Discussion
We found that treatment with 420 mg of evolocumab every 4 weeks for 52 weeks resulted in a relative reduction in LDL cholesterol levels of 57%, taking into account the change in the placebo group. This result was consistent with the effects that were observed with the same evolocumab regimen in the 12-week phase 2 trials.3-6 In addition, we found no decrement in the efficacy of evolocumab from week 12 to week 52. Our findings were also similar to the finding of a relative reduction of 52% in LDL cholesterol levels reported in the first year of the Open-Label Study of Long-Term Evaluation against LDL-C (OSLER) study.10 Our study design called for a run-in period in which background lipid-lowering therapy was adjusted on the basis of LDL cholesterol goals, according to the patient’s ATP-III–defined cardiovascular risk. These risk-based lipid-lowering therapies ranged from diet alone to a combination of 80 mg of atorvastatin plus 10 mg of the cholesterol-absorption inhibitor ezetimibe daily. Percent reductions in LDL cholesterol in the evolocumab group, taking into account the change in the placebo group, differed slightly according to background therapy, ranging from 48.5% in the group receiving atorvastatin plus ezetimibe to 61.6% in the group receiving 10 mg of atorvastatin. Our findings provide some insights into the magnitude and duration of PCSK9 inhibition with antibodies as a function of background lipid-lowering therapy. In our study, unbound PCSK9 was measured at 1 week and at 4 weeks after the administration of evolocumab. The dif