Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial.
Abstract | Importance: Objective: Design, Setting, and Participants: The GLAGOV multicenter, 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: Main Outcomes and Measures: The primary efficacy measure was 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, 92.5 mg/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 36.6 mg/dL; difference, -56.5 mg/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 0.9 mm3 with placebo and 5.8 mm3 with evolocumab (difference, -4.9 mm3 [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. Trial Registration: clinicaltrials.gov Identifier: NCT01813422.
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Authors | Stephen J Nicholls, Rishi Puri, Todd Anderson, Christie M Ballantyne, Leslie Cho, John J P Kastelein, Wolfgang Koenig, Ransi Somaratne, Helina Kassahun, Jingyuan Yang, Scott M Wasserman, Robert Scott, Imre Ungi, Jakub Podolec, Antonius Oude Ophuis, Jan H Cornel, Marilyn Borgman, Danielle M Brennan, Steven E Nissen |
Journal | JAMA
(JAMA)
Vol. 316
Issue 22
Pg. 2373-2384
(12 13 2016)
ISSN: 1538-3598 [Electronic] United States |
PMID | 27846344
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Cholesterol, LDL
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- PCSK9 Inhibitors
- PCSK9 protein, human
- evolocumab
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Topics |
- Antibodies, Monoclonal
(therapeutic use)
- Antibodies, Monoclonal, Humanized
- Cholesterol, LDL
(blood)
- Coronary Angiography
- Coronary Artery Disease
(blood, diagnostic imaging, drug therapy)
- Disease Progression
- Double-Blind Method
- Female
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(therapeutic use)
- Injections, Subcutaneous
- Male
- Middle Aged
- PCSK9 Inhibitors
- Placebo Effect
- Plaque, Atherosclerotic
(drug therapy, pathology)
- Remission Induction
- Time Factors
- Ultrasonography
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