The effect on PCSK9 levels that we observed and the consequent reductions in LDL cholesterol levels at 4 weeks after the administration of evolocumab were similar to those reported in patients receiving either 10 mg or 80 mg of atorvastatin plus another PCSK9 monoclonal antibody, alirocumab (at a dose of 150 mg), even though patients received alirocumab every 2 weeks rather than every 4 weeks.7 Thus, it may be that patients who have already been treated with high-dose statins or combination lipid-lowering therapy may have slightly less capacity to further up-regulate LDL-receptor activity with PCSK9 inhibition or may require higher doses of antibody. Our findings are also in keeping with those of a number of other trials in which no synergism between statins and PCSK9 inhibition was observed. Although statins up-regulate PCSK9, this does not explain why the reduction in LDL cholesterol levels that is associated with an initial dose of a statin is relatively large in comparison to the additional 6% reduction observed when the statin dose is doubled.