In patients with angiographic coronary disease who have been treated with a statin, the addition of evolocumab, a PCSK9 inhibitor, led to greater low-density lipoprotein cholesterol (LDL-C) lowering and atheroma regression compared with placebo after 76 weeks of treatment, according to a study in JAMA.
Stephen J. Nicholls, MBBS, PhD, from the University of Adelaide in Australia, and colleagues conducted the double-blind, placebo-controlled, randomized GLAGOV trial at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia, and South Africa. Between May 3, 2013, and January 12, 2015, 968 patients presented for coronary angiography and were enrolled in the study.
The participants were randomly assigned to receive monthly evolocumab (420 mg) (n=484) or placebo (n=484) via subcutaneous injection for 76 weeks, in addition to statin therapy. The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to week 78, as 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. The investigators also evaluated safety and tolerability.
The participants had a mean age of 59.8 years, 269 (27.8%) were women, and the mean LDL-C level was 92.5 mg/dL. A total of 846 had evaluable imaging at follow-up. Compared with placebo, those who received evolocumab had lower mean, time-weighted LDL-C levels (93.0 vs 36.6 mg/dL, respectively). PAV increased 0.05% with placebo and decreased 0.95% with evolocumab. Normalized TAV decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab. Evolocumab induced plaque regression in a greater percentage of patients compared with placebo (64.3% vs 47.3%, respectively, for PAV and 61.5% vs 48.9%, respectively, for TAV).
“These findings provide evidence that PCSK9 inhibition produces incremental benefits on coronary disease progression in statin-treated patients,” the researchers stated.
- Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016; Nov 15. doi: 10.1001/jama.2016.16951.