Effects of ezetimibe on remnant-like particle cholesterol, lipoprotein (a), and oxidized low-density lipoprotein in patients with dyslipidemia. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Ezetimibe alone and in combination lowers the concentration of small, dense low-density lipoproteins in type 2 diabetes mellitus. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease. Effects of ezetimibe on plasma lipoproteins in severely hypercholesterolemic patients treated with regular LDL-apheresis and statins. Lipid-lowering effects of ezetimibe for hypercholesterolemic patients with and without type 2 diabetes mellitus. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. The Effect of Adding Ezetimibe to Rosuvastatin on Renal Function in Patients Undergoing Elective Vascular Surgery The effects of ezetimibe and orlistat, alone or in combination, on high-density lipoprotein (HDL) subclasses and HDL-associated enzyme activities in overweight and obese patients with hyperlipidaemia. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia. Ezetimibe effectively decreases LDL-cholesterol in HIV-infected patients Differences in action of atorvastatin and ezetimibe in lowering low-density lipoprotein cholesterol and effect on endothelial function: randomized controlled trial.
AIM Ezetimibe is a novel cholesterol absorption inhibitor that reduces the level of low-density lipoprotein (LDL)-cholesterol ( C ) . The effects of ezetimibe on remnant-like particle (RLP)-C , lipoprotein ( a ) [ Lp(a ) ] , and oxidized LDL ( Ox-LDL ) levels have not been examined . METHODS Fifty patients with dyslipidemia were treated with 10 mg/day of ezetimibe . At baseline and 12 weeks after treatment with ezetimibe , we measured the levels of RLP-C , Lp(a ) , Ox-LDL , and high-sensitivity C-reactive protein ( hs-CRP ) . RESULTS The mean levels of total cholesterol ( TC ) , LDL-C , triglycerides ( TG ) , and apolipoprotein ( apo ) B , respectively , showed a significant decrease from 229+/-39 to 191+/-37 mg/dL ( -16 % , p<0.0001 ) , from 151+/-34 to 118+/-33 mg/dL ( -22 % , p<0.0001 ) , from 162+/-82 to 135+/-55 mg/dL ( -7 % , p<0.01 ) , and from 116+/-22 to 94+/-21 mg/dL ( -18 % , p<0.0001 ) after 12 weeks of treat-ment with ezetimibe . The mean level of RLP-C and median level of hs-CRP also decreased signifi-cantly from 6.8+/-4.0 to 4.8+/-2.5 mg/dL ( -21 % , p<0.0001 ) and from 0.6 to 0.4 mg/L ( -33 % , p<0.05 ) . The median level of Lp(a ) decreased significantly from 14 to 10 mg/dL ( -29 % , p<0.05 ) in patients treated with ezetimibe monotherapy . CONCLUSIONS Ezetimibe was effective for reducing the levels of TC , LDL-C , TG , and RLP-C.  Ezeti-mibe could be a potential therapeutic option for decreasing the Lp(a ) level BACKGROUND Ezetimibe ( SCH 58235 ) is a novel cholesterol absorption inhibitor that selectively and potently blocks intestinal absorption of dietary and biliary cholesterol . OBJECTIVE Data from 2 multicenter , placebo-controlled , double-blind , r and omized , parallel-group , 12-week studies of ezetimibe were pooled to evaluate the drug 's effect on lipid parameters in patients with primary hypercholesterolemia . METHODS After dietary stabilization ( National Cholesterol Education Program Step I diet or a stricter diet ) , washout of lipid-altering drugs , and a 6-week placebo lead-in period , patients with baseline plasma low-density lipoprotein cholesterol ( LDL-C ) levels > or = 130 and < or = 250 mg/dL and plasma triglyceride ( TG ) levels < or = 300 mg/dL were r and omized to receive either ezetimibe 0.25 , 1 , 5 , or 10 mg , or placebo administered once daily before the morning meal in study A ( dose-response study ) or ezetimibe 5 or 10 mg or placebo administered once daily before the morning meal or at bedtime in study B ( dose-regimen study ) . RESULTS A total of 432 patients were included in this pooled analysis , 243 in study A and 189 in study B. The 5- and 10-mg doses of ezetimibe significantly reduced LDL-C levels by 15.7 % and 18.5 % , respectively ( P < 0.01 vs placebo ) and significantly increased high-density lipoprotein cholesterol ( hDL-C ) levels by 2.9 % and 3.5 % , respectively ( P < 0.05 vs placebo ) . A reduction in plasma TG levels was observed ( P = NS ) . With the 10-mg dose of ezetimibe , 67.8 % of patients achieved > or = 15 % reduction in plasma LDL-C levels , and 22.0 % achieved > or = 25 % reduction . With the 5-mg dose , 54.0 % of patients achieved > or = 15 % reduction in plasma LDL-C levels , and 15.3 % achieved > or = 25 % reduction . The decrease in plasma LDL-C levels was significantly greater with ezetimibe 10 mg compared with ezetimibe 5 mg ( P < 0.05 ) . Ezetimibe was well tolerated , with an adverse event profile similar to that of placebo . CONCLUSIONS In these two 12-week studies , ezetimibe significantly decreased plasma LDL-C levels and increased plasma HDL-C levels , with a tolerability profile similar to that of placebo The efficacy and safety of ezetimibe , a new cholesterol absorption inhibitor , was evaluated in this r and omized , double-blind , placebo-controlled trial of 892 patients with primary hypercholesterolemia . After > or = 2 weeks on the National Cholesterol Education Program ( NCEP ) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in , patients with low-density lipoprotein ( LDL ) cholesterol 130 to 250 mg/dl and triglycerides < or = 350 mg/dl were r and omized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks . The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point . A total of 434 men and 458 women ( ages 18 to 85 years ) received r and omized treatment ( 666 ezetimibe 10 mg , 226 placebo ) . Demographics and baseline characteristics were similar between treatment groups . Ezetimibe significantly reduced direct LDL cholesterol by a mean of 16.9 % , compared with an increase of 0.4 % with placebo ( p < 0.01 ) . Subgroup analysis indicated that response to ezetimibe was generally consistent across all subgroups , regardless of risk-factor status , gender , age , race , or baseline lipid profile . Ezetimibe effects on LDL cholesterol occurred early ( 2 weeks ) and persisted throughout the 12-week treatment period . Compared with placebo , ezetimibe 10 mg also significantly improved calculated LDL cholesterol , apolipoprotein B , total cholesterol , triglycerides , high-density lipoprotein ( HDL ) cholesterol , and HDL(3 ) cholesterol ( p < 0.01 ) . Ezetimibe was well tolerated . There were no differences in laboratory or clinical safety parameters , or gastrointestinal , liver , or muscle side effects from that of placebo . Ezetimibe 10 mg/day is well tolerated , reduces LDL cholesterol approximately 17 % , and improves other key lipid parameters OBJECTIVE The effectiveness of the cholesterol absorption inhibitor ezetimibe on LDL subfractions and ultimately on the atherosclerotic risk profile remains controversial . We thus determined the concentration of atherogenic small , dense LDL ( sdLDL ) in patients with type 2 diabetes and an elevated cardiovascular risk profile . RESEARCH DESIGN AND METHODS Multicenter , r and omized , open-label 6-week study investigating the effect of ezetimibe 10 mg ( E ) , simvastatin 20 mg ( S ) and the combination of ezetimibe-/simvastatin 10/20 mg ( C ) on the concentration of sdLDL separated from fresh plasma by gradient ultracentrifugation in patients with type 2 diabetes ( NCT01384058 ) . RESULTS Fifty-six patients were screened for sdLDL , 41 were r and omized , and 40 patients ( 12 E , 14 S and 14 C ) completed the study .  Total and LDL cholesterol fell by 14 % ( p=0.004 ) and 15 % ( p=0.006 ) with E , 22 % ( p<0.001 ) and 32 % ( p<0.001 ) with S , and 32 % ( p<0.001 ) and 44 % ( p<0.001 ) with C , respectively . E reduced the concentration of sdLDL by 20 % ( p=0.043 ) whereas S and C reduced sdLDL by 24 % ( p=0.020 ) and 33 % ( p=0.003 ) , respectively , and non-sdLDL by 28 % ( p=0.004 ) and 42 % ( p<0.001 ) , respectively . However , the further drop in sdLDL by adding E to S was not significant . CONCLUSION Ezetimibe alone and in combination with simvastatin reduced the concentration of atherogenic sdLDL in patients with type 2 diabetes IMPORTANCE In phase 2 studies , evolocumab , a fully human monoclonal antibody to PCSK9 , reduced LDL-C levels in patients receiving statin therapy . OBJECTIVE To evaluate the efficacy and tolerability of evolocumab when used in combination with a moderate- vs high-intensity statin . DESIGN , SETTING , AND PATIENTS Phase 3 , 12-week , r and omized , double-blind , placebo- and ezetimibe-controlled study conducted between January and December of 2013 in patients with primary hypercholesterolemia and mixed dyslipidemia at 198 sites in 17 countries . INTERVENTIONS Patients ( n = 2067 ) were r and omized to 1 of 24 treatment groups in 2 steps . Patients were initially r and omized to a daily , moderate-intensity ( atorvastatin [ 10 mg ] , simvastatin [ 40 mg ] , or rosuvastatin [ 5 mg ] ) or high-intensity ( atorvastatin [ 80 mg ] , rosuvastatin [ 40 mg ] ) statin . After a 4-week lipid-stabilization period , patients ( n = 1899 ) were r and omized to compare evolocumab ( 140 mg every 2 weeks or 420 mg monthly ) with placebo ( every 2 weeks or monthly ) or ezetimibe ( 10 mg or placebo daily ; atorvastatin patients only ) when added to statin therapies . MAIN OUTCOMES AND MEASURES Percent change from baseline in low-density lipoprotein cholesterol ( LDL-C ) level at the mean of weeks 10 and 12 and at week 12 . RESULTS Evolocumab  reduced LDL-C levels by 66 % ( 95 % CI , 58 % to 73 % ) to 75 % ( 95 % CI , 65 % to 84 % ) ( every 2 weeks ) and by 63 % ( 95 % CI , 54 % to 71 % ) to 75 % ( 95 % CI , 67 % to 83 % ) ( monthly ) vs placebo at the mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups ; the LDL-C reductions at week 12 were comparable . For moderate-intensity statin groups , evolocumab every 2 weeks reduced LDL-C from a baseline mean of 115 to 124 mg/dL to an on-treatment mean of 39 to 49 mg/dL ; monthly evolocumab reduced LDL-C from a baseline mean of 123 to 126 mg/dL to an on-treatment mean of 43 to 48 mg/dL. For high-intensity statin groups , evolocumab every 2 weeks reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 35 to 38 mg/dL ; monthly evolocumab reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 33 to 35 mg/dL. Adverse events were reported in 36 % , 40 % , and 39 % of evolocumab- , ezetimibe- , and placebo-treated patients , respectively . The most common adverse events in evolocumab-treated patients were back pain , arthralgia , headache , muscle spasms , and pain in extremity ( all < 2 % ) . CONCLUSIONS AND RELEVANCE In this 12-week trial conducted among patients with primary hypercholesterolemia and mixed dyslipidemia , evolocumab added to moderate- or high-intensity statin therapy result ed in additional LDL-C lowering . Further studies are needed to evaluate the longer-term clinical outcomes and safety of this approach for LDL-C lowering . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01763866 Background This study was performed to compare the effects of three different lipid-lowering therapies ( statins , ezetimibe , and colestimide ) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma ( pre-heparin LPL and EL mass , respectively ) from patients with familial hypercholesterolemia ( FH ) . FH is usually treated by coadministration of these three drugs . Methods The pre-heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored at various time points during coadministration of the three drugs from patients with heterozygous FH harboring a single mutation in the LDL receptor ( n = 16 , mean age 63 years ) . The patients were r and omly divided into two groups based on the timing when ezetimibe was added . Results Plasma LPL mass concentration was significantly reduced by rosuvastatin at 20 mg/day ( median = 87.4 [ IQR : 71.4–124.7 ] to 67.5 [ IQR : 62.1–114.3 ] ng/ml , P < 0.05 ) . In contrast , ezetimibe at 10 mg/day as well as colestimide at 3.62 g/day did not alter its level substantially ( median = 67.5 [ IQR : 62.1–114.3 ] to 70.2 [ IQR : 58.3–106.2 ] , and to 74.9 [ IQR : 55.6–101.3 ] ng/ml , respectively ) in the group starting with rosuvastatin followed by the addition of ezetimibe and colestimide . On the other h and , the magnitude in LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day before reaching the maximum dose of 20 mg/day of rosuvastatin . Plasma EL mass concentration was significantly increased by rosuvastatin at 20 mg/day ( median = 278.8 [ IQR : 186.7–288.7 ] to 297.0 [ IQR : 266.2–300.2 ] ng/ml , P < 0.05 ) , whereas other drugs did not significantly alter its level . Conclusion The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy , which may impact the prevention of atherosclerosis differently This r and omised , double-blind , placebo (PBO)-controlled study evaluated the efficacy and safety of ezetimibe ( EZE ) co-administered with ongoing atorvastatin ( ATV ) therapy in 450 hypercholesterolemic patients with coronary heart disease ( CHD ) who had not achieved their low-density lipoprotein cholesterol ( LDL-C ) goal < or = 2.60 mmol/l while on a stable dose of ATV 10 or 20 mg/day for > or = 6 weeks . After a 4-week diet/baseline active run-in period , patients with LDL-C > 2.60 mmol/l and < or = 4.20 mmol/l were stratified by ATV dose and r and omised ( 1 : 1 ) to EZE 10 mg or PBO for 6 weeks while continuing open-label ATV . Significantly more patients achieved an LDL-C goal < or = 2.6 mmol/l with EZE than PBO ( 81.3 vs. 21.8 % ; p < or = 0.001 ) . Compared to PBO , co-administration of EZE with ongoing ATV led to significantly ( p < or = 0.001 ) greater reductions in LDL-C , total cholesterol , triglycerides , non-high-density lipoprotein cholesterol ( non-HDL-C ) , and apolipoprotein B ; HDL-C was significantly ( p < or = 0.05 ) increased . Co-administration of EZE and ATV was well tolerated , with an overall safety profile similar to ATV alone Ezetimibe , a cholesterol absorption inhibitor , can be combined with statins to lower LDL-cholesterol . We evaluated additional ezetimibe ( 10 mg/day ) in a placebo-controlled , double blind , r and omized cross-over study in 20 patients ( age 56+/-9 years , m : f 10:10 , BMI 27.5+/-4.0 kg/m(2 ) ) suffering from severe hypercholesterolemia and CHD who were treated by statins and regular LDL-apheresis .  Lipoproteins ( cholesterol , triglycerides , LDL-cholesterol , HDL-cholesterol , VLDL-cholesterol , VLDL-triglycerides , lipoprotein(a ) ) were determined twice ( before and during ezetimibe/placebo , each given for 5 weeks ) , dietary behaviour was analyzed once ( 3-days- protocol ) during each treatment period . During ezetimibe the mean ( + /-S.D. ) preapheresis LDL-cholesterol concentration decreased from 159+/-26 mg/dl ( 4.11+/-0.67 mmol/l ) to 133+/-28 mg/dl ( 3.44+/-0.72 mmol/l ) ( -16+/-11 % , P<0.0001 , Wilcoxon test ) and the postapheresis LDL-cholesterol from 51+/-9 mg/dl ( 1.32+/-0.23 mmol/l ) to 43+/-8 mg/dl ( 1.11+/-0.21 mmol/l ) ( -14+/-25 % , P<0.05 ) , while there was no significant change during placebo .  Mean VLDL-cholesterol fell by 18+/-71 % ( P<0.05 ) during ezetimibe and was not significantly changed by placebo ( + 19+/-70 % ) . Furthermore , during ezetimibe less plasma volume was treated ( 3725+/-1560 versus 3870+/-1549 ml , P<0.05 ) . Ezetimibe had no effect on pre- and postapheresis triglyceride , HDL-cholesterol and lipoprotein(a ) levels . The effect of ezetimibe was independent of the statin dose . Dietary behaviour did not change and no side effects were observed . Thus , in patients with severe LDL-hypercholesterolemia and CHD the addition of ezetimibe to intensive lipid lowering therapy ( statins and LDL-apheresis ) result ed in a further , clinical ly significant decrease of LDL-cholesterol To date , there are very few clinical reports that have compared the effects of ezetimibe on lipid parameters between hypercholesterolemic patients with and without type 2 diabetes mellitus ( T2DM ) . In this study , we recruited patients for hypercholesterolemic groups with T2DM ( n = 42 ; men/women = 24/18 ; HbA1c = 6.7 ± 5.4 % ) and without T2DM ( n = 21 ; men/women = 7/14 ; HbA1c = 5.3 ± 0.4 % ) . Patients were prescribed ezetimibe at a dose of 10 mg/daily for the course of the 12-week study . At baseline and after 12 weeks of treatment , several lipid parameters , including serum low-density-lipoprotein cholesterol ( LDL-C ) , non-high-density-lipoprotein cholesterol ( non-HDL-C ) , high-sensitivity C-reactive protein ( hs-CRP ) , and cholesterol synthesis /absorption-related markers , were measured . Compared with those at the baseline , the levels of LDL-C , non-HDL-C , campesterol , and sitosterol were significantly reduced after 12 weeks of ezetimibe treatment in both groups . After adjusting for confounding factors , such as age , gender , smoking , and BMI , the levels of LDL-C and non-HDL-C displayed significantly greater reductions in the patients with T2DM ( -25.1 ± 13.6 % in LDL-C , -20.5 ± 11.2 % in non-HDL-C ) than those without T2DM ( -20.5 ± 7.8 % in LDL-C , P < 0.05 ; -17.4 ± 7.6 % in non-HDL-C , P < 0.05 ) . The reduction of the level of cholestanol was significantly and positively correlated with those of LDL-C and non-HDL-C in the patients with T2DM . Taken together , these findings indicate that ezetimibe could reduce the levels of atherogenic lipoproteins to a greater extent in hypercholesterolemic patients with T2DM than in those without T2DM BACKGROUND Despite the efficacy of statins in lowering low-density lipoprotein cholesterol ( LDL-C ) levels , many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction . The cholesterol absorption inhibitor , ezetimibe , has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins . This study was performed to compare the efficacy and safety of ezetimibe ( 10 mg ) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease ( CHD ) and are not at their LDL-C goal on the starting dose of atorvastatin . METHODS This was a 14-week , multicenter , r and omized , double-blind , active-controlled study conducted in 113 clinical research centers in 21 countries . Participants were adults with heterozygous familial hypercholesterolemia ( HeFH ) , CHD , or multiple ( > or = 2 ) cardiovascular risk factors , and a LDL-C level > or = 130 mg/dL after a 6- to 10-week dietary stabilization and atorvastatin ( 10 mg/day ) open-label run-in period . Eligible subjects continued to receive atorvastatin ( 10 mg ) and were r and omized to receive blinded treatment with ezetimibe ( 10 mg/day ; n = 305 ) or an additional 10 mg/day of atorvastatin ( n = 316 ) . The atorvastatin dose in both groups was doubled after 4 weeks , 9 weeks , or both when the LDL-C level was not at its goal ( < or = 100 mg/dL ) , so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day . The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14 . A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy . RESULTS The proportion of subjects reaching their target LDL-C level goal of < or = 100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group ( 22 % vs 7 % ; P < .01 ) . At 4 weeks , levels of LDL-C , triglycerides , and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin ( LDL-C -22.8 % versus -8.6 % ; P < .01 ) . The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone . CONCLUSIONS The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone 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 We compared the effects of lipid lowering with rosuvastatin ( RSV ) monotherapy versus intensified treatment by combining RSV with ezetimibe ( EZT ) on kidney function in patients undergoing vascular surgery . Patients were r and omly assigned to either 10 mg/d RSV ( n = 136 ) or RSV 10 mg/d plus EZT 10 mg/d ( RSV/EZT , n = 126 ) . At 12 months , a similar decrease in estimated glomerular filtration rate ( eGFR ) was noted . Patients who achieved a low-density lipoprotein cholesterol ( LDL-C ) of < 100 mg/dL had less eGFR decrease than those patients having an LDL-C limit of more than 100 mg/dL. There were no significant changes in the urinary total protein to creatinine ratio in either group . Significant microalbuminuria was evident in both the groups . Patients undergoing vascular surgery show deterioration in their renal function during the first year , despite statin therapy . Intensified lipid-lowering therapy by adding EZT does not appear to have any renoprotective effect BACKGROUND High-density lipoprotein ( HDL ) includes discrete subfractions . HDL exhibits anti-atherogenic properties , which have been partly linked to the activity of HDL-associated enzymes , such as the lipoprotein associated phospholipase A(2 ) ( HDL-LpPLA(2 ) ) and paraoxonase-1 ( PON1 ) . OBJECTIVE We assessed in an open-label r and omised study the effect of orlistat and ezetimibe , alone or in combination , on plasma HDL subclasses and HDL-associated enzyme activities in overweight and obese subjects ( body mass index > 28 kg/m(2 ) ) with hypercholesterolemia [ total cholesterol > 200 mg/100 ml ( 5.2 mmol/l ) ] . METHODS Eighty-six people were prescribed a low-fat low-calorie diet and were r and omly allocated to receive orlistat 120 mg , three times daily ( O group ) , ezetimibe 10 mg/day ( E group ) or both ( OE group ) for 6 months . HDL subfractions were determined using a polyacrylamide gel-tube electrophoresis method . RESULTS Levels of HDL cholesterol ( HDL-C ) and apolipoprotein AI did not change significantly in any group . In group O the cholesterol concentration of HDL-2 subclass increased significantly , while the cholesterol of HDL-3 subclass decreased significantly . In groups E and OE HDL-2 subclass did not significantly change , while the cholesterol concentration of HDL-3 subclass decreased significantly . We observed a non-significant decrease in the HDL-LpPLA(2 ) and PON1 activity in all groups . However , the ratios of both enzyme activities to low-density lipoprotein cholesterol ( LDL-C ) levels ( an index of atherogenicity ) significantly increased in all groups . CONCLUSION Although HDL-C levels did not change after treatment with orlistat and ezetimibe , alone or in combination , there were alterations of the HDL-2 and HDL-3 subclasses . The activity of HDL-LpPLA(2 ) and PON1 per mg LDL-C increased significantly in all groups BACKGROUND Inhibition of proprotein convertase subtilisin/kexin type 9 serine protease ( PCSK9 ) result ed in large reductions of low-density lipoprotein cholesterol ( LDL-C ) in phase 1 trials . We assessed the efficacy and safety of various doses and dosing intervals of REGN727 , a monoclonal antibody to PCSK9 , added to statins , to further lower LDL-C in patients with heterozygous familial hypercholesterolaemia . METHODS This multicentre , r and omised , placebo-controlled phase 2 trial was done at 16 lipid clinics in the USA and Canada . Between Jan 18 , 2011 , and Nov 7 , 2011 , we enrolled adults with heterozygous familial hypercholesterolaemia and LDL-C concentrations of 2·6 mmol/L or higher on stable diet and statin dose , with or without ezetimibe . Patients were r and omly assigned to receive REGN727 150 mg , 200 mg , or 300 mg every 4 weeks , or 150 mg every 2 weeks , or placebo every 2 weeks ( ratio 1:1:1:1:1 ) . R and omisation was stratified by concomitant use of ezetimibe at baseline . Investigators , study staff , and patients were masked to treatment group . Blinding was maintained by administration of placebo alternating with REGN727 for the groups of 4 week dosing . The primary endpoint was mean percent reduction in LDL-C from baseline at week 12 and was analysed in the modified intention-to-treat population with an analysis of covariance ( ANCOVA ) model with treatment group . This trial is registered in Clinical Trials.gov , number NCT 01266876 . FINDINGS 77 patients were r and omly assigned to study groups ( 15 - 16 patients per group ) and all were analysed . Least-squares ( LS ) mean LDL-C reduction from baseline to week 12 was 28·9 % ( SE 5·08 ) for 150 mg every 4 weeks ( p=0·0113 ) , 31·54 % ( 4·91 ) for 200 mg every 4 weeks ( p=0·0035 ) , 42·53 % ( 5·09 ) for 300 mg every 4 weeks ( p<0·0001 ) , and 67·90 % ( 4·85 ) for 150 mg every 2 weeks ( p<0·0001 ) , compared with 10·65 % ( 5·04 ) with  placebo . One serious adverse event was reported with placebo and none with REGN727 . No increases of more than three times the upper limit of normal were reported for hepatic transaminases or creatinine kinase . The most common adverse event was injection-site reaction with one patient in the group of 300 mg REGN727 terminating treatment . INTERPRETATION REGN727 was well tolerated and achieved substantial further LDL-C reduction in patients with heterozygous familial hypercholesterolaemia and elevated LDL-C treated with high-dose  statins , with or without ezetimibe . REGN727 has the potential to provide optimum control of LDL-C in patients with this disorder . FUNDING Sanofi US and Regeneron Pharmaceuticals Incorporated OBJECTIVES This study evaluated the safety and lipid-altering efficacy of ezetimibe/simvastatin ( E/S ) coadministered with extended-release niacin ( N ) in patients with type IIa or IIb hyperlipidemia . BACKGROUND Current guidelines recommend consideration of combination drug therapy to achieve optimal low-density lipoprotein cholesterol ( LDL-C ) lowering and broader lipid-altering effects when treating hypercholesterolemic patients at high risk for atherosclerotic cardiovascular events . METHODS In this 24-week multicenter , r and omized , double-blind study , 1,220 type IIa or IIb hyperlipidemic patients were r and omized to treatment with E/S ( 10/20 mg/day ) + N ( titrated to 2 g/day ) , or N ( titrated to 2 g/day ) , or E/S ( 10/20 mg/day ) . Changes from baseline in LDL-C ( primary ) and other secondary variables were assessed in the completers and modified intent-to-treat population s. RESULTS Coadministered E/S with N result ed in significantly greater reductions in LDL-C , non-high-density lipoprotein cholesterol , triglycerides , apolipoprotein B , and lipid/lipoprotein ratios , compared with either agent alone ( p < 0.001 ) . The combination increased levels of apolipoprotein A-I and high-density lipoprotein cholesterol significantly more than E/S ( p < 0.001 ) , and reduced high-sensitivity C-reactive protein levels significantly more than N ( p = 0.005 ) . A significantly greater percentage of patients discontinued the study in the N ( 25.0 % ) and N + E/S ( 23.3 % ) groups , compared with E/S ( 9.6 % , p < 0.001 ) because of clinical adverse experiences ( primarily flushing ) . Incidences of other clinical and laboratory adverse experiences ( liver- , muscle- , and gastrointestinal-related ) were similar for all groups . CONCLUSIONS Combination treatment with E/S plus N showed superior lipid-altering efficacy compared with N or E/S in type IIa or IIb hyperlipidemia patients and was generally well tolerated aside from N-associated flushing . This combination offers an effective , broad , lipid-altering therapy with improvements in lipid effects beyond LDL-C in these patients . ( To Evaluate Ezetimibe/Simvastatin and Niacin [ Extended Release Tablet ] in Patients With High Cholesterol We tested the security and efficacy of ezetimibe in the treatment of HIV-associated dyslipemia . Twenty HIV-infected patients were r and omly assigned to receive ezetimibe 10 mg/day or fluvastatin 80 mg/day . Patients receiving ezetimibe experienced a statistically significant ( P = 0.003 ) 20 % reduction in the concentration of LDL-cholesterol , similar to that observed with fluvastatin ( 24 % , P between groups 0.70 ) . We concluded that ezetimibe monotherapy effectively decreases LDL-cholesterol in HIV-infected patients BACKGROUND The aim of this study was to compare the effect on endothelial function of increasing statin dose to add-on ezetimibe in patients with coronary artery disease ( CAD ) already treated with statin . METHODS AND RESULTS Two-hundred and forty-three patients with CAD and low-density lipoprotein cholesterol ( LDL-C ) ≥70 mg/dl even after treatment with atorvastatin ( 10 mg ) were prospect ively r and omized to the ezetimibe addition ( 10 mg ) group ( A10E10 ; n=117 ) or to the double atorvastatin dose ( to 20 mg ; A20 ; n=133 ) group for 12 weeks . Primary endpoint was change in endothelial function measured by logarithmic-scale reactive hyperemia index ( L_RHI ) . After treatment , high-sensitivity C-reactive protein ( hs-CRP ) and all lipids except triglyceride and high-density lipoprotein cholesterol were significantly reduced in both groups . The mean percent changes in LDL-C for the A10E10 and A20 groups were -25.8 % and -9.1 % , respectively ( P<0.001 ) . L_RHI increased from 0.47 to 0.62 in the A20 group ( P<0.001 ) , but not in the A10E10 group ( from 0.45 to 0.48 , P=0.399 ) . Absolute change in L_RHI was significantly higher in the A20 than A10E10 group ( 0.02±0.29 vs. 0.16±0.27 , P<0.001 ) . CONCLUSIONS Statin and ezetimibe have different effects on endothelial function independent from LDL-C-lowering effects
Conclusions Ezetimibe monotherapy ( 10 mg/day ) showed a small ( 7.06 % ) but statistically significant reduction in the plasma levels of Lp(a ) in patients with primary hypercholesterolemia .
According to current literature , this magnitude of reduction seems to have no clinical relevance .
Background and Aims Ezetimibe reduces plasma low-density lipoprotein cholesterol ( LDL-C ) levels by up to 20 % .
However , its effect on plasma lipoprotein(a ) [ Lp(a ) ] concentrations in patients with primary hypercholesterolemia has not been defined .
Objective Therefore , we performed a systematic review and meta- analysis to assess this effect based on the available r and omized controlled trials ( RCTs ) .