***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: AIMS Mipomersen , an apolipoprotein ( apo ) B synthesis inhibitor , has been shown to produce potent reductions in apoB and LDL-cholesterol levels in animal models as well as healthy human volunteers . A r and omized , double-blind , placebo-controlled , dose-escalation study was design ed to evaluate the efficacy and safety of mipomersen monotherapy with or without dose loading in subjects with mild-to-moderate hyperlipidaemia . METHODS AND RESULTS Fifty subjects with LDL-cholesterol levels between 119 and 266 mg/dL were enrolled into five cohorts at a 4:1 r and omization ratio of active to placebo . Two 13-week dose regimens were evaluated at doses ranging from 50 to 400 mg/week . Mipomersen produced dose-dependent reductions in all apoB containing lipoproteins . In the 200 and 300 mg/week dose cohorts , mean reductions from baseline in LDL cholesterol were -45 ± 10 % ( P= 0.000 ) and -61 ± 8 % ( P= 0.000 ) , corresponding to a -46 ± 11 % ( P= 0.000 ) and -61 ± 7 % ( P= 0.000 ) decrease in apoB levels . Triglyceride levels were also lowered with median reductions up to 53 % ( P= 0.021 ) . The most common adverse events were injection site reactions . Seven of 40 subjects ( 18 % ) showed consecutive transaminase elevations > 3 × upper limit of normal . Five of these subjects received 400 mg/week , four of whom had apoB levels below the limit of detection . As a consequence , the 400 mg/week cohort was discontinued . CONCLUSIONS Mipomersen administered as monotherapy in subjects with mild-to-moderate hyperlipidaemia produced potent reductions in all apoB-containing lipoproteins . Higher doses were associated with hepatic transaminase increases BACKGROUND Homozygous familial hypercholesterolaemia is a genetic disorder characterised by substantially raised LDL cholesterol , reduced LDL receptor function , xanthomas , and cardiovascular disease before age 20 years . Conventional therapy is with statins , ezetimibe , and apheresis . We aim ed to assess the long-term safety and efficacy of the proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) inhibitor evolocumab in a subset of patients with homozygous familial hypercholesterolaemia enrolled in an open-label , non-r and omised phase 3 trial . METHODS In this interim subset analysis of the TAUSSIG study , which was undertaken at 35 sites in 17 countries , we included patients aged 12 years or older with homozygous familial hypercholesterolaemia who were on stable LDL cholesterol-lowering therapy for at least 4 weeks ; all patients received evolocumab 420 mg subcutaneously monthly , or if on apheresis every 2 weeks . Dosing could be increased to every 2 weeks after 12 weeks in patients not on apheresis . The primary outcome of the TAUSSIG study was treatment-emergent adverse events ; secondary outcomes were the effects of evolocumab on LDL cholesterol and other lipids . We analysed patients on an intention-to-treat basis , and all statistical comparisons were done post hoc in this interim analysis . The TAUSSIG study is registered with Clinical Trials.gov , number NCT01624142 , and is ongoing . FINDINGS 106 patients were included in this analysis , 34 receiving apheresis at study entry and 14 younger than 18 years . The first patient was enrolled on June 28 , 2012 , and the cutoff date for the analysis was Aug 13 , 2015 ; mean follow-up was 1·7 years ( SD 0·63 ) . After 12 weeks , mean LDL cholesterol decreased from baseline by 20·6 % ( SD 24·4 ; mean absolute decrease 1·50 mmol/L [ SD 1·92 ] ) ; these reductions were maintained at week 48 . 47 of 72 patients not on apheresis at study entry increased evolocumab dosing to every 2 weeks , with an additional mean reduction in LDL cholesterol of 8·3 % ( SD 13·0 ; mean absolute decrease 0·77 mmol/L [ SD 1·38 ] ; p=0·0001 ) . In a post-hoc analysis , mean reductions in LDL cholesterol in patients on apheresis were significant at week 12 ( p=0·0012 ) and week 48 ( p=0·0032 ) , and did not differ from reductions achieved in patients not on apheresis ( p=0·38 at week 12 and p=0·09 at week 48 ) . We noted a small reduction ( median -7·7 % [ IQR -21·6 to 6·8 ] ) in lipoprotein(a ) at week 12 ( p=0·0015 ) , with some additional reduction at week 48 ( -11·9 % [ -28·0 to 0·0 ] ; p<0·0001 ) . HDL cholesterol was increased by a mean of 7·6 % ( SD 18·1 ) at week 12 ( p<0·0001 ) and 7·6 % ( SD 20·6 ) at week 48 ( p=0·0007 ) . Evolocumab was well tolerated ; 82 ( 77 % ) patients reported treatment-emergent adverse events , which were mostly minor . The most common were nasopharyngitis ( 14 patients [ 13 % ] ) , influenza ( 13 [ 12 % ] ) , headache ( 11 [ 10 % ] ) , and upper respiratory tract infection ( 11 [ 10 % ] ) . Serious adverse events occurred in 18 ( 17 % ) patients , with the most common being cardiovascular events ( four patients [ 4 % ] ) . There were no deaths and four positively adjudicated cardiovascular events , one ( 3 % ) among patients on apheresis and three ( 4 % ) among patients who did not receive apheresis . INTERPRETATION Our interim results suggest that evolocumab is an effective additional option to reduce LDL cholesterol in patients with homozygous familial hypercholesterolaemia , with or without apheresis . FUNDING Amgen BACKGROUND Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs . We aim ed to assess the efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in adults with this disease . METHODS We did a single-arm , open-label , phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia . Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26 . Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day . The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26 , after which patients remained on lomitapide through to week 78 for safety assessment . Percent change from baseline to week 26 was assessed with a mixed linear model . FINDINGS 29 men and women with homozygous familial hypercholesterolaemia , aged 18 years or older , were recruited from 11 centres in four countries ( USA , Canada , South Africa , and Italy ) . 23 of 29 enrolled patients completed both the efficacy phase ( 26 weeks ) and the full study ( 78 weeks ) . The median dose of lomitapide was 40 mg a day . LDL cholesterol was reduced by 50 % ( 95 % CI -62 to -39 ) from baseline ( mean 8·7 mmol/L [ SD 2·9 ] ) to week 26 ( 4·3 mmol/L [ 2·5 ] ; p<0·0001 ) . Levels of LDL cholesterol were lower than 2·6 mmol/L in eight patients at 26 weeks . Concentrations of LDL cholesterol remained reduced by 44 % ( 95 % CI -57 to -31 ; p<0·0001 ) at week 56 and 38 % ( -52 to -24 ; p<0·0001 ) at week 78 . Gastrointestinal symptoms were the most common adverse event . Four patients had aminotransaminase levels of more than five times the upper limit of normal , which resolved after dose reduction or temporary interruption of lomitapide . No patient permanently discontinued treatment because of liver abnormalities . INTERPRETATION Our study suggests that treatment with lomitapide could be a valuable drug in the management of homozygous familial hypercholesterolaemia . FUNDING FDA Office of the Orphan Product Development , Aegerion Pharmaceuticals OBJECTIVES The aim of this study was to evaluate the efficacy and safety of mipomersen in hypercholesterolemic subjects taking stable statin therapy . BACKGROUND Mipomersen is an apolipoprotein ( apo ) B synthesis inhibitor that has demonstrated significant reductions in apo B and low-density lipoprotein ( LDL ) cholesterol in Phase 1 clinical trials in healthy volunteers . METHODS A r and omized , placebo-controlled , dose-escalation Phase 2 study was design ed to evaluate the effects of mipomersen in hypercholesterolemic subjects taking stable statin therapy . Seventy-four subjects were enrolled sequentially into 1 of 6 dose cohorts at a 4:1 ( active/placebo ) ratio . Subjects received 7 doses of 30 to 400 mg over 5 weeks in the first 5 cohorts and 15 doses of 200 mg over 13 weeks in the sixth cohort . Pre-specified end points included percentage change from baseline in apo B and LDL cholesterol . Safety was assessed with laboratory test results and by the incidence and severity of adverse events . RESULTS The apo B and LDL cholesterol were reduced by 19 % to 54 % and 21 % to 52 % , respectively , at doses of 100 mg/week mipomersen and higher in the 5-week treatment cohorts . Efficacy seemed to increase upon treatment for 13 weeks at a dose of 200 mg/week . Injection site reactions ( mild to moderate erythema [ 90 % ] ) and hepatic transaminase increases ( 17 % ) were the most common adverse events , leading to discontinuation in 2 subjects and 1 subject , respectively . In the 13-week treatment cohort , 5 of 10 subjects ( 50 % ) had elevations > or=3x the upper limit of normal , 4 of which persisted on 2 consecutive occasions . CONCLUSIONS Mipomersen might hold promise for treatment of patients not reaching target LDL cholesterol levels on stable statin therapy . Further studies are needed to address the mechanisms and clinical relevance of transaminase changes after mipomersen administration . ( Dose-Escalating Safety Study in Subjects on Stable Statin Therapy ; NCT00231569 ) Background Routine apolipoprotein ( apo ) measurements for cardiovascular disease ( CVD ) are restricted to apoA-I and apoB. Here , the authors measured an unprecedented range of apolipoproteins in a prospect i ve , population -based study and relate their plasma levels to risk of CVD . Objectives This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level underst and ing of the correlations of apolipoproteins with the plasma lipidome and proteome . Methods Associations of 13 apolipoproteins , 135 lipid species , and 211 other plasma proteins with incident CVD ( 91 events ) , defined as stroke , myocardial infa rct ion , or sudden cardiac death , were assessed prospect ively over a 10-year period in the Bruneck Study ( N = 688 ) using multiple-reaction monitoring mass spectrometry . Changes in apolipoprotein and lipid levels following treatment with volanesorsen , a second-generation antisense drug targeting apoC-III , were determined in 2 human intervention trials , one of which was r and omized . Results The apolipoproteins most significantly associated with incident CVD were apoC-II ( hazard ratio per 1 SD [ HR/SD ] : 1.40 ; 95 % confidence interval [ CI ] : 1.17 to 1.67 ) , apoC-III ( HR/SD : 1.38 ; 95 % CI : 1.17 to 1.63 ) , and apoE ( HR/SD : 1.31 ; 95 % CI : 1.13 to 1.52 ) . Associations were independent of high-density lipoprotein ( HDL ) and non-HDL cholesterol , and extended to stroke and myocardial infa rct ion . Lipidomic and proteomic profiles implicated these 3 very-low-density lipoprotein (VLDL)-associated apolipoproteins in de novo lipogenesis , glucose metabolism , complement activation , blood coagulation , and inflammation . Notably , 
    Output:
    
As a matter of fact , mipomersen therapy is more likely discontinued and associated with increased risk of injection-site reactions , hepatic steatosis , hepatic enzyme elevation , and flu-like symptoms