***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 Hypercholesterolemia coexisting with diabetes still requires clinical intervention to manage the high risk of cardiovascular disease it poses . No second-step strategy is established , however , for cases where strong statins fail to bring cholesterol down to target levels . In this study we seek to demonstrate the superior effect of ezetimibe in combination with strong statins to reduce LDL-C in Japanese patients suffering from both T2DM and hyper LDL-cholesterolemia . Methods T2DM out patients ( 109 patients from 16 institutes ) who failed to achieve the target LDL-C value were recruited and r and omly assigned to two groups , a double-dose-statin group and ezetimibe-plus-statin group . Follow-ups were scheduled at 0 , 12 , 26 , and 52 weeks . The primary endpoint was the percentage change in the level of LDL-C from baseline to 12 weeks . Interim results We could successfully create r and omized ( gender , age , LDL-C , HbA1c , etc . ) two groups except for slight differences in apolipoprotein-B and sd-LDL . Conclusions RESEARCH is the first prospect i ve , parallel-group , multicenter study comparing a double dose of strong statin with ezetimibe plus strong statin for T2DM patients . The RESEARCH study will provide reliable evidence with which to establish a clinical strategy for diabetics who fail to achieve the target LDL-C value Summary : Sixty-two patients ( 34 men and 28 women ) aged 19–64 years , half of whom had familial hypercholesterolemia , treated initially for 18 weeks with lovastatin alone  were r and omly allocated either to lovastatin ( L ) and cholestyramine ( 16 g/day ) or lovastatin and guar gum ( L + GG 20 g/day ) treatment for 18 additional weeks to compare the hypocholesterolemic effects of these two combination therapies . The patients were selected for this study from a larger study of patients ( n = 120 ) with severe hypercholesterolemia [ serum total cholesterol ( serum Chol ) 6.5–16.3 mM before treatment ] , and only those patients in whom serum Chol after lovastatin alone ( dose 80 mg/day ) remained ≥5.2 mM were eligible for evaluation of combination therapies . Serum Chol decreased from 10.6 × 1.6 to 5.9 = 1.3 mM ( mean × SD ) ( p < 0.001 ) and low-density lipoprotein cholesterol ( LDL Chol ) from 8.5 × 1.8 to 4.1 × 1 mM ( p < 0.001 ) in patients treated with L + GG ( values before the beginning of lovastatin and at the end of the combination therapy ) . The respective changes were from 10.9 × 2.2 to 5.5 × 1.2 mM ( p < 0.001 ) and from 8.7 × 2.3 to 3.5 × 1.2 mM ( p < 0.001 ) in patients treated with lovastatin and cholestyramine ( L + C ) . At the end of the study , both serum Cho ) ( p < 0.005 ) and LDL Chol ( p < 0.01 ) were significantly lower with L + C than with L + GG . After the combination of L + GG or L + C , the additional reductions in serum Chol and LDL Chol levels were 0.98 mM ( 0.62–1.3 mM , 95 % confidence interval , CI ) and 0.92 mM ( 0.56–1.3 mM ) for the L + GG group and 1.5 mM ( 1.1–1.9 mM ) and 1.6 mM ( 1.2–2.0 mM ) for the L + C group , respectively . Apoprotein B was similarly reduced in both groups , but no significant changes were noted in lipoprotein ( a ) or apoprotein Al levels . The combination of lovastatin with cholestyramine was more effective in decreasing serum Chol levels in patients with familial hypercholesterolemia , whereas no significant difference in efficacy was noted in nonfamilial cases The phase 3 ODYSSEY OPTIONS studies ( OPTIONS I , NCT01730040 ; OPTIONS II , NCT01730053 ) are multicenter , multinational , r and omized , double‐blind , active‐comparator , 24‐week studies evaluating the efficacy and safety of alirocumab , a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 , as add‐on therapy in ∼ 650 high‐cardiovascular (CV)‐risk patients whose low‐density lipoprotein cholesterol ( LDL‐C ) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV‐risk category , high and very high CV risk , respectively , with atorvastatin ( 20–40 mg/d ) or rosuvastatin ( 10–20 mg/d ) . Patients are r and omized to receive alirocumab 75 mg via a single , subcutaneous , 1‐mL injection by prefilled pen every 2 weeks ( Q2W ) as add‐on therapy to atorvastatin ( 20–40 mg ) or rosuvastatin ( 10–20 mg ) ; or to receive ezetimibe 10 mg/d as add‐on therapy to statin ; or to receive statin up‐titration ; or to switch from atorvastatin to rosuvastatin ( OPTIONS I only ) . At week 12 , based on week 8 LDL‐C levels , the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL‐C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk , respectively . The primary efficacy endpoint in both studies is difference in percent change in calculated LDL‐C from baseline to week 24 in the alirocumab vs control arms . The studies may provide guidance to inform clinical decision‐making when patients with CV risk require additional lipid‐lowering therapy to further reduce LDL‐C levels . The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL‐C reduction required to achieve the desired LDL‐C level Background Individuals with heterozygous familial hypercholesterolemia ( heFH ) have higher levels of low-density lipoprotein cholesterol ( LDL-C ) and are predisposed to premature cardiovascular disease . Alirocumab is a fully-human , monoclonal antibody targeted to proprotein convertase subtilisin/kexin type 9 currently in Phase 3 development for the treatment of hypercholesterolemia . Described here are three ODYSSEY Phase 3 trials , FH I ( NCT01623115 ) , FH II ( NCT01709500 ) and HIGH FH ( patients with heFH and LDL-C levels ≥160 mg/dL ) ( NCT01617655 ) , in which alirocumab is further evaluated in the heFH population . Methods Multicenter , multinational , r and omized , double-blind , placebo-controlled studies have been design ed to evaluate efficacy and safety  of alirocumab in more than 800 patients with heFH who are not adequately controlled with a maximally-tolerated stable daily dose of statin for ≥4 weeks prior to the screening visit , with or without other lipid-lowering therapy . Patients are r and omized ( 2:1 ) to receive alirocumab or placebo via a 1-mL subcutaneous auto-injection every 2 weeks ( Q2W ) for 78 weeks . In studies FH I and II , if their Week 8 LDL-C level is ≥70 mg/dL , patients will undergo a dose uptitration from 75 to 150 mg alirocumab Q2W at Week 12 . In HIGH FH , patients will receive alirocumab 150 mg Q2W throughout the entire treatment period . The primary efficacy endpoint in all three studies is the percent change in calculated LDL-C from baseline to Week 24 . Conclusions The ODYSSEY FH studies are three Phase 3 studies aim ing to further evaluate the efficacy and long-term safety of alirocumab as an effective therapeutic option for patients with heFH Bococizumab is a humanized monoclonal antibody binding proprotein convertase subtilisin/kexin type 9 , which may be a potential therapeutic option for reducing low-density lipoprotein cholesterol ( LDL-C ) levels in patients with hypercholesterolemia . In this 24-week , multicenter , double-blind , placebo-controlled , dose-ranging study ( NCT01592240 ) , subjects with LDL-C levels≥80 mg/dl on stable statin therapy were r and omized to Q14 days  subcutaneous placebo or bococizumab 50 , 100 , or 150 mg or Q28 days subcutaneous placebo or bococizumab 200 or 300 mg . Doses of bococizumab were reduced if LDL-C levels persistently decreased to ≤25 mg/dl . The primary end point was the absolute change in LDL-C levels from baseline to week 12 after placebo or bococizumab administration . Continuation of bococizumab administration through to week 24 enabled the collection of safety data over an extended period . Of the 354 subjects r and omized , 351 received treatment  ( placebo [ n=100 ] or bococizumab [ n=251 ] ) . The most efficacious bococizumab doses were 150 mg Q14 days and 300 mg Q28 days . Compared with placebo , bococizumab 150 mg Q14 days reduced LDL-C at week 12 by 53.4 mg/dl and bococizumab 300 mg Q28 days reduced LDL-C by 44.9 mg/dl ; this was despite dose reductions in 32.5 % and 34.2 % of subjects at week 10 or 8 , respectively . Pharmacokinetic/pharmacodynamic model-based simulation assuming no dose reductions predicted that bococizumab would lower LDL-C levels by 72.2 and 55.4 mg/dl , respectively . Adverse events were similar across placebo and bococizumab groups . Few subjects ( n=7 ; 2 % ) discontinued treatment because of treatment-related adverse events . In conclusion , bococizumab significantly reduced LDL-C across all doses despite dose reductions in many subjects . Model-based simulations predicted greater LDL-C reduction in the absence of bococizumab dose reduction . The Q14 days regimen is being evaluated in phase 3 clinical trials Patients with mixed hyperlipidemia and at high risk of coronary heart disease may not achieve recommended low-density lipoprotein ( LDL ) and non-high-density lipoprotein ( non-HDL ) cholesterol goals on statin monotherapy . This study was design ed to evaluate the efficacy and safety of a fenofibrate 160 mg/pravastatin 40 mg fixed-dose combination therapy in high-risk patients not at their LDL cholesterol goal on pravastatin 40 mg . In this 12-week , multicenter , r and omized , double-blind , double-dummy , parallel-group study , after a run-in on pravastatin 40 mg , 248 patients were r and omly assigned to fenofibrate/pravastatin combination therapy or to pravastatin monotherapy . Combination therapy produced significantly greater complementary decreases in non-HDL cholesterol ( primary end point ) than pravastatin monotherapy ( -14.1 % vs -6.1 % , p = 0.002 ) . Significantly greater improvements were also observed in LDL cholesterol ( -11.7 % vs -5.9 % , p = 0.019 ) , HDL cholesterol ( + 6.5 % vs + 2.3 % , p = 0.009 ) , triglycerides ( -22.6 % vs -2.0 % , p = 0.006 ) , and apolipoprotein B ( -12.6 % vs -3.8 % , p < 0.0001 ) . Significantly more patients receiving the fenofibrate/pravastatin combination therapy than pravastatin alone achieved the LDL cholesterol ( < 100 mg/dl ) and non-HDL cholesterol ( < 130 mg/dl ) goals ( p < 0.01 ) . Combination therapy was generally well tolerated with incidences of clinical and laboratory adverse experiences similar between the 2 groups . In conclusion , the fenofibrate 160 mg/pravastatin 40 mg fixed-dose combination therapy significantly improved the global atherogenic lipid profile  in high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy BACKGROUND Present guidelines emphasise the importance of low concentrations of LDL cholesterol ( LDL-C ) in patients with familial hypercholesterolaemia . In most patients with the disease , however , these concentrations are not achieved with present treatments 
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Adverse events were similar between PCSK9 inhibitors and control .
Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe .
PCSK9 inhibitors added to medium- to high-intensity statin therapy significantly reduce LDL-C in patients requiring further LDL-C reduction .
The network meta- analysis showed a significant treatment difference in LDL-C reduction  for evolocumab versus alirocumab