The reduction in MACEs was observed in White but not in Asian subjects .
Both alirocumab and evolocumab are well tolerated and can greatly improve lipid profiles for patients at high cardiovascular risk .
Both PCSK9 monoclonal antibodies significantly reduce the risk of nonfatal MACEs in patients with previous cardiovascular events , but the effect on all-cause mortality remains uncertain
Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) monoclonal antibodies are powerful lipid-lowering drugs which have been shown to improve clinical endpoints in patients with hypercholesterolemia .
However , it is not clear how effective PCSK9 monoclonal antibodies are for patients at high cardiovascular risk .
Also , whether the effectiveness of PCSK9 monoclonal antibodies varies between different drug types , dosages , race , and indications for PCSK9 monoclonal antibodies remains unclear .
Therefore , we used recently published studies to systematic ally evaluate the efficacy and safety of PCSK9 monoclonal antibodies by analyzing the lipid profiles , adverse events , and clinical endpoints in patients at high cardiovascular risk .
PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial
BACKGROUND Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol , increased plasma LDL cholesterol concentrations , and premature cardiovascular disease . Despite intensive statin therapy , with or without ezetimibe , many patients are unable to achieve recommended target levels of LDL cholesterol . We investigated the effect of PCSK9 inhibition with evolocumab ( AMG 145 ) on LDL cholesterol in patients with this disorder . METHODS This multicentre , r and omised , double-blind , placebo-controlled trial was undertaken at 39 sites ( most of which were specialised lipid clinics , mainly attached to academic institutions ) in Australia , Asia , Europe , New Zeal and , North America , and South Africa between Feb 7 and Dec 19 , 2013 . 331 eligible patients ( 18 - 80 years of age ) , who met clinical criteria for heterozygous familial hypercholesterolaemia and were on stable lipid-lowering therapy for at least 4 weeks , with a fasting LDL cholesterol concentration of 2·6 mmol/L or higher , were r and omly allocated in a 2:2:1:1 ratio to receive subcutaneous evolocumab 140 mg every 2 weeks , evolocumab 420 mg monthly , or subcutaneous placebo every 2 weeks or monthly for 12 weeks . R and omisation was computer generated by the study sponsor , implemented by a computerised voice interactive system , and stratified by LDL cholesterol concentration at screening ( higher or lower than 4·1 mmol/L ) and by baseline ezetimibe use ( yes/no ) . Patients , study personnel , investigators , and Amgen study staff were masked to treatment assignments within dosing frequency groups . The co primary endpoints were percentage change from baseline in LDL cholesterol at week 12 and at the mean of weeks 10 and 12 , analysed by intention-to-treat . This trial is registered with Clinical Trials.gov , number NCT01763918 . FINDINGS Of 415 screened patients , 331 were eligible and were r and omly assigned to the four treatment groups : evolocumab 140 mg every 2 weeks ( n=111 ) , evolocumab 420 mg monthly ( n=110 ) , placebo every 2 weeks ( n=55 ) , or placebo monthly ( n=55 ) . 329 patients received at least one dose of study drug . Compared with placebo , evolocumab at both dosing schedules led to a significant reduction in mean LDL cholesterol at week 12 ( every-2-weeks dose : 59·2 % reduction [ 95 % CI 53·4 - 65·1 ] , monthly dose : 61·3 % reduction [ 53·6 - 69·0 ] ; both p<0·0001 ) and at the mean of weeks 10 and 12 ( 60·2 % reduction [ 95 % CI 54·5 - 65·8 ] and 65·6 % reduction [ 59·8 - 71·3 ] ; both p<0·0001 ) . Evolocumab was well tolerated , with rates of adverse events similar to placebo . The most common adverse events occurring more frequently in the evolocumab-treated patients than in the placebo groups were nasopharyngitis ( in 19 patients [ 9 % ] vs five [ 5 % ] in the placebo group ) and muscle-related adverse events ( ten patients [ 5 % ] vs 1 [ 1 % ] ) . INTERPRETATION In patients with heterozygous familial hypercholesterolaemia  , evolocumab administered either 140 mg every 2 weeks or 420 mg monthly was well tolerated and yielded similar and rapid 60 % reductions in LDL cholesterol compared with placebo . FUNDING Amgen
The reduction in MACEs was observed in White but not in Asian subjects .
Both alirocumab and evolocumab are well tolerated and can greatly improve lipid profiles for patients at high cardiovascular risk .
Both PCSK9 monoclonal antibodies significantly reduce the risk of nonfatal MACEs in patients with previous cardiovascular events , but the effect on all-cause mortality remains uncertain
Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) monoclonal antibodies are powerful lipid-lowering drugs which have been shown to improve clinical endpoints in patients with hypercholesterolemia .
However , it is not clear how effective PCSK9 monoclonal antibodies are for patients at high cardiovascular risk .
Also , whether the effectiveness of PCSK9 monoclonal antibodies varies between different drug types , dosages , race , and indications for PCSK9 monoclonal antibodies remains unclear .
Therefore , we used recently published studies to systematic ally evaluate the efficacy and safety of PCSK9 monoclonal antibodies by analyzing the lipid profiles , adverse events , and clinical endpoints in patients at high cardiovascular risk .