Home > General Cardiology, Journal Club > Journal Club 11 June 2014

Journal Club 11 June 2014

Paper

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

Presenter

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Summary

Background

Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/
kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol
levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and
efficacy of 52 weeks of treatment with evolocumab.

Methods

We 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 to 12 weeks. Patients with an LDL
cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then
randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo
every 4 weeks. The primary end point was the percent change from baseline in LDL
cholesterol, 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 cholesterol 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

At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to highdose
atorvastatin with or without ezetimibe significantly reduced LDL cholesterol
levels in patients with a range of cardiovascular risks.

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