Comparison of the effect of simvastatin versus simvastatin/ezetimibe versus rosuvastatin on markers of inflammation and oxidative stress in subjects with hypercholesterolemia. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial. Effects of gemfibrozil or simvastatin on apolipoprotein-B-containing lipoproteins, apolipoprotein-CIII and lipoprotein(a) in familial combined hyperlipidaemia. Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2 Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Effects of ezetimibe on remnant-like particle cholesterol, lipoprotein (a), and oxidized low-density lipoprotein in patients with dyslipidemia. Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis 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. Comparison of Effects of Morning Versus Evening Administration of Ezetimibe/Simvastatin on Serum Cholesterol in Patients with Primary Hypercholesterolemia Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome. Effects of ezetimibe on plasma lipoproteins in severely hypercholesterolemic patients treated with regular LDL-apheresis and statins. The effect of dietary fat content on plasma noncholesterol sterol concentrations in patients with familial hypercholesterolemia treated with simvastatin. The effect of ezetimibe and simvastatin on hemostasis in patients with isolated hypercholesterolemia. Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program). Effect of gemfibrozil on lipoprotein abnormalities in chronic renal insufficiency: a controlled study in human chronic renal disease. Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-density lipoprotein subclass distribution and lipoprotein(a). Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with non-insulin-dependent diabetes mellitus and hyperlipoproteinemia.
OBJECTIVES Statins may exhibit anti-inflammatory and antioxidant effects . Whether different statins at equivalent doses or the combination of low-dose statin with ezetimibe have comparable anti-inflammatory and antioxidant effects is unknown . The aim of this study was to compare the effects of simvastatin , simvastatin/ezetimibe or rosuvastatin at equivalent low-density lipoprotein cholesterol lowering doses on inflammation and oxidative stress indices in subjects with hypercholesterolemia . METHODS This was a pre-specified analysis of a prospect i ve , r and omized , open-label , blinded endpoint ( PROBE ) study . We enrolled one hundred and fifty three ( n = 153 ) hypercholesterolemic subjects who were r and omized to receive simvastatin 40 mg or simvastatin/ezetimibe 10/10 mg or rosuvastatin 10 mg daily .  Plasma 8-Epi prostagl and in F2 alpha ( 8-epiPGF2a ) , oxidized LDL ( oxLDL ) and lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) activity and mass were measured at baseline and following 12 weeks of treatment . RESULTS A significant reduction in plasma 8-isoprostane and oxLDL levels was observed in all treatment groups [ by 10 % , 8 % and 6 % ( p < 0.05 compared with baseline ) and 41 % , 40 % and 39 % ( p < 0.001 compared with baseline ) in simvastatin , simvastatin/ezetimibe and rosuvastatin groups , respectively ] . In all treatment groups a significant reduction in total plasma Lp-PLA2 activity and mass was observed ( by 36 % , 31 % and 38 % and 36 % , 32 % and 32 % for simvastatin , simvastatin/ezetimibe and rosuvastatin , respectively , p < 0.001 compared with baseline ) . No intergroup differences were observed . CONCLUSIONS Simvastatin 40 mg , simvastatin/ezetimibe 10/10 mg and rosuvastatin 10 mg significantly reduced 8-epiPGF2a , oxLDL and Lp-PLA2 activity and mass to a similar extent 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 BACKGROUND Niacin and lovastatin are both effective drugs for the treatment of hypercholesterolemia and are among the drugs of first choice recommended by the adult treatment panel . To date , however , no studies have directly compared the lipoprotein-modifying effects and safety of lovastatin and niacin across their usual dosage range in patients with primary hypercholesterolemia . METHODS The efficacy and safety of lovastatin and niacin were compared in a controlled , r and omized , open-label study of 26 weeks ' duration that was conducted at five lipid clinics . One hundred thirty-six patients with primary hypercholesterolemia participated in the study . Entry criteria were a low-density lipoprotein ( LDL ) cholesterol level greater than 4.37 mmol/L ( 160 mg/dL ) with coronary heart disease and /or more than two coronary heart disease risk factors or an LDL cholesterol level greater than 5.19 mmol/L ( 190 mg/dL ) in patients without coronary heart disease or less than two coronary heart disease risk factors . The study consisted of a 4-week diet run-in period after which eligible patients were r and omly assigned to receive treatment with either lovastatin ( 20 mg/d ) or niacin ( 1.5 g/d ) for 10 weeks . On the basis of the LDL cholesterol response and patient tolerance , the doses were sequentially increased to 40 and 80 mg/d of lovastatin or 3 and 4.5 g/d of niacin after 10 and 18 weeks of treatment , respectively . RESULTS In the two patient groups , 66 % of patients treated with lovastatin and 54 % of patients treated with niacin underwent full dosage titration . At all time points , lovastatin was significantly ( P < .01 ) more effective than niacin in reducing LDL cholesterol levels ( 26 % vs 5 % at week 10 , 28 % vs 16 % at week 18 , and 32 % vs 23 % at week 26 ) , whereas niacin was more effective ( P < .01 ) in increasing high-density lipoprotein cholesterol levels ( 6 % vs 20 % at week 10 , 8 % vs 29 % at week 18 , and 7 % vs 33 % at week 26 ) . Niacin reduced Lp(a ) lipoprotein levels by 35 % at week 26 , whereas lovastatin had no effect . Cutaneous flushing was the most common side effect during treatment with niacin . CONCLUSIONS Lovastatin and niacin both exerted favorable dose-dependent changes on the concentrations of plasma lipids and lipoproteins .  Lovastatin was more effective in reducing LDL cholesterol concentrations , whereas niacin was more effective in increasing high-density lipoprotein cholesterol concentrations and reducing the Lp(a ) lipoprotein level .  Lovastatin was better tolerated than niacin , in large part because of the common cutaneous side effects of niacin BACKGROUND Familial combined hyperlipidaemia ( FCH ) , characterized by elevated very-low-density lipoprotein ( VLDL ) and /or low-density lipoprotein ( LDL ) , is associated with an increased prevalence of premature cardiovascular disease . Therefore , lipid-lowering is frequently indicated . METHODS We evaluated in a parallel , double-blind r and omized fashion the effect of gemfibrozil ( 1200 mg/day ) ( n = 40 ) or simvastatin ( 20 mg/day ) ( n = 41 ) on lipids , apolipoprotein-B (apo-B)-containing lipoproteins , apo-CIII and lipoprotein(a ) [ Lp(a ) ] , in 81 well-defined FCH patients . RESULTS While both drugs lowered plasma cholesterol and triglyceride levels , gemfibrozil lowered plasma triglycerides more effectively by reduction of triglycerides in VLDL and LDL , whereas simvastatin was more effective in its reduction of total plasma cholesterol by exclusively decreasing LDL cholesterol . High-density lipoprotein ( HDL ) increased to an equal extent on both therapies . Total serum apo-B levels were reduced with both drugs ; however , gemfibrozil decreased apo-B only in VLDL + IDL , whereas simvastatin decreased apo-B in both VLDL + IDL and LDL . In keeping with a more effective reduction of VLDL particles , a more pronounced reduction of apo-CIII also was observed after gemfibrozil , which correlated with the reduction in plasma triglycerides . Baseline concentrations of Lp(a ) showed a wide range in both treatment groups . Median Lp(a ) levels increased after simvastatin , but were not affected by gemfibrozil . CONCLUSION Both therapies exhibited their specific effects , although none of the drugs alone completely normalized the lipid profiles of these patients with FCH . Therefore , the choice of treatment should be based on the most elevated lipoprotein fraction , and in some cases a combination of the two drugs may be indicated Objective — Lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) is a predictor for incident atherosclerotic disease . We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA2 activity and mass . Methods and Results — In 50 patients with Type IIA dyslipidemia were administered rosuvastatin ( 10 mg daily ) , whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy ( 10 mg daily ) . Fifty patients with Type IV dyslipidemia were given micronised fenofibrate ( 200 mg daily ) . Low- and high-density lipoprotein ( LDL and HDL , respectively ) subclass analysis was performed electrophoretically , whereas lipoprotein subfractions were isolated by ultracentrifugation . Ezetimibe reduced plasma Lp-PLA2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions . Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA2 on dense LDL subfraction ( LDL-5 ) . Fenofibrate preferentially reduced the Lp-PLA2 activity and mass associated with the VLDL+IDL and LDL-5 subfractions . Among studied drugs only fenofibrate increased HDL-associated Lp-PLA2 ( HDL-Lp-PLA2 ) activity and mass attributable to a preferential increase in Lp-PLA2 associated with the HDL-3c subfraction . Conclusion — Ezetimibe , rosuvastatin , and fenofibrate reduce Lp-PLA2 activity and mass associated with the atherogenic apoB-lipoproteins . Furthermore , fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA2 . The clinical implication s of these effects remain to be established OBJECTIVE To compare the efficacy and safety of 10 mg of ezetimibe coadministered with simvastatin with the safety and efficacy of simvastatin monotherapy for patients with hypercholesterolemia . PATIENTS AND METHODS This multicenter double-blind , placebo-controlled , factorial study enrolled 887 patients with hypercholesterolemia ( low-density lipoprotein cholesterol [ LDL-C ] , 145 - 250 mg/dL ; triglycerides , < or = 350 mg/dL ) . Patients were r and omized to 1 of 10 treatments -- placebo , ezetimibe at 10 mg/d , simvastatin at 10 , 20 , 40 , or 80 mg/d , or simvastatin at 10 , 20 , 40 , or 80 mg/d plus ezetimibe at 10 mg/d for 12 weeks . The study began March 13 , 2001 , and ended January 8 , 2002 . The primary efficacy end point was the mean percent change in LDL-C levels from baseline to study end point ( last available postbaseline LDL-C measurement ) for the pooled ezetimibe/simvastatin group vs the pooled simvastatin monotherapy group . RESULTS Coadministration of ezetimibe/simvastatin was significantly ( P<.001 ) more effective than simvastatin alone in reducing LDL-C levels for the pooled ezetimibe/simvastatin vs pooled simvastatin analysis and at each specific dose comparison . The decrease in LDL-C levels with coadministration of ezetimibe and the lowest dose of simvastatin , 10 mg , was similar to the decrease with the maximum dose of simvastatin , 80 mg . A significantly ( P<.001 ) greater proportion of patients in the ezetimibe/simvastatin group achieved target LDL-C levels compared with those in the monotherapy group . Treatment with ezetimibe/simvastatin also led to greater reductions in total cholesterol , triglyceride , non-high-density lipoprotein cholesterol , and apolipoprotein B levels compared with simvastatin alone ; both treatments increased high-density lipoprotein cholesterol levels similarly . The safety and tolerability profiles for the ezetimibe/simvastatin and monotherapy groups were similar . CONCLUSION Through dual inhibition of cholesterol absorption and synthesis , coadministration of ezetimibe/simvastatin offers a highly efficacious and well-tolerated lipid-lowering strategy for treating patients with primary hypercholesterolemia 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 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 Importance Human genetic studies have indicated that plasma lipoprotein(a ) ( Lp[a ] ) is causally associated with the risk of coronary heart disease ( CHD ) , but r and omized trials of several therapies that reduce Lp(a ) levels by 25 % to 35 % have not provided any evidence that lowering Lp(a ) level reduces CHD risk . Objective To estimate the magnitude of the change in plasma Lp(a ) levels needed to have the same evidence of an association with CHD risk as a 38.67-mg/dL ( ie , 1-mmol/L ) change in low-density lipoprotein cholesterol ( LDL-C ) level , a change that has been shown to produce a clinical ly meaningful reduction in the risk of CHD . Design , Setting , and Participants A mendelian r and omization analysis was conducted using  individual participant data  from 5 studies and with external validation using summarized data from 48 studies . Population -based prospect i ve cohort and case-control studies featured 20 793 individuals with CHD and 27 540 controls with individual participant data , whereas summarized data included 62 240 patients with CHD and 127 299 controls . Data were analyzed from November 2016 to March 2018 . Exposures Genetic LPA score and plasma Lp(a ) mass concentration . Main Outcomes and Measures Coronary heart disease .  Results Of the included study participants , 53 % were men , all were of white European ancestry , and the mean age was 57.5 years . The association of genetically predicted Lp(a ) with CHD risk was linearly proportional to the absolute change in Lp(a ) concentration . A 10-mg/dL lower genetically predicted Lp(a ) concentration was associated with a 5.8 % lower CHD risk ( odds ratio [ OR ] , 0.942 ; 95 % CI , 0.933 - 0.951 ; P = 3 × 10−37 ) , whereas a 10-mg/dL lower genetically predicted LDL-C level estimated using an LDL-C genetic score was associated with a 14.5 % lower CHD risk ( OR , 0.855 ; 95 % CI , 0.818 - 0.893 ; P = 2 × 10−12 ) . Thus , a 101.5-mg/dL change ( 95 % CI , 71.0 - 137.0 ) in Lp(a ) concentration had the same association with CHD risk as a 38.67-mg/dL change in LDL-C level . The association of genetically predicted Lp(a ) concentration with CHD risk appeared to be independent of changes in LDL-C level owing to genetic variants that mimic the relationship of statins , PCSK9 inhibitors , and ezetimibe with CHD risk . Conclusions and Relevance The clinical benefit of lowering Lp(a ) is likely to be proportional to the absolute reduction in Lp(a ) concentration . Large absolute reductions in Lp(a ) of approximately 100 mg/dL may be required to produce a clinical ly meaningful reduction in the risk of CHD similar in magnitude to what can be achieved by lowering LDL-C level by 38.67 mg/dL ( ie , 1 mmol/L ) 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 : Ezetimibe , a first-in-its-class inhibitor of cholesterol absorption , is an effective agent for combined use with statins to achieve low-density lipoprotein cholesterol ( LDL-C ) goals . Ezetimibe in combination with simvastatin as a single-tablet formulation has proven to be highly effective in reducing serum LDL-C through the dual inhibition of cholesterol absorption and bio synthesis . The effect of time of administration on efficacy of this combination therapy has not been evaluated . Objective : To compare the effects of morning versus evening administration of ezetimibe/simvastatin on serum cholesterol levels of patients with primary hypercholesterolemia . Methods : In this multicenter , open-label , r and omized , 2-sequence , 2-period crossover study , patients with primary hypercholesterolemia r and omly received ezetimibe/simvastatin 10 mg/20 mg once daily , either in the morning ( within 1 hour of breakfast ) or in the evening ( within 1 hour of dinner ) for 6 weeks . Results : Data on 171 patients ( 87 in the morning administration group and 84 in the evening administration group ) were analyzed . A significant reduction ( p ≤ 0.001 ) in the total cholesterol , triglyceride , high-density lipoprotein cholesterol , LDL-C , apo-lipoprotein B , and high-sensitivity C-reactive protein ( hs-CRP ) from baseline was achieved after each treatment . Noninferiority of morning administration versus evening administration was shown in the percentage reduction of the LDL-C level from baseline ( difference , –1.62 % ; 90 % CI –4.94 to 1.70 ) . No significant difference was found between groups with respect to the percentage of changes in other lipid parameters from baseline . Furthermore , there was no significant difference in the percentage of change in hs-CRP as an antiinflammatory marker between the morning and evening administration groups . The frequency of adverse events was similar between groups . Conclusions : Morning administration of ezetimibe/simvastatin 10 mg/20 mg is noninferior to evening administration with respect to LDL-C – lowering ability This multicenter , r and omized , double-blind , placebo-controlled clinical study assessed the efficacy and safety of ezetimibe administered with lovastatin in primary hypercholesterolemia .  After dietary stabilization , a 2- to 12-week washout period , and a 4-week single-blind placebo lead-in period , 548 patients with low-density lipoprotein ( LDL ) cholesterol > or = 145 mg/dl ( 3.75 mmol/L ) and < or = 250 mg/dl ( 6.47 mmol/L ) and triglycerides < or = 350 mg/dl ( 3.99 mmol/L ) were r and omized to one of the following , administered daily for 12 weeks :  ezetimibe 10 mg ; lovastatin 10 , 20 , or 40 mg ; ezetimibe 10 mg plus lovastatin 10 , 20 , or 40 mg ; or placebo . The primary efficacy variable was percentage decrease in direct LDL cholesterol from baseline to end point for pooled ezetimibe plus lovastatin versus pooled lovastatin alone . Ezetimibe plus lovastatin significantly improved concentrations of LDL cholesterol , high-density lipoprotein ( HDL ) cholesterol , and triglycerides compared with lovastatin alone ( p < 0.01 ) . The coadministration of ezetimibe provided an incremental 14 % LDL cholesterol decrease , a 5 % HDL cholesterol increase , and a 10 % decrease in triglycerides compared with pooled lovastatin alone . Ezetimibe plus lovastatin provided mean LDL cholesterol decreases of 33 % to 45 % , median triglyceride decreases of 19 % to 27 % , and mean HDL cholesterol increases of 8 % to 9 % , depending on the statin dose . The coadministration of ezetimibe 10 mg plus the starting dose of lovastatin ( 10 mg ) provided comparable efficacy to high-dose lovastatin ( 40 mg ) across the lipid profile ( LDL cholesterol , HDL cholesterol , and triglycerides ) .  Ezetimibe plus lovastatin was well tolerated , with a safety profile similar to both lovastatin alone and placebo . The coadministration of ezetimibe and lovastatin may offer a new treatment option in lipid management of patients with hypercholesterolemia OBJECTIVE Dyslipidaemia is very common in patients with polycystic ovary syndrome ( PCOS ) but , beyond plasma lipids , atherogenic lipoprotein ( Lp ) and apolipoprotein ( apo ) alterations are still ill defined . DESIGN We measured concentrations of apoB , Lp(a ) and small , dense low-density lipoprotein ( LDL )  in 42 patients with PCOS [ age : 28 + /- 7 years , body mass index ( BMI ): 27 + /- 5 kg/m(2 ) ] vs. 37 age- and BMI -matched healthy controls . METHODS Elevated  Lp(a ) levels  considered were those > 30 mg/dl while elevated apoB concentrations were those > 100 g/l . RESULTS Polycystic ovary syndrome showed increased triglycerides levels ( p = 0.0011 ) and lower high-density lipoprotein (HDL)-cholesterol concentrations ( p = 0.0131 ) while total- and LDL cholesterol were similar . PCOS also showed smaller LDL size ( p = 0.0005 ) , higher levels of total small , dense LDL ( p < 0.0001 ) , higher concentrations of Lp(a ) , as considered as absolute values ( p = 0.0143 ) and log-transformed ( p = 0.0014 ) , while no differences were found in apoB levels . Elevated Lp(a ) concentrations were found in 24 % of PCOS , while elevated apoB levels were relatively uncommon ( 14 % ) . Spearman correlation analysis revealed that Lp(a ) concentrations were weakly correlated only with HDL-cholesterol levels ( r = -0.378 , p = 0.0431 ) . In addition , 36 % of patients with PCOS with normal plasma lipid profile showed elevated levels of Lp(a ) , apoB or small , dense LDL . CONCLUSIONS Atherogenic Lp abnormalities may be found in one-third of women with PCOS who have a normal lipid pattern . Future prospect i ve studies are needed to test to which extent such atherogenic forms of dyslipidaemia may contribute to the increased cardiovascular risk in young women with PCOS 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 The effects of a low-fat , low-cholesterol diet ( LFD ) or a higher-fat , higher-cholesterol diet ( HFD ) on plasma concentrations of lipids , lipoproteins , lathosterol ( an index of cholesterol synthesis rate ) , and plant sterols were determined in 19 patients with familial hypercholesterolemia ( FH ) treated with simvastatin .  The study followed a r and omized crossover design including two 8-week diet periods . The LFD significantly decreased plasma lathosterol ( -22 % ) , cholesterol ( -6 % ) , low-density lipoprotein ( LDL ) cholesterol ( -6 % ) , and high-density lipoprotein ( HDL ) cholesterol ( -7 % ) levels compared with the HFD . Decreases in plasma lathosterol and LDL cholesterol concentrations in patients during the LFD were significantly correlated ( r = .522 , n = 19 , P < .05 ) . These results suggest that a LFD may enhance the decrease in cholesterol synthesis induced by simvastatin treatment , and in this way might contribute to the decrease in plasma cholesterol levels when the fat content of the diet is reduced in simvastatin-treated FH patients The aim of this study was to assess the strength of hemostatic effects of ezetimibe , administered alone or in combination with simvastatin , in patients with isolated hypercholesterolemia . One hundred and four patients with isolated primary hypercholesterolemia were r and omized to one of four treatment groups , simultaneously treated for 90 days with ezetimibe ( 10 mg daily ) , simvastatin ( 40 mg daily ) , ezetimibe ( 10 mg daily ) plus simvastatin ( 40 mg daily ) , or placebo .  Plasma lipids/lipoproteins and hemostatic cardiovascular risk factors were assessed on the day of r and omization and after 30 and 90 days of therapy . Despite improving lipid/lipoprotein profile by both simvastatin and ezetimibe , only simvastatin reduced plasma levels/activity of fibrinogen , factor VII , factor X , von Willebr and factor , and plasminogen activator inhibitor-1 . The strongest effects on plasma lipids/lipoproteins and the assessed hemostatic variables were observed when patients were treated with both simvastatin and ezetimibe . With the exception of oxidized low-density lipoproteins , the hemostatic effects of simvastatin or simvastatin plus ezetimibe did not correlate with the changes in plasma lipids/lipoproteins . Our study shows that simvastatin is a more effective agent than ezetimibe in affecting coagulation and fibrinolysis in individuals with isolated hypercholesterolemia . It also suggests that the combined administration of simvastatin and ezetimibe may bring more benefits to patients than monotherapy with only one of these agents Elevated lipoprotein(a ) [ Lp(a ) ] is independently associated with increased cardiovascular risk . However , treatment options for elevated Lp(a ) are limited . Alirocumab , a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 , reduced low-density lipoprotein cholesterol ( LDL-C ) by up to 62 % from baseline in phase 3 studies , with adverse event rates similar between alirocumab and controls . We evaluated the effect of alirocumab on serum Lp(a ) using pooled data from the phase 3 ODYSSEY program : 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included . Eight studies evaluated alirocumab 75 mg every 2 weeks ( Q2W ) , with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 ( 75/150 mg Q2W ) ; the other 2 studies evaluated alirocumab 150-mg Q2W from the outset . Comparators were placebo or ezetimibe . Eight studies were conducted on a background of statins , and 2 studies were carried out with no statins . Alirocumab was associated with significant reductions in Lp(a ) , regardless of starting dose and use of concomitant statins . At week 24 , reductions from baseline were 23 % to 27 % with alirocumab 75/150-mg Q2W and 29 % with alirocumab 150-mg Q2W ( all comparisons p < 0.0001 vs controls ) . Reductions were sustained over 78 to 104 weeks . Lp(a ) reductions with alirocumab were independent of race , gender , presence of familial hypercholesterolemia , baseline Lp(a ) , and LDL-C concentrations , or use of statins . In conclusion , in addition to marked reduction in LDL-C , alirocumab leads to a significant and sustained lowering of Lp(a ) BACKGROUND Renal dyslipoproteinemia is characterized by the accumulation of intact and partially metabolized triglyceride-rich lipoproteins . Reduced lipolytic enzyme activities may be one of the major pathophysiological mechanisms contributing to a retarded catabolism of these lipoproteins in patients with renal insufficiency . OBJECTIVE To evaluate the effect of gemfibrozil treatment on renal dyslipoproteinemia . STUDY DESIGN A r and omized , controlled open study with 2 parallel groups . OUTCOME VARIABLES Plasma concentrations of lipids , apolipoproteins and lipoprotein particles . PATIENTS AND METHODS Fifty-seven non-nephrotic , non-diabetic patients with moderately advanced renal insufficiency were r and omized to either treatment with gemfibrozil at dosages from 300 to 900 mg/day ( n = 28 ) or dietary counseling ( n = 29 ) . The intervention period was 12 months . Plasma concentrations of lipids , apolipoproteins and apoA- and apoB-containing lipoprotein particles were determined at the entry and after 6 and 12 months of treatment . RESULTS No serious adverse effects occurred during the study . Six patients experienced mild gastrointestinal symptoms and prematurely withdrew from the drug treatment . In the group treated with gemfibrozil the plasma concentrations of triglycerides , total cholesterol , very low density lipoprotein ( VLDL ) and low density ( LDL ) cholesterol decreased significantly by 47 , 13 , 43 and 14 % , respectively , in comparison to baseline . High density lipoprotein ( HDL ) cholesterol increased significantly by 18 % . ApoB , apoC-III , apoC-III in heparin-manganese precipitate ( reflecting apoC-III in VLDL and LDL ) and apoE decreased significantly by 21 , 18 , 26 and 49 % , respectively . Furthermore , gemfibrozil treatment result ed in the reduction of plasma concentrations of complex ( LP-Bc ) and simple ( LP-B ) apoB-containing lipoprotein particles by 22 and 7 % , respectively . However , these changes were not statistically significant . There was a slight , insignificant increase in the levels of LP-A-I : A-II particles and no change in the levels of LP-A-I particles . In contrast to the effect of the pharmacological intervention , the dietary counseling only result ed in minor changes in the plasma lipid and apolipoprotein profiles . The only significant changes were a 10 % increase in HDL cholesterol and a 35 % decrease in apoE. CONCLUSIONS Gemfibrozil treatment significantly reduces both plasma lipids and apoB , apoC-III and apoE concentrations in patients with moderately advanced renal insufficiency . The results of this study indicate that gemfibrozil enhances the clearance of apoB-containing triglyceride-rich lipoproteins OBJECTIVES To test the hypothesis that a garlic supplement alters plasma lipoproteins , postpr and ial lipemia , low-density lipoprotein ( LDL ) size and high-density lipoprotein ( HDL ) subclass distribution differently in 50 moderately hypercholesterolemic subjects classified as LDL subclass pattern A or B. BACKGROUND Garlic has been variably reported to reduce or not affect plasma cholesterol values . Low-density lipoprotein pattern B is a common inherited disorder of lipoprotein metabolism that has been shown to have a significantly greater response to several lipid lowering treatments including low fat diet when compared with LDL pattern A individuals . METHODS A double blind , r and omized , placebo controlled trial in an outpatient lipid research clinic was performed and included fifty moderately hypercholesterolemic subjects ( mean LDL cholesterol = 166 + /- 22 mg/dl ) classified as LDL subclass pattern A ( predominantly large LDL , n = 22 ) or B ( predominantly small LDL , n = 28 ) . Following a two-month stabilization period , subjects were r and omly assigned to a placebo or 300 mg three times a day of a st and ardized garlic tablet for three months . RESULTS For all subjects , LDL pattern A and B subjects combined , garlic treatment for three months result ed in no significant change in total cholesterol , LDL cholesterol , HDL cholesterol , HDL subclass distribution , postpr and ial triglycerides , apolipoprotein B , lipoprotein ( a ) ( Lp[a ] ) , LDL peak particle diameter or LDL subclass distribution . There was no significant difference in response for the same parameters among subjects classified as LDL pattern A or B with the exception of significantly greater ( p = 0.01 ) reduction in mean peak particle diameter in pattern A subjects treated with either garlic or placebo . There was no significant change in LDL subclass distribution . CONCLUSIONS This investigation confirms that garlic therapy has no effect on major plasma lipoproteins and further , that it has no impact on HDL subclasses , Lp(a ) , apolipoprotein B , postpr and ial triglycerides or LDL subclass distribution .  Garlic may have a greater effect on LDL particle diameter in LDL pattern A compared with pattern B subjects . This difference was not reflected in other plasma lipid measurements 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 The aim of this study was to evaluate the efficacy and safety of ezetimibe 10 mg added to atorvastatin 20 mg compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease who did not reach low-density lipoprotein ( LDL ) cholesterol levels < 100 mg/dl with atorvastatin 20 mg . In this 6-week , multicenter , double-blind , r and omized , parallel-group study , 196 patients treated with atorvastatin 20 mg received atorvastatin 20 mg plus ezetimibe 10 mg or atorvastatin 40 mg for 6 weeks . Adding ezetimibe 10 mg to atorvastatin 20 mg produced significantly greater reductions in LDL cholesterol than increasing atorvastatin to 40 mg ( -31 % vs -11 % , p < 0.001 ) . Significantly greater reductions were also seen in non-high-density lipoprotein cholesterol , total cholesterol , and apolipoprotein B ( p < 0.001 ) . Significantly more patients reached LDL cholesterol levels < 100 mg/dl with atorvastatin 20 mg plus ezetimibe compared with atorvastatin 40 mg ( 84 % vs 49 % , p < 0.001 ) . The 2 treatment groups had comparable results for high-density lipoprotein cholesterol , triglycerides , apolipoprotein A-I , and high-sensitivity C-reactive protein . The incidences of clinical and laboratory adverse experiences were generally similar between groups . In conclusion , the addition of ezetimibe 10 mg to atorvastatin 20 mg was generally well tolerated and result ed in significantly greater lipid-lowering efficacy compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease Five multicenter , r and omized , double‐blind , placebo‐controlled studies were conducted in France to compare the efficacy and safety of once‐daily simvastatin treatment ( 10–40 mg/day ) with conventional therapy with gemfibrozil 900 mg/day , ciprofibrate 100 mg/day , bezafibrate 400 mg/day , and fenofibrate 300 or 400 mg/day in a total of 800 patients with hypercholesterolemia .  Simvastatin was associated with statistically significantly greater ( p ≪ 0.01 ) mean percent reductions in plasma low‐density lipoprotein ( LDL ) cholesterol compared with each of the five fibrate regimens , even when administered at its recommended starting dose of 10 mg/day . Furthermore , approximately 90 % of patients treated once daily with simvastatin experienced an at least 20 % decrease in plasma LDL cholesterol compared with only 36 to 68 % of patients treated with the individual fibrate agents ( p ≪ 0.05 ) . The effectiveness of simvastatin in reducing LDL cholesterol did not differ as a function of the baseline plasma concentrations of total cholesterol or triglycerides . In contrast , the effectiveness of fibrate therapy in lowering plasma LDL cholesterol levels was significantly diminished ( p ≪ 0.05 ) among patients with triglyceride concentrations  >  1.7 mmol/1 . Plasma highdensity lipoprotein ( HDL ) cholesterol levels were increased by approximately 10 % after treatment with simvastatin or the fibrates . Although fibrate therapy was more effective overall in lowering plasma triglyceride levels , the effectiveness of simvastatin in reducing plasma triglyceride levels was generally 2‐ to 4‐fold greater in patients with hypercholesterolemia associated with triglyceride levels ≫ 2.3 mmol/1 than in those with hypercholesterolemia associated with triglyceride levels < 2.3 mmol/1 . The results of these studies confirm the superiority of simvastatin to st and ard fibrate therapy in reducing plasma levels of total and LDL cholesterol . They further indicate that once‐daily treatment with simvastatin is effective in patients with isolated hypercholesterolemia or hypercholesterolemia associated with elevated triglyceride levels In a double-blind , r and omized crossover study , 29 patients with non-insulin-dependent diabetes mellitus ( NIDDM ) and hyperlipoproteinemia were treated with gemfibrozil ( 1,200 mg/d ) or simvastatin ( 10 mg/d ) for 4 months . After gemfibrozil treatment , the insulin concentration was increased during the major part of the intravenous glucose tolerance test ( IVGTT ) and during the hyperinsulinemic euglycemic clamp . Similar but less pronounced elevations were caused by simvastatin .  Insulin sensitivity decreased by 27 % and 28 % during gemfibrozil and simvastatin treatment , respectively . Low-density lipoprotein ( LDL ) cholesterol was decreased with simvastatin treatment by 24 % . The LDL cholesterol level was not changed by gemfibrozil , but very-low-density lipoprotein ( VLDL ) cholesterol was reduced by 40 % . The VLDL triglyceride concentration was reduced to a significantly greater extent by gemfibrozil . After gemfibrozil treatment , lipoprotein(a ) [ Lp(a ) ] was decreased by 24 % , and the plasma free fatty acid ( FFA ) concentration was increased by 20 % and skeletal muscle lipoprotein lipase activity ( LPLA ) by 37 % . Although simvastatin more effectively decreased LDL cholesterol levels and the LDL to high-density lipoprotein ( HDL ) ratio , it can not be cl aim ed unreservedly that this drug is necessarily preferable in NIDDM patients . Gemfibrozil improved triglyceride removal and decreased VLDL concentrations , with qualitative changes in LDL . The apparent effects on insulin sensitivity are difficult to evaluate and need further study
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 ) .