decreased 0.95%with evolocumab (difference, -1.0% [95%CI, -1.8%to -0.64%]; P < .001). The secondary efficacy parameter, normalized TAV, decreased 0.9mm3 with placebo and 5.8mm3 with evolocumab (difference, -4.9mm3 [95%CI, -7.3 to -2.5]; P < .001). Evolocumab induced plaque regression in a greater percentage of patients than placebo (64.3%vs 47.3%; difference, 17.0%[95%CI, 10.4%to 23.6%]; P < .001 for PAV and 61.5%vs 48.9%; difference, 12.5% [95%CI, 5.9% to 19.2%]; P < .001 for TAV). CONCLUSIONS AND RELEVANCE Among patients with angiographic coronary disease treated with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes.