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 high-dose atorvastatin with or without ezetimibe 
significantly reduced LDL cholesterol levels in patients with a range of 
cardiovascular risks. (Funded by Amgen; DESCARTES ClinicalTrials.gov number, 
NCT01516879.).