***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Purpose Even with statins and other lipid-lowering therapy ( LLT ) , many patients with heterozygous familial hypercholesterolemia ( heFH ) continue to have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . ODYSSEY HIGH FH ( NCT01617655 ) assessed the efficacy and safety of alirocumab , a proprotein convertase subtilisin/kexin type 9 monoclonal antibody , versus placebo in patients with heFH and LDL-C ≥ 160 mg/dl despite maximally tolerated statin ± other LLT . Methods Patients were r and omized to subcutaneous alirocumab 150 mg or placebo every 2 weeks ( Q2W ) for 78 weeks . The primary endpoint was percent change in LDL-C from baseline to week 24 . Results Mean baseline LDL-C levels were 196.3 mg/dl in the alirocumab ( n = 71 ) and 201.0 mg/dl in the placebo groups ( n = 35 ) . Significant mean ( st and ard error [ SE ] ) reductions in LDL-C from baseline to week 24 were observed with alirocumab ( −45.7 [ 3.5 ] % ) versus placebo ( −6.6 [ 4.9 ] % ) , a difference of −39.1 ( 6.0 ) % ( P < 0.0001 ) . Absolute mean ( SE ) LDL-C levels were reduced from baseline by 90.8 ( 6.7 ) mg/dl with alirocumab at week 24 , with reductions maintained to week 78 . Treatment-emergent adverse events were generally comparable between groups . Injection-site reactions were more frequent in the alirocumab group ( 8.3 % ) versus placebo ( 5.7 % ) ; most were mild in severity and did not result in study medication discontinuation . Conclusions In patients with heFH and very high LDL-C baseline levels despite maximally tolerated statin ± other LLT , alirocumab 150 mg Q2W demonstrated significant reductions in LDL-C levels with 41 % of patients achieving predefined LDL-C goals . Alirocumab was generally well tolerated BACKGROUND Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy . METHODS In a Phase 3 , r and omized , double-blind , double-dummy study ( NCT01644474 ) , patients ( low-density lipoprotein cholesterol [ LDL-C ] 100 - 190 mg/dL , 10-year risk of fatal cardiovascular events ≥ 1%-<5 % [ systemic coronary risk estimation ] ) were r and omized  to ezetimibe 10mg/day ( n=51 ) or alirocumab 75 mg subcutaneously ( via 1-mL autoinjector ) every 2 weeks ( Q2W ) ( n=52 ) , with dose up-titrated to 150 mg Q2W ( also 1 mL ) at week 12 if week 8 LDL-C was ≥ 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks , analyzed using all available data ( intent-to-treat approach , ITT ) . Analyses using on-treatment LDL-C values were also conducted . RESULTS Mean ( SD ) baseline LDL-C levels were 141.1 ( 27.1 ) mg/dL ( alirocumab ) and 138.3 ( 24.5 ) mg/dL ( ezetimibe ) . The 24-week treatment period was completed by 85 % of alirocumab and 86 % of ezetimibe patients . Least squares mean ( SE ) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe ( ITT ; p<0.0001 ) and 54 (2)% versus 17 (2)% ( on-treatment ; p<0.0001 ) . At week 12 , before up-titration , alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% ( on-treatment ) . Injection site reactions were infrequent ( < 2 % and < 4 % of alirocumab and ezetimibe patients , respectively ) . CONCLUSIONS Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50 % LDL-C reduction in the majority of the patients . Adverse events were comparable between groups BACKGROUND AND AIMS In previous phase III studies , the PCSK9 monoclonal antibody alirocumab was administered at doses of 75 or 150 mg every 2 weeks ( Q2W ) . CHOICE I ( NCT01926782 ) evaluated 300 mg every 4 weeks ( Q4W ) in patients on either maximally  tolerated statin  or no statin , both ± other lipid-lowering therapies . METHODS CHOICE I included patients with hypercholesterolemia at moderate-to-very-high cardiovascular risk . Patients were r and omized to alirocumab 300 mg Q4W , 75 mg Q2W ( calibrator arm ) , or placebo for 48 weeks , with dose adjustment for either alirocumab arm to 150 mg Q2W at Week ( W ) 12 if at W8 LDL-C levels were > 70/100 mg/dL ( 1.8/2.6 mmol/L ) depending on cardiovascular risk or LDL-C reduction was < 30 % from baseline . Co- primary endpoints were percent LDL-C change from baseline to W24 , and to time-averaged LDL-C over W21 - 24 . RESULTS Approximately two-thirds of r and omized patients were receiving statins . At W12 , 14.7 % ( no statin ) and 19.3 % ( statin ) of patients receiving alirocumab 300 mg Q4W required dose adjustment . At W24 , significant LDL-C reductions from baseline were observed with alirocumab 300 mg Q4W : mean differences were -52.7 % ( no statin ; placebo : -0.3 % ) and -58.8 % ( statin ; placebo : -0.1 % ) . Average LDL-C reductions from baseline to W21 - 24 were also significantly greater with alirocumab 300 mg Q4W vs. placebo in patients not receiving ( -56.9 % vs. -1.6 % ) and receiving statin ( -65.8 % vs. -0.8 % ) . Treatment-emergent adverse event rates ranged from 61.1 to 75.0 % ( placebo ) and 71.5 to 78.1 % ( alirocumab 300 mg Q4W ) . CONCLUSIONS Alirocumab 300 mg Q4W is a viable additional treatment option in patients requiring LDL-C-lowering Aims Statins have modest adverse effects on glycaemic control .  Alirocumab , a proprotein convertase subtilisin/kexin type 9 inhibitor , lowers low-density lipoprotein cholesterol . This study assessed the effects of alirocumab on  new-onset diabetes and pre-diabetes incidence in individuals without diabetes at baseline . Methods and results Pooled analysis of 10 ODYSSEY Phase 3 trials ( n = 4974 ) of 24–104 weeks duration . Six trials ( n = 4211 ) were ≥52 weeks in length . Most patients received background maximally tolerated statin . Alirocumab effect on the rate of diabetes-related treatment-emergent adverse events ( TEAEs ) , and /or fasting plasma glucose ( FPG ) and glycated haemoglobin A1C ( HbA1C ) was measured at baseline and every 12–24 weeks . Transition to diabetes analysis combined TEAE and FPG/HbA1C laboratory data . At baseline , 30.7 % of individuals had diabetes and were excluded from the current analysis . The remaining 3448 individuals without diabetes had pre-diabetes ( 39.6 % ) or were normoglycaemic ( 29.7 % ) . The hazard ratio ( HR ; 95 % confidence interval ) for diabetes-related TEAEs in alirocumab was 0.64 ( 0.36–1.14 ) vs. placebo and 0.55 ( 0.22–1.41 ) vs. ezetimibe . The HR associated for transition from pre-diabetes to new-onset diabetes for alirocumab was 0.90 ( 0.63–1.29 ) vs. placebo and 1.10 ( 0.57–2.12 ) vs. ezetimibe  . Mean change in FPG/HbA1C over time showed no difference between treatment groups in patients without diabetes . Conclusions There was no evidence of an effect of alirocumab  on transition to new-onset diabetes in 3448 individuals without diabetes at baseline with a follow-up period of 6–18 months , compared to either placebo or ezetimibe . Longer follow-up with larger number of individuals is needed to conclusively rule out an effect Aims To assess long-term ( 78 weeks ) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia ( HeFH ) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy ( LLT ) . Methods and results In two r and omized , double-blind studies ( ODYSSEY FH I , n = 486 ; FH II , n = 249 ) , patients were r and omized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks ( Q2W ) . Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L ( 70 mg/dL ) . Primary endpoint ( both studies ) was percentage change in calculated LDL-C from baseline to Week 24 . Mean LDL-C levels decreased from 3.7 mmol/L ( 144.7 mg/dL ) at baseline to 1.8 mmol/L ( 71.3 mg/dL ; −57.9 % vs. placebo ) at Week 24 in patients r and omized to alirocumab in FH I and from 3.5 mmol/L ( 134.6 mg/dL ) to 1.8 mmol/L ( 67.7 mg/dL ; −51.4 % vs. placebo ) in FH II ( P < 0.0001 ) . These reductions were maintained through Week 78 . LDL-C < 1.8 mmol/L ( regardless of cardiovascular risk ) was achieved at Week 24 by 59.8 and 68.2 % of alirocumab-treated patients in FH I and FH II , respectively . Adverse events result ed in discontinuation in 3.4 % of alirocumab-treated patients in FH I ( vs. 6.1 % placebo ) and 3.6 % ( vs. 1.2 % ) in FH II . Rate of injection site reactions  in alirocumab-treated patients was 12.4 % in FH I and 11.4 % in FH II ( vs. 11.0 and 7.4 % with placebo ) . Conclusion In patients with HeFH and inadequate LDL-C control at baseline despite maximally tolerated statin ± other LLT , alirocumab treatment result ed in significant LDL-C lowering and greater achievement of LDL-C target levels and was well tolerated . Clinical trial registration Cinicaltrials.gov ( identifiers : NCT01623115 ; NCT01709500 ) CONTEXT Despite current st and ard of care , many patients at high risk of cardiovascular disease ( CVD ) still have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . Alirocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 . OBJECTIVE The objective of the study was to compare the LDL-C-lowering efficacy of adding alirocumab vs other common lipid-lowering strategies . DESIGN , PATIENTS , AND INTERVENTIONS Patients ( n = 355 ) with very high CVD risk and LDL-C levels of 70 mg/dL or greater or high CVD risk and LDL-C of 100 mg/dL or greater on baseline atorvastatin 20 or 40 mg were r and omized to one of the following : 1 ) add-on alirocumab 75 mg every 2 weeks ( Q2W ) sc ; 2 ) add-on ezetimibe 10 mg/d ; 3 ) double atorvastatin dose ; or 4 ) for atorvastatin 40 mg regimen only , switch to ro 
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Meta-regression analyses showed that risk of NODM was not associated with baseline age , baseline body mass index ( BMI ) , proportion of men , treatment duration or percent LDL cholesterol reduction .
CONCLUSIONS Alirocumab and evolocumab , two types of PCSK9-mAb approved by the US Food and Drug Administration and the European Medicines Agency , had no significant impact on NODM and glucose homeostasis , regardless of PCSK9-mAb type , participant characteristics , treatment duration , treatment method and differences in control treatment .
Baseline age , BMI , proportion of men , treatment duration , and percent change of LDL cholesterol did not influence diabetes risk