A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia

Study Questions:

What is the safety and efficacy of 52 weeks of treatment with evolocumab?

Methods:

The investigators stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4-12 weeks. Patients with low-density lipoprotein cholesterol (LDL-C) level of 75 mg/dl (1.9 mmol/L) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary endpoint was the percent change from baseline in LDL-C, as measured by means of ultracentrifugation, at week 52.

Results:

Among the 901 patients included in the primary analysis, the overall least-squares mean (± SE) reduction in LDL-C from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0 ± 2.1% (p < 0.001). The mean reduction was 55.7 ± 4.2% among patients who underwent background therapy with diet alone, 61.6 ± 2.6% among those who received 10 mg of atorvastatin, 56.8 ± 5.3% among those who received 80 mg of atorvastatin, and 48.5 ± 5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (p < 0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non–high-density lipoprotein cholesterol, lipoprotein (a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain.

Conclusions:

The authors concluded that at 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL-C levels in patients with a range of cardiovascular risks.

Perspective:

This study reports that treatment with 420 mg of evolocumab every 4 weeks for 52 weeks resulted in a relative reduction in LDL-C levels of 57%, taking into account the change in the placebo group. These findings were similar to the finding of a relative reduction of 52% in LDL-C levels reported in the first year of the OSLER (Open-Label Study of Long-Term Evaluation against LDL-C) study. PCSK9 inhibition with human monoclonal antibody appears to be an attractive strategy for individuals with suboptimal lipid control despite statins or those intolerant to statins.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Influenza, Human, Hyperlipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Back Pain, Heptanoic Acids, Pyrroles, Cholesterol, Azetidines, Cardiovascular Diseases, Diet, Nasopharyngitis, Triglycerides, ACC Annual Scientific Session


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