Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Rosuvastatin alone or with extended-release niacin: a new therapeutic option for patients with combined hyperlipidemia. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). Superior benefit of aggressive lipid-lowering therapy for high- risk patients using statins: the SUBARU study--more hypercholesterolemic patients achieve Japan Atherosclerosis Society LDL-C goals with rosuvastatin therapy than with atorvastatin therapy. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Long-term safety and efficacy of fenofibric acid in combination with statin therapy for the treatment of patients with mixed dyslipidemia. Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia. Effect of fixed‐dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS‐ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe) The effect of ezetimibe and simvastatin on hemostasis in patients with isolated hypercholesterolemia. Treating to target patients with primary hyperlipidaemia:comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study) Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe Efficacy and safety of extended-release niacin/laropiprant plus statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia. The influence of statin-fibrate combination therapy on lipids profile and apolipoprotein A5 in patients with acute coronary syndrome Randomized comparative study of the effects of treatment with once-daily, niacin extended-release/lovastatin and with simvastatin on lipid profile and fibrinolytic parameters in Taiwan.
OBJECTIVE Evaluate the lipid-altering effects of ezetimibe added to ongoing statin therapy , statin titration , switching from statin monotherapy to a more potent statin or to ezetimibe/simvastatin . METHODS A pooled analysis of patient-level data from 17 double-blind , active or placebo-controlled studies of 8667 hypercholesterolemic adults r and omized to  ezetimibe 10 mg added to ongoing statins , statin titration ( doubling ) , or switching from ongoing statins to rosuvastatin ( 10 mg ) or to ezetimibe/simvastatin ( 10/20 and 40 mg ) . Percent change from baseline in low-density lipoprotein cholesterol ( LDL-C ) was estimated by analysis of variance . Percent of patients who achieved LDL-C and other guideline -recommended targets , and target lipid levels by baseline distance to goal were evaluated . RESULTS LDL-C percent change from baseline was -26.0 for ezetimibe added to ongoing statin therapy , -27.6 for switching from ongoing statin to ezetimibe/simvastatin , -19.7 for switching to rosuvastatin 10 mg , and -9.7 for dose doubling of the ongoing statin . For patients within 0.8 mmol/L ( 30 mg/dL ) of the target at baseline , LDL-C target attainment rates were 75.9 % for adding ezetimibe to ongoing statin , 72.8 % for switching to ezetimibe/simvastatin , 61.8 % for switching to rosuvastatin , and 44.3 % for statin dose-doubling . Similarly , improvements in other lipids and achievement of non-high-density lipoprotein cholesterol and apolipoprotein B targets among this patient group were largest for ezetimibe added to ongoing statins and switching to ezetimibe/simvastatin ; switching to rosuvastatin 10 mg and statin dose-doubling were less effective . CONCLUSIONS Adding ezetimibe to ongoing statin therapy appeared to be an effective option for patients who do not achieve lipid-lowering goals on statins alone Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level < 80 mg/dL. As a result , add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration BACKGROUND Reduction in low-density lipoprotein cholesterol ( LDL-C ) improves clinical outcomes in patients with chronic coronary artery disease and acute coronary syndromes ( ACSs ) . The combination of ezetimibe/simvastatin produces greater reductions in LDL-C compared to simvastatin monotherapy . The IMProved Reduction of Outcomes : Vytorin Efficacy International Trial ( IMPROVE-IT ) is a multicenter , r and omized , double-blind , active-control trial design ed to test the hypothesis that the addition of ezetimibe to statin therapy , using ezetimibe/simvastatin , will translate into increased clinical benefit on cardiovascular outcomes relative to simvastatin monotherapy in patients with ACS . STUDY DESIGN The study will recruit up to 18,000 moderate- to high-risk patients stabilized after ACS . Patients are r and omized in a 1:1 ratio to once-daily doses of either ezetimibe/simvastatin 10/40 mg or simvastatin monotherapy 40 mg . Follow-up visits are at 1 and 4 months , and every 4 months thereafter . If consecutive measures of LDL-C are > 79 mg/dL at follow-up visits , the simvastatin dose will be increased to 80 mg in a double-blind manner . The primary end point is the first occurrence of cardiovascular death , nonfatal myocardial infa rct ion , rehospitalization for unstable angina , coronary revascularization ( occurring at least 30 days after r and omization ) , or stroke . Patients will be followed for a minimum of 2.5 years and until at least 5,250 patients experience a primary end point . SUMMARY IMPROVE-IT will determine whether the addition of ezetimibe to statin therapy , using ezetimibe/simvastatin , improves cardiovascular outcomes compared with simvastatin monotherapy in patients after ACS . In addition , the difference in achieved LDL-C levels between the groups will provide data on whether the target for LDL-C lowering should be reduced further Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein ( HDL ) cholesterol . The authors assessed the efficacy and safety of rosuvastatin monotherapy , extended-release ( ER ) niacin monotherapy , or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia . In a 24-week , open-label , multicenter trial , men and women aged > or = 18 years with fasting levels of total cholesterol > or = 200 mg/dL , HDL cholesterol > or = 45 mg/dL , triglycerides 200 - 800 mg/dL , and apolipoprotein B > or = 110 mg/dL were r and omly assigned to one of four treatment groups : rosuvastatin 10 - 40 mg , ER niacin 0.5 - 2 g , rosuvastatin 40 mg plus ER niacin 0.5 - 1 g , or rosuvastatin 10 mg plus ER niacin 0.5 - 2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein ( LDL ) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol . Triglyceride reductions were similar among the four treatment groups . ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy . Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin . In this study , rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol ( HDL-C ) and elevated triglycerides for patients at moderately high to high coronary heart disease ( CHD ) risk . Combination therapy is often required to achieve multiple lipid treatment goals , and > or = 50 % reduction in low-density lipoprotein cholesterol ( LDL-C ) is needed in some patients to achieve aggressive LDL-C targets . In this context , we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin ( niacin ER ) , a statin plus ezetimibe , and a highly potent statin alone . This was an open-label , multicenter , 12-week study in 292 patients ( 50 % women ) who qualified for drug therapy based on number of CHD risk factors . Patients were r and omized to four parallel arms , titrated from low to moderate or high doses : atorvastatin/niacin ER , rosuvastatin/niacin ER , simvastatin/ezetimibe , or rosuvastatin alone . Baseline mean values were , for LDL-C 197 mg/dL ( 5.1 mmol/L ) , HDL-C 49 mg/dL ( 1.3 mmol/L ) , triglycerides 168 mg/dL ( 1.9 mmol/L ) . There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment . All groups lowered LDL-C by approximately 50 % or more ( range -49 to -57 % ) , achieving mean levels of 82 - 98 mg/dL ( 2.1 - 2.5 mmol/L ) . Changes in non-HDL-C ( range -46 to -55 % ) mirrored those for LDL-C and did not differ among treatment groups . Statin/niacin ER combination regimens also increased HDL-C and large HDL ( HDL2 ) and lowered triglycerides and lipoprotein ( a ) significantly more than other regimens . No drug-related myopathy or hepatotoxicity was observed . In this study , low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD AIM There have been few comparisons between rosuvastatin and other statins in Japanese patients . This open-label , r and omized , parallel-group comparative study was performed to compare the efficacy and safety of rosuvastatin ( 5 mg ) and atorvastatin ( 10 mg ) once daily in Japanese patients with hypercholesterolemia . METHODS Patients with hypercholesterolemia who had received atorvastatin ( 10 mg/day ) for at least 4 weeks and were in category B3 , B4 , or C according to the Japan Atherosclerosis Society Guidelines for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases 2002 ( JAS2002GL ) were r and omly assigned to rosuvastatin at 5 mg/day ( switched treatment ) or atorvastatin at 10 mg/day ( continued treatment ) . The primary endpoint was the achievement of JAS2002GL LDL-C goals at 8 weeks . RESULTS LDL-C goals were reached by 80.3 % of the rosuvastatin group and 67.3 % of the atorvastatin group at 8 weeks ( p<0.01 ) . The percent change of the LDL-C and LDL-C/HDL-C ratio at 8 weeks was significantly greater in the rosuvastatin group than in the atorvastatin group ( both p<0.01 ) . Furthermore , rosuvastatin improved fasting plasma glucose ( p<0.01 ) . Both drugs were well tolerated . CONCLUSION Rosuvastatin ( 5 mg/day ) is a useful treatment option for high-risk patients with hypercholesterolemia BACKGROUND AND AIMS Substantial residual cardiovascular risks remain despite intensive statin treatment . Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins . K-877 ( pemafibrate ) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy . The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment . METHODS The objectives were investigated in two , multicentre , r and omised , double-blind ,  placebo-controlled  , parallel group comparison clinical trials : ( A ) K-877 0.1 , 0.2 , and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients , ( B ) K-877 0.2 ( fixed dose ) and 0.2 ( 0.4 ) ( conditional up-titration ) mg/day in combination with any statin for 24 weeks in 423 patients . RESULTS In both studies , we found a robust reduction in fasting triglyceride levels by approximately 50 % in all combination therapy groups , which was significant compared to the statin-monotherapy ( placebo ) groups ( p < 0.001 ) . High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy , i.e. small low-density lipoproteins decreased whereas larger ones increased , and larger high-density lipoproteins decreased whereas smaller ones increased . The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies . CONCLUSIONS These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment 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 Co-administration of a fibrate and statin is an effective treatment option for patients with multiple lipid abnormalities , yet adequate long-term safety and efficacy data are lacking . OBJECTIVE To evaluate the long-term safety and efficacy of fenofibric acid combined with statins in adults with mixed dyslipidemia . METHODS Three large , 12-week , phase three , double-blind , r and omized , controlled trials evaluated fenofibric acid 135 mg combined with a low- or moderate-dose statin compared to fenofibric acid or statin monotherapy , and a subsequent 52-week open-label extension study evaluated fenofibric acid 135 mg combined with moderate-dose statin ( rosuvastatin 20 mg , simvastatin 40 mg , or atorvastatin 40 mg ) . This prespecified analysis integrated results from these studies to assess the long-term safety and efficacy of combination therapy . RESULTS Across the controlled studies and the extension study , 2201 patients received at least one dose of fenofibric acid + statin  for a median duration of 364 days . The most common adverse events were headache , upper respiratory tract infection , nasopharyngitis , and back pain , with the incidence of all adverse events being similar across all combination therapy treatment groups . Rhabdomyolysis or treatment-related death was not reported in any group . Combination therapy result ed in sustained improvements in multiple lipid parameters , including triglycerides , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , non-high-density lipoprotein cholesterol , very low-density lipoprotein cholesterol , total cholesterol , apolipoprotein B , and high-sensitivity C-reactive protein . CONCLUSION Long-term fenofibric acid + statin combination therapy was generally well tolerated and result ed in comprehensive and sustained improvements in multiple lipid parameters in adults with mixed dyslipidemia BACKGROUND Statins are the most commonly prescribed drugs to reduce cardiometabolic risk . Besides the well-known efficacy of such compounds in both preventing and treating cardiometabolic disorders , some patients experience statin-induced side effects . We hypothesize that the use of natural bergamot-derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values . The aim of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction ( BPF ) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia . METHODS A prospect i ve , open-label , parallel group , placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was design ed . Patients were r and omly assigned to a control group receiving placebo ( n=15 ) , two groups receiving orally administered rosuvastatin ( 10 and 20mg/daily for 30 days ; n=16 for each group ) , a group receiving BPF alone orally ( 1000 mg/daily for 30 days ; n=15 ) and a group receiving BPF ( 1000 mg/daily given orally ) plus rosuvastatin ( 10mg/daily for 30 days ; n=15 ) . RESULTS Both doses of rosuvastatin and BPF reduced total cholesterol , LDL-C , the LDL-C/HDL-C ratio and urinary mevalonate in hyperlipidemic patients , compared to control group . The cholesterol lowering effect was accompanied by reductions of malondialdehyde , oxyLDL receptor LOX-1 and phosphoPKB , which are all biomarkers of oxidative vascular damage , in peripheral polymorphonuclear cells . CONCLUSIONS Addition of BPF to rosuvastatin significantly enhanced rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone . This lipid-lowering effect was associated with significant reductions of biomarkers used for detecting oxidative vascular damage , suggesting a multi-action enhanced potential for BPF in patients on statin therapy Summary Aim We aim ed to compare the effects of fixed‐dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia , including a subgroup analysis of patients with diabetes mellitus ( DM ) or metabolic syndrome ( MetS ) . Method This multicenter eight‐week r and omized double‐blind phase III study evaluated the safety and efficacy of fixed‐dose combinations of ezetimibe 10 mg plus rosuvastatin , compared with rosuvastatin alone in patients with primary hypercholesterolemia . Four hundred and seven patients with primary hypercholesterolemia who required lipid‐lowering treatment according to the ATP III guideline were r and omized to one of the following six treatments for 8 weeks : fixed‐dose combinations with ezetimibe 10 mg daily plus rosuvastatin ( 5 , 10 , or 20 mg daily ) or rosuvastatin alone ( 5 , 10 , or 20 mg daily ) . Results Fixed‐dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol , total cholesterol , and triglyceride levels compared with rosuvastatin alone . Depending on the rosuvastatin dose , these fixed‐dose combinations of ezetimibe plus rosuvastatin  provided LDL cholesterol , total cholesterol , and triglyceride reductions of 56%–63 % , 37%–43 % , and 19%–24 % , respectively . Moreover , the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non‐DM or non‐MetS patients , respectively , whereas the effect of rosuvastatin alone did not differ between DM vs non‐DM or MetS vs non‐MetS patients . Conclusion Fixed‐dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy  to rosuvastatin alone in lowering LDL cholesterol , total cholesterol , and triglyceride levels . Moreover , the reduction rate was greater in patients with DM or 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 ABSTRACT Objectives : In a 24-week , open-label , r and omized , parallel-group study , we compared the efficacy and metabolic effects , beyond low density lipoprotein cholesterol (LDL-C)-lowering , of atorvastatin ( ATV ) and rosuvastatin ( RSV ) in cardiovascular diseasefree subjects with primary hyperlipidaemia , treated to an LDL-C target ( 130 mg/dL ) . Methods : After a 6‐week dietary lead-in period , patients were r and omized to RSV 10 mg/day ( n = 60 ) or ATV 20 mg/day ( n = 60 ) . After 6 weeks on treatment the dose of the statin was increased ( to RSV 20 mg/day or ATV 40 mg/day ) if the treatment goal was not achieved . A control group of healthy volunteers ( n = 60 ) was also included for the validation of baseline serum and urinary laboratory parameters . The primary outcome was the percentage of patients reaching the LDL‐C goal ; secondary outcomes were changes in lipid and non-lipid metabolic parameters . Results : A total of 45 patients ( 75.0 % ) in the RSV-treated group and 43 ( 71.7 % ) in the ATV-treated group achieved the treatment target at the initial dose . Both regimens were generally well tolerated and there were no withdrawals due to treatment-related serious adverse events . Similar significant reductions in total cholesterol , LDL‐C , apolipoprotein ( apo ) B , triglycerides , apoB/apoA1 ratio , fibrinogen and high-sensitivity C‐reactive protein levels were seen . RSV had a significant high density lipoprotein cholesterol (HDL‐C)-raising effect and showed a trend towards increasing apoA1 levels . Glycaemic control and renal function parameters were not influenced by statin therapy . ATV , but not RSV , showed a significant hypouricaemic effect . Conclusions : RSV and ATV were equally efficacious in achieving LDL‐C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration . RSV seems to have a significantly higher HDL‐C-raising effect , while ATV lowers serum uric acid levels Background Statins are frequently administered to reduce low-density lipoprotein cholesterol ( LDL-C ) and vascular inflammation , because LDL-C and high sensitive C-reactive protein ( hs-CRP ) are associated with high risk for cardiovascular events . When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease ( CAD ) , ezetimibe can be added or the statin dose can be increased . However , which strategy is more effective for treating patients with CAD has not been established . The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients . Methods 46 patients with high-risk CAD and LDL-C and hs-CRP levels of > 70 mg/dL and > 1.0 mg/L , respectively , that were not improved by 4 weeks of rosuvastatin ( 2.5 mg/day ) were r and omly assigned to receive 10 mg ( R10 , n = 24 ) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe ( R2.5/E10 , n = 22 ) for 12 weeks . The primary endpoint was a change in hs-CRP . Results Baseline characteristics did not significantly differ between the groups . At 12 weeks , LDL-C and inflammatory markers ( hs-CRP , interleukin-6 , tumour necrosis factor-alpha and pentraxin 3 ) also did not significantly differ between the two groups ( LDL-C : R10 vs. R2.5/E10 : -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL ) . However , high-density lipoprotein cholesterol ( HDL-C ) was significantly improved in the R10 , compared with R2.5/E10 group ( 4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL ; p < 0.05 ) . Conclusion Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin . However , R10 elevated HDL-C more effectively than R2.5/E10.Trial registration BACKGROUND Co-administration of niacin with statin offers the potential for additional lipid management and cardiovascular risk reduction . However , niacin is underutilised because of the side effects of flushing , mediated primarily by prostagl and in D(2 ) ( PGD(2 ) ) . A combination tablet containing extended-release niacin and laropiprant ( ERN/LRPT ) , a PGD(2 ) receptor ( DP1 ) antagonist , offers improved tolerability . This study assessed the efficacy and safety of ERN/LRPT added to statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia who were not at their National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol ( LDL-C ) goal based on their coronary heart disease risk category ( high , moderate or low ) . METHODS After a 2- to 6-week run-in statin ( simvastatin 10 or 20 mg or atorvastatin 10 mg ) period , 1216 patients were r and omised equally to one of two treatment groups in a double-blind fashion : group 1 received ERN/LRPT ( 1 g ) plus the run-in statin dose and advanced to ERN/LRPT ( 2 g ) after 4 weeks for an additional 8 weeks , with no adjustments to the run-in statin dose ; group 2 received simvastatin or atorvastatin at twice their run-in statin dose and remained on this stable dose for 12 weeks . RESULTS ERN/LRPT added to statin ( pooled across statin and statin dose ) significantly improved key lipid parameters vs. the doubled statin dose ( pooled ) : the between-treatment group difference in least squares mean per cent change [ 95 % confidence interval ( CI ) ] from baseline to week 12 in LDL-C ( primary end-point ) was -4.5 % ( -7.7 , -1.3 ) and in high-density lipoprotein cholesterol ( HDL-C ) was 15.6 % ( 13.4 , 17.9 ) and in median per cent change for triglyceride ( TG ) was -15.4 % ( -19.2 , -11.7 ) . Treatment-related adverse experiences ( AEs ) related to flushing , pruritis , rash , gastrointestinal upset and elevations in liver transaminases and fasting serum glucose occurred more frequently with ERN/LRPT added to statin vs. statin dose doubled . CONCLUSIONS The addition of ERN/LRPT to ongoing statin treatment produced significantly improved lipid-modifying benefits on LDL-C , HDL-C and TG and all other lipid parameters compared with doubling the statin dose in patients with primary hypercholesterolaemia or mixed dyslipidaemia . The types of AEs that occurred at a greater frequency in the ERN/LRPT group were those typically associated with niacin Background Statin-fibrate combination therapy has been used to treat patients with acute coronary syndrome ( ACS ) complicated by elevated triglycerides ( TG ) and decreased high density lipoprotein cholesterol ( HDL-C ) . The purpose of this study was to evaluate the influence of the combination therapy on lipids profile and apolipoprotein A5 ( apoA5 ) level in patients with ACS . Methods One hundred and four patients with ACS were recruited and r and omly assigned into two groups : one was statin group ( n = 52 ) , given atorvastatin ( 20 mg QN ) or other statins with equivalent dosages ; the other was combination group ( n = 52 ) , given the same dose of statin plus bezafibrate ( 200 mg BID ) . Follow-up visits were scheduled at the end of 6 and 12 weeks post treatment . Serum apoA5 levels were determined using a commercial available ELISA kit . Results ( 1 ) Compared with that of statin monotherapy , statin-bezafibrate combination treatment not only result ed in a significant reduction of TG , TC and LDL-C levels , ( all p < 0.05 ) , but also led to increases in HDL-C and apoA5 levels ( p < 0.05).(2 ) The percentage changes of TC , TG , LDL-C and apoA5 levels in both groups were even bigger at 12 weeks after treatment than that at 6 weeks ( all p < 0.05 ) . Similarly , the rates of achieving lipid-control target were higher in statin-bezafibrate combination treatment group than those in statin monotherapy group ( all p < 0.05).(3 ) Spearman rank correlation analysis showed that the pre-treatment apoA5 level was positively correlated with TG ( r = 0.359 , p = 0.009 ) . However , a negative correlation was observed between apoA5 and TG ( r = -0.329 , p = 0.017 ) after 12 weeks treatment . Conclusions Statin and fibrate combination therapy is more effective than statin alone in achieving a comprehensive lipid control for ACS patients .  Serum apoA5 elevation after statin and fibrate combination treatment could be due to the synergistic effect of both drugs on hypertriglyceridemia control Hyperlipidemia can be effectively treated either with niacin or HMG-CoA reductase inhibitor ( statin ) , or a combination of both . Few reports showed the effects of the combination regimen with niacin and statin on hemostatic functions . We conducted a single-center , double-blind , double-dummy , r and omized , two-arm study to assess the effects of the niacin extended-release/lovastatin therapy in a fixed-dose formulation and of simvastatin on lipid lowering and two fibrinolytic parameters , fibrinogen and d-dimer .  All patients were enrolled according to NCEP-ATP III guidelines and underwent a placebo run-in period of 4 weeks before being r and omized to either niacin extended-release/lovastatin tablets ( 500/20 mg ) once daily ( n = 36 ) or simvastatin capsule ( 20 mg ) once daily ( n = 34 ) . After 16 weeks of treatment , both groups of patients showed significantly reduced low-density lipoprotein cholesterol and total cholesterol ( LDL-C , p < 0.001 and < 0.001 , respectively , p = 0.159 between the groups ; TC , p < 0.001 and < 0.001 , respectively , p = 0.018 between the groups ) . Both drugs were well tolerated . Only in the group treated with niacin extended-release/lovastatin was fibrinogen concentration significantly reduced after treatment ( 2.48 + /- 0.65 to 1.99 + /- 0.62 g/L , p = 0.008 ) . No difference was found with d-dimer in either group . This study shows that both niacin extended-release/lovastatin and simvastatin are effective and well-tolerated lipid-lowering drugs in Taiwanese patients with dyslipidemia . A combinational treatment with niacin extended-release/lovastatin may provide additional benefit in fibrinolysis
Similar trends were observed for changes in total cholesterol .
Implication sGiven the available data , the addition of ezetimibe to ongoing simvastatin , atorvastatin , or rosuvastatin monotherapy offers greater reduction in LDL-C among patients at high risk of CVD compared to doubling the initial statin dose
Purpose While statins are used as first-line treatments for high-risk patients with hypercholesterolemia , statin monotherapy is often insufficient to achieve target low-density lipoprotein cholesterol ( LDL-C ) levels .
Second-line treatment options include up-titration of statin dose , switching to a more potent statin , or combination therapy , e.g. , with ezetimibe .
The aim of this study was to evaluate the efficacy of adding ezetimibe to simvastatin , atorvastatin , or rosuvastatin monotherapy versus doubling the dosage or switching to a higher-potency statin in a population of patients with hypocholesterolemia at high risk of cardiovascular disease ( CVD ) and who had been previously treated with a statin .