AHA 2016: Evolocumab treatment associated with significant regression of atherosclerosis
After 76 weeks of treatment, patients with symptomatic coronary artery disease who received evolocumab plus statin therapy had a statistically significant regression of atherosclerosis compared with patients who received statins and a placebo, according to a randomized trial.
All of the patients in the study presented with clinically indicated coronary angiography.
Lead researcher Steven E. Nissen, MD, of the Cleveland Clinic, presented the results in a late-breaking clinical trials session at the American Heart Association Scientific Sessions in New Orleans.
The findings were simultaneously published online in JAMA on Nov. 15. Amgen, which manufactures evolocumab (Repatha), funded the study.
The FDA approved evolocumab in August 2015 for adults with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of low-density lipoprotein (LDL) cholesterol. Evolocumab is an injectable proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor.
In this trial, known as GLAGOV, the researchers enrolled 968 patients from May 3, 2013, to Jan. 12, 2015, at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia and South Africa.
All patients underwent coronary angiography and then had an intravascular ultrasound (IVUS) performed at baseline. They were then randomized in a 1:1 ratio to receive monthly doses of 420 mg of evolocumab or placebo for 76 weeks. All patients also received statins.
During the study, patients had clinic visits at weeks four, 12, 24, 36, 52, 64 and 76. At week 78, they had another IVUS.
In all, 846 patients (423 in each group) underwent IVUS at baseline and week 78. The mean exposure to the study drug was 17.6 months.
At baseline, the mean LDL cholesterol level was 92.5 mg/dL, while 58.9 percent of patients were receiving high-intensity statin therapy, 39.4 percent were receiving moderate-intensity therapy and 1.4 percent were not receiving statins. The mean age was approximately 60 years old, and approximately 72 percent of the patients were males.
During the treatment period, the time-weighted mean LDL cholesterol levels were 93.0 mg/dL in the placebo group and 36.6 mg/dL in the evolocumab group.
“Based on previous studies, we did not know if GLAGOV would show additional plaque regression at LDL [cholesterol] levels below 60 mg/dL,” study author Stephen J. Nicholls, MBBS, PhD, said in a news release. “One of the most compelling results from GLAGOV is the continued reduction of plaque at LDL [cholesterol] levels well below commonly accepted thresholds.”
Patients who received evolucumab also had greater reductions in levels of apolipoprotein B, triglycerides and lipoprotein (a) and greater increased in levels of high-density lipoprotein cholesterol. The median high-sensitivity C-reactive protein levels were 1.4 mg/L in each group.
During the study, the atheroma volume did not change in the placebo group and decreased by 0.95 percent in the evolocumab group. In addition, 47.3 percent and 64.3 percent of patients, respectively, had a regression in atheroma volume.
Meanwhile, the total atheroma volume did not change in the placebo group and decreased by 5.8 mm3 in the evolocumab group. Further, 48.9 percent and 61.5 percent of patients, respectively, had a regression in total atheroma volume.
“These findings provide evidence that PCSK9 inhibition produces incremental benefits on coronary disease progression in statin-treated patients,” the researchers wrote.
An exploratory subgroup analysis of patients with a baseline LDL cholesterol level of less than 70 mg/dL found that those who received evolocumab had a 58.3 percent reduction in LDL cholesterol after 80 weeks of treatment. The patients in the evolocumab group also had 1.97 percent decrease in atheroma volume, while 81.2 percent had a regression in total atheroma volume.
“We have never seen levels of regression at that magnitude in any study previously conducted,” Nissen said during a news conference. “It’s really quite extraordinary.”
Nissen said the study was too small to show an effect of evolocumab on cardiovascular morbidity and mortality and to assess the drug’s safety. However, the event rates with regards to first major cardiovascular events, neurocognitive events, new onset diabetes and myalgia were similar in the evolocumab and placebo groups.
“IVUS is a useful measure of disease activity, but the critical determination of benefit and risk is going to come from the outcomes trials,” Nissen said. “We are very humble about this. We know we have a surrogate endpoint. We think this is a signal that suggest that there may be benefits at really low LDL levels, but the definitive studies will come hopefully next year.”
Executive Editor
Tim Casey joined TriMed Media Group in 2015 as Executive Editor. For the previous four years, he worked as an editor and writer for HMP Communications, primarily focused on covering managed care issues and reporting from medical and health care conferences. He was also a staff reporter at the Sacramento Bee for more than four years covering professional, college and high school sports. He earned his undergraduate degree in psychology from the University of Notre Dame and his MBA degree from Georgetown University.