25773607
BACKGROUND	Evolocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) , significantly reduced low-density lipoprotein ( LDL ) cholesterol levels in short-term studies .
BACKGROUND	We conducted two extension studies to obtain longer-term data .
METHODS	In two open-label , randomized trials , we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ( `` parent trials '' ) of evolocumab .
METHODS	Regardless of study-group assignments in the parent trials , eligible patients were randomly assigned in a 2:1 ratio to receive either evolocumab ( 140 mg every 2 weeks or 420 mg monthly ) plus standard therapy or standard therapy alone .
METHODS	Patients were followed for a median of 11.1 months with assessment of lipid levels , safety , and ( as a prespecified exploratory analysis ) adjudicated cardiovascular events including death , myocardial infarction , unstable angina , coronary revascularization , stroke , transient ischemic attack , and heart failure .
METHODS	Data from the two trials were combined .
RESULTS	As compared with standard therapy alone , evolocumab reduced the level of LDL cholesterol by 61 % , from a median of 120 mg per deciliter to 48 mg per deciliter ( P < 0.001 ) .
RESULTS	Most adverse events occurred with similar frequency in the two groups , although neurocognitive events were reported more frequently in the evolocumab group .
RESULTS	The risk of adverse events , including neurocognitive events , did not vary significantly according to the achieved level of LDL cholesterol .
RESULTS	The rate of cardiovascular events at 1 year was reduced from 2.18 % in the standard-therapy group to 0.95 % in the evolocumab group ( hazard ratio in the evolocumab group , 0.47 ; 95 % confidence interval , 0.28 to 0.78 ; P = 0.003 ) .
CONCLUSIONS	During approximately 1 year of therapy , the use of evolocumab plus standard therapy , as compared with standard therapy alone , significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis .
CONCLUSIONS	( Funded by Amgen ; OSLER-1 and OSLER-2 ClinicalTrials.gov numbers , NCT01439880 and NCT01854918 . )

