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 .
Efficacy and safety of evolocumab in individuals with type 2 diabetes mellitus: primary results of the randomised controlled BANTING study
Aims /hypothesisThe study aim ed to examine the efficacy of 12 weeks of monthly evolocumab or placebo in lowering LDL-cholesterol ( LDL-C ) in individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia and on a maximum-tolerated statin of at least moderate intensity . Methods For this r and omised , placebo-controlled outpatient study , eligible individuals were ≥18 years old with type 2 diabetes , HbA1c < 10 % ( 86 mmol/mol ) , had been on stable pharmacological therapy for diabetes for ≥6 months and were taking a maximum-tolerated statin dose of at least moderate intensity . Lipid eligibility criteria varied by history of clinical cardiovascular disease . Participants were r and omised 2:1 to evolocumab 420 mg s.c . or placebo .  R and omisation was performed central ly via an interactive web-based or voice recognition system . Allocation was concealed using the central ised r and omisation process . Treatment assignment was blinded to the sponsor study team , investigators , site staff and patients throughout the study . Co- primary endpoints were mean percentage change in LDL-C from baseline to week 12 and to the mean of weeks 10 and 12 . Additional endpoints included LDL-C < 1.81 mmol/l , LDL-C reduction ≥50 % and other lipids . Exploratory analyses included percentage changes in fasting and post mixed-meal tolerance test ( MMTT ) lipoproteins and lipids , glucose metabolism variables and inflammatory biomarkers . Results In total , 421 individuals were r and omised and analysed , having received evolocumab ( 280 participants ) or placebo ( 141 participants ) ( mean [ SD ] age 62 [ 8 ] years ; 44 % women ; 77 % white ) . Evolocumab decreased LDL-C by 54.3 % ( 1.4 % ) at week 12 ( vs 1.1 % [ 1.9 % ] decrease with placebo ; p < 0.0001 ) and by 65.0 % ( 1.3 % ) at the mean of weeks 10 and 12 ( vs 0.8 % [ 1.8 % ] decrease with placebo ; p < 0.0001 ) ; it also decreased non-HDL-cholesterol ( HDL-C ) by 46.9 % ( 1.3 % ) at week 12 ( vs 0.6 % [ 1.8 % ] decrease with placebo ) and by 56.6 % ( 1.2 % ) at the mean of weeks 10 and 12 ( vs 0.1 % [ 1.6 % ] decrease with placebo ) . Evolocumab significantly improved levels of other lipids and allowed more participants to reach LDL-C < 1.81 mmol/l or a reduction in LDL-C levels ≥50 % . After an MMTT ( 120 min ) , there were favourable changes ( p < 0.05 ; nominal , post hoc , no multiplicity adjustment ) in chylomicron triacylglycerol ( triglycerides ) , chylomicron cholesterol , VLDL-C and LDL-C. Evolocumab had no effect on glycaemic variables and was well tolerated . Conclusions /interpretationIn statin-treated individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia , evolocumab significantly reduced LDL-C and non-HDL-C. Favourable changes ( p < 0.05 ) were observed in postpr and ial levels of chylomicrons , VLDL-C and LDL-C.Trial registration Clinical Trials.gov NCT02739984 Funding This study was funded by Amgen Inc. Data availabilityQualified research ers may request data from Amgen clinical studies . Complete details are available at www.amgen.com/ data sharing
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 .