Effect of morning versus evening intake of simvastatin on the serum cholesterol level in patients with coronary artery disease. The Evening versus Morning Polypill Utilization Study: the TEMPUS rationale and design Efficacy and Safety of Fluvastatin-Extended Release in Hypercholesterolemic Patients: Morning Administration Is Equivalent to Evening Administration Comparison of Effects of Morning Versus Evening Administration of Ezetimibe/Simvastatin on Serum Cholesterol in Patients with Primary Hypercholesterolemia Time-of-intake (morning versus evening) of extended-release fluvastatin in hyperlipemic patients is without influence on the pharmacodynamics (mevalonic acid excretion) and pharmacokinetics. Effect of atorvastatin on the incidence of acute kidney injury following valvular heart surgery: a randomized, placebo-controlled trial Taking simvastatin in the morning compared with in the evening: randomised controlled trial Understanding the effects of a decentralized budget on physicians' compliance with guidelines for statin prescription – a multilevel methodological approach Efficacy and safety of morning versus evening dose of controlled-release simvastatin tablets in patients with hyperlipidemia: a randomized, double-blind, multicenter phase III trial. Effect of Ezetimibe on LDL-C Lowering and Atherogenic Lipoprotein Profiles in Type 2 Diabetic Patients Poorly Controlled by Statins N-3 fatty acid supplementation to routine statin treatment inhibits platelet function, decreases patients’ daytime blood pressure, and improves inflammatory status Prevalence of Dyslipidemia and Lipid Goal Attainment in Statin-Treated Subjects From 3 Data Sources: A Retrospective Analysis Lipid lowering efficacy between morning and evening simvastatin treatment: a randomized double-blind study. Lack of evidence of a clopidogrel-statin interaction in the CHARISMA trial. Pharmacodynamic effects and pharmacokinetics of a new HMG-CoA reductase inhibitor, rosuvastatin, after morning or evening administration in healthy volunteers. Intervention to improve adherence to lipid-lowering medication and lipid-levels in patients with an increased cardiovascular risk. The influence of simvastatin on selected inflammatory markers in patients with chronic obstructive pulmonary disease. Long-term safety and efficacy of fenofibric acid in combination with statin therapy for the treatment of patients with mixed dyslipidemia. Statin use and risk of delirium in the critically ill. Effects of pioglitazone on lipid and lipoprotein profiles in patients with type 2 diabetes and dyslipidaemia after treatment conversion from rosiglitazone while continuing stable statin therapy A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease Lipid-independent effects of statins on endothelial function and bioavailability of nitric oxide in hypercholesterolemic patients. Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.
S imvastatin , as well as most of the other statins , is recommended given as a single dose in the evening . This is due to the diurnal variation in liver cholesterol synthesis peaking at nighttime and the short elimination half-life of the major active metabolite , which is 1.9 hours for simvastatin . The clinical documentation to verify this recommendation is scant . Saito et al found significant ( p 0,05 ) differences in the effects of simvastatin when the time of drug ingestion was altered between morning and evening intake . They administered doses of 2.5 and 5.0 mg , which are far lower than recommended doses today . Clinical trials comparing morning and evening intake of current dosing have , to our knowledge , not been performed . There is strong evidence that statins possess properties beyond lipid-lowering effects , such as effects on immune activation , endothelial function , and thrombosis . To compare the effects of evening versus morning intake of statins , patients with stable coronary artery disease were enrolled in a r and omized , crossover study examining the effects on lipids and high , sensitive C-reactive protein ( hs-CRP ) Background and rationale In clinical practice , blood pressure (BP)-lowering agents are generally prescribed for use in the morning , whereas ( short-acting ) statins are recommended for use in the evening . There is evidence that the reduction in LDL cholesterol ( LDL-c ) achieved with short-acting statins is superior when taken in the evening and reported improvement in BP control when aspirin and BP-lowering agents are taken in the evening . However , it is unclear whether the additional reduction in LDL-c and BP is offset by a reduction in adherence , given that taking medication in the evening may be less typical or convenient . There is therefore uncertainty concerning the best timing of administration of a cardiovascular combination pill such as the polypill . Aim The aim of TEMPUS ( NCT01506505 ) , a prospect i ve r and omized open blinded endpoint ( PROBE ) crossover trial , is to evaluate whether there is a difference in LDL-c levels or 24-hour ambulatory BP in individuals at increased risk of cardiovascular disease when the cardiovascular polypill is taken in the evening compared to the morning . An additional aim is to assess the effect of the polypill on LDL-c and BP compared to the administration of separate pills of identically dosed components of the polypill . Methods In total 75 participants with established cardiovascular disease or an intermediate to high risk for cardiovascular disease are r and omly allocated to the sequence of three different treatments of 6–8 weeks : ( 1 ) the cardiovascular polypill ( aspirin 75 mg , simvastatin 40 mg , lisinopril 10 mg , and hydrochlorothiazide 12.5 mg ) in the evening ; ( 2 ) the polypill in the morning ; and ( 3 ) the use of the identically dosed agents in separate pills taken at different time points during the day . The primary endpoint is the difference in LDL-c and mean 24-hour ambulatory systolic BP . Secondary outcomes are the difference in relative risk reduction , biochemistry , platelet function and pulse wave analysis , participants ’ adherence , and acceptability . Conclusions TEMPUS will evaluate the effect of timing of the administration of a cardiovascular polypill on LDL-c and BP measurements in patients with an intermediate or high risk for cardiovascular disease Background : Flexibility in the time of administration of statin therapy is likely to improve patient compliance . This study compared the efficacy and tolerability of morning and evening administration of the extended-release formulation of fluvastatin ( fluvastatin XL ) . Methods : In this prospect i ve , double-blind , multicenter , multiple dose study , 236 patients with type IIa/b hypercho lesterolemia were r and omized to receive fluvastatin XL , 80 mg , in the morning or evening for 8 weeks . Results : At 8 weeks , low-density lipoprotein cholesterol levels were reduced by 34.5 and 35.0 % in the morning and evening treatment groups , respectively ( p = 0.0118 for non-inferiority of morning administration ) . There were no statistically significant differences between the morning and evening treatment groups in the changes in total cholesterol ( p = 0.56 ) , high-density lipoprotein cholesterol ( p = 0.21 ) , triglycerides ( p = 0.13 ) , apolipoprotein B ( p = 0.66 ) and apolipoprotein AI ( p = 0.88 ) at 8 weeks . The frequency of adverse events was slightly lower in the morning treatment group compared with the evening treatment group ( 27.4 vs. 35.5 % ) . Conclusions : The efficacy and safety profiles of fluvastatin XL are equivalent for morning and evening administration 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 OBJECTIVE Statins inhibit the rate-limiting step in cholesterol bio synthesis , the conversion of 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) to mevalonate by HMG-CoA reductase . Statins are usually taken in the evening as the HMG-CoA reductase activity is high during the night . This recommendation might not apply if statins are given as extended-release ( ER ) formulations . The present study investigated the influence of time of intake of fluvastatin 80 mg ER on cholesterol bio synthesis . Main objectives were to measure the change in 24-hour urinary mevalonic acid excretion , to determine plasma concentrations of mevalonic acid and fluvastatin and to monitor triglycerides , total cholesterol , HDL-cholesterol and LDL-cholesterol . METHODS This was a r and omized , 2-period crossover study in 26 hypercholesterolemic patients who received a single daily dose of fluvastatin both in the morning and in the evening . RESULTS At baseline , the amount of mevalonic acid was 204.9 + /- 68.1 microg/g creatinine . After a single dose of fluvastatin  mean urine values of mevalonate were significantly reduced to 129.8 + /- 66.2 micro/g ( evening ) and to 118.7 + /-34.3 microg/g ( morning ; n.s . between groups ) , thus representing a reduction of about 39 % . Compared to baseline , plasma mevalonate concentrations were decreased by fluvastatin result ing in similar 24-hour profiles after the morning and the evening dosage . The pharmacokinetics of  fluvastatin were similar in both periods of the study , with higher plasma concentrations for several hours following the evening dosage . CONCLUSION This study demonstrates that fluvastatin ER is equally effective in inhibiting cholesterol bio synthesis when given once daily in the morning and once daily in the evening Purpose Statins , 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors have the potential to reduce acute kidney injury ( AKI ) after cardiac surgery through their pleiotropic properties . Here we studied the preventive effect of atorvastatin on AKI after valvular heart surgery . Methods Two-hundred statin-naïve patients were r and omly allocated to receive either statin or placebo . Atorvastatin was administered orally to the statin group according to a dosage schedule ( 80 mg single dose on the evening prior to surgery ; 40 mg on the morning of surgery ; three further doses of 40 mg on the evenings of postoperative days 0 , 1 , and 2 ) . AKI incidence was assessed during the first 48 postoperative hours on the basis of Acute Kidney Injury Network criteria . Results The incidence of AKI was similar in the statin and control groups ( 21 vs. 26 % , respectively , p = 0.404 ) . Biomarkers of renal injury including plasma neutrophil gelatinase-associated lipocalin and interleukin-18 were also similar between the groups . The statin group required significantly less norepinephrine and vasopressin during surgery , and fewer patients in the statin group required vasopressin . There were no significant differences in postoperative outcomes . Conclusions Acute perioperative statin treatment was not associated with a lower incidence of AKI or improved clinical outcome in patients undergoing valvular heart surgery . ( Clinical Trials.gov NCT01909739 ) Statins are widely prescribed for the primary and secondary prevention of coronary artery disease . They act by inhibiting the enzyme HMG CoA reductase , which controls synthesis of cholesterol in the liver . Most manufacturers of statins recommend that they are taken at night , on the basis of physiological studies which show that most cholesterol is synthesis ed when dietary intake is at its lowest.1 One small clinical trial found that taking smaller doses of simvastatin than are used in treatment , in the morning , was less efficient.2 However , a trial using atorvastatin found no significant difference in cholesterol concentrations between patients taking the statin in the morning and those taking it in the evening.3 Doubt has been cast on whether statins need to be taken at night,4 particularly as many patients also receive treatment with other cardioprotective drugs and compliance may be compromised by multiple Background Official guidelines that promote evidence -based and cost-effective prescribing are of main relevance for obvious reasons . However , to what extent these guidelines are followed and their conditioning factors at different levels of the health care system are still insufficiently known . In January 2004 , a de central ized drug budget was implemented in the county of Scania , Sweden . Focusing on lipid-lowering drugs ( i.e. , statins ) , we evaluated the effect of this intervention across a 25-month period . We expected that increased local economic responsibility would promote prescribing of recommended statins . Methods We performed two separate multilevel regression analyses ; on 110 827 individual prescriptions issued at 136 publicly-administered health care centres ( HCCs ) nested within 14 administrative areas ( HCAs ) , and on 72 012 individual prescriptions issued by 115 privately-administered HCCs . Temporal trends in the prevalence of prescription of recommended statins  were investigated by r and om slope analysis . Differences ( i.e. , variance ) between HCCs and between HCAs were expressed by median odds ratio ( MOR ) . Results After the implementation of the de central ized drug budget , adherence to guidelines increased continuously . At the end of the observation period , however , practice variation remained high . Prescription of recommended statins presented a high degree of clustering within both publicly ( i.e. , MORHCC = 2.18 and MORHCA = 1.31 respectively ) and privately administered facilities ( MORHCC = 3.47 ) . Conclusion A de central ized drug budget seems to promote adherence to guidelines for statin prescription . However , the high practice differences at the end of the observation period may reflect inefficient therapeutic traditions , and indicates that rational statin prescription could be further improved BACKGROUND Flexibility in the recommended dosing time for a statin may improve patient compliance . OBJECTIVE This study was design ed to compare the efficacy and tolerability of morning and evening doses of controlled-release simvastatin in Korean adults with dyslipidemia . It was carried out as a requirement to obtain authorization from the Korean regulatory agency to market the product . METHODS In this prospect i ve , r and omized , double-blind , multicenter , placebo-controlled Phase III study , we r and omly assigned 132 patients with hypercholesterolemia to a morning-dose group or an evening-dose group . Patients in the morning-dose group received 20 mg controlled-release simvastatin in the morning and a placebo in the evening , and those in the evening-dose group received a placebo in the morning and 20 mg controlled-release simvastatin in the evening . RESULTS After 8 weeks of the treatment , the difference in the mean change of LDL-C between the morning-dose and evening-dose groups was -2.78 % ( 95 % confidence interval , -7.65 to 2.10 ) . The changes in total cholesterol , triglycerides , HDL-C , apolipoprotein A1 , apolipoprotein B , and lipoprotein ( a ) after treatment did not differ between groups . Also , the achievement rates of the target LDL-C goal suggested by the dyslipidemia treatment guideline of the Korean Society of Lipidology and Atherosclerosis were not different . No serious adverse event was observed in either group . Mild and moderate adverse events were observed similarly in both groups . CONCLUSIONS Although controlled-release simvastatin significantly reduces LDL-C levels with good tolerability in Korean adults with dyslipidemia , the time of administration does not affect its efficacy Background There exists a sub population of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C , representing a major risk of CVD . The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks . Methods Lipid changes were assessed in a r and omized , multicenter , 12-week , open-label study comparing a high-potency statin ( 10 mg of atorvastatin or 1 mg of pitavastatin ) plus ezetimibe ( EAT : n = 53 ) with a double dose of statin ( 20 mg of atorvastatin or 2 mg of pitavastatin ) ( DST : n = 56 ) in DM subjects who had failed to achieve the optimal LDL-C targets .  Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C ( remnant like particle cholesterol ) and sd-LDL-C , two characteristic atherogenic risks of DM . Results The reduction of LDL-C ( % ) , the primary endpoint , differed significantly between the two groups ( -24.6 in EAT vs. -10.9 in DST ) . In the analyses of the secondary endpoints , EAT treatment brought about significantly larger reductions in sd-LDL-C ( -20.5 vs. -3.7 ) and RLP-C ( -19.7 vs. + 5.5 ) . In total , 89.4 % of the patients receiving EAT reached the optimized treatment goal compared to 51.0 % of the patients receiving DST . The changes in TC ( -16.3 vs. -6.3 ) and non-HDL-C ( -20.7 vs. -8.3 ) differed significantly between the two groups . Conclusion Ezetimibe added to high-potency statin ( 10 mg of atorvastatin or 1 mg of pitavastatin ) was more effective than the intensified-dose statin ( 20 mg of atorvastatin or 2 mg of pitavastatin ) treatment not only in helping T2DM patients attain more LDL-C reduction , but also in improving their atherogenic lipid profiles , including their levels of sd-LDL-C and RLP-C. We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response . Trial Registration The UMIN Clinical Trials Registry Objectives N-3 fatty acids reduce the risks of cardiovascular morbidity and mortality . Administration of N-3 fatty acids to patients treated with statins  may potentiate the treatment effects . We examined the operating mechanisms underlying such a combination . Methods Thirty-two hypercholesterolemic patients aged 30–70 years with hypercholesterolemia controlled by statins  , received sequential treatments with placebo followed by 1.9 g/day of N-3 fatty acids for 23 weeks . Scheduled clinical visits included physical examination , 24-h blood pressure measurement , endothelial function evaluated by pulse wave analysis , analyses for platelet function , inflammation markers [ interleukin (IL)-6 , plasminogen activator inhibitor-1 ( PAI-1 ) ] and oxidative stress parameters ( STAT-8-Isoprostane ) were undertaken at baseline , after placebo treatment , and after 6 and 20 weeks of N-3 fatty acid intake . Results Platelets functions were significantly inhibited , whereas endothelial function parameters were unaltered . IL-6 significantly decreased whereas PAI-1 and STAT-8-Isoprostane levels remained unaffected . Daytime blood pressure significantly decreased ; however , nighttime pressure and heart rate remained unchanged . No evidence of lipid-profile improvement was observed following combined treatment with statins and N-3 fatty acids . Conclusions In hypercholesterolemic patients , combination of statins and N-3 fatty acid inhibits platelet aggregation , alters inflammatory status , and positively affects daytime blood pressure . Close long-term follow-up might reveal additional beneficial effects of N-3 fatty acids in this patient population Background Evidence -based r and omized clinical trials have shown significant benefit of statin treatment with regard to cardiovascular disease . In anticipation of the National Cholesterol Education Program Adult Treatment Panel IV guidelines , we wanted to assess the current state of lipid goal attainment in the high-risk secondary prevention population in the United States . The objectives of the study were to estimate the proportion of high-risk patients treated with statin monotherapy  who achieved Adult Treatment Panel III – recommended low-density lipoprotein cholesterol ( LDL-C ) goals ( < 100 mg/dL ; optional < 70 mg/dL ) as well as non – high-density lipoprotein cholesterol goals ( < 130 mg/dL ; optional < 100 mg/dL ) . Methods and Results This is a cross-sectional , retrospective study of 3 data sources : electronic medical records ( 2003–September 2010 ) , administrative cl aims data ( 2003–2010 ) , and National Health and Nutrition Examination Survey data ( 2007–2008 ) . High-risk patients ( ≥18 years of age ) were defined as those with a history of coronary heart disease or coronary heart disease risk equivalent who had the latest complete lipid panel measurement and had been treated with statin monotherapy for > 90 days at the time of the lipid panel . Cardiovascular disease , coronary heart disease , and coronary heart disease risk equivalents were defined on the basis of availability , specific to each data source . Across the 3 data sources , 20 % to 26 % of high-risk patients treated with statin monotherapy for > 90 days had LDL-C < 70 mg/dL , and 67 % to 77 % had LDL-C < 100 mg/dL. The percentages of those attaining both LDL-C goals and non – high-density lipoprotein cholesterol goals were quantitatively smaller ( 13.5 % to 19.0 % and 46 % to 70 % ) . Conclusions Across the 3 data sources , there was consistency in the proportion of high-risk patients treated with statin monotherapy who were at LDL-C goal . A significant number of these statin-treated patients had additional dyslipidemias OBJECTIVES To compare lipid-lowering efficacy and high sensitive C-reactive protein ( hsCRP ) level between morning and evening simvastatin administration in hyperlipidemia subjects . MATERIAL AND METHOD A r and omized double blind controlled trial was conducted in 52 dyslipidemia subjects . A group of twenty five subjects received 10 mg simvastatin in the morning and placebo in the evening . The other group of twenty seven subjects received vice versa . Serum lipid profiles were evaluated every 4 weeks for the total course of 12 weeks . High sensitive CRP was measured at the beginning and the end of the study . RESULTS Baseline LDL levels were similar in both groups ( p = 0.95 ) . The evening simvastatin group had significantly less low density lipoprotein level ( LDL ) than the morning group at 4 weeks ( 112 + /- 26.1 mg/dl vs. 136.3 + /- 32 mg/dl , p = 0.001 ) and 8 weeks after treatment ( 109.7 + /- 28 mg/dl vs. 129.5 + /- 27 mg/dl , p = 0.006 ) . Difference in LDL after 12th week between two groups was not significant ( p = 0.23 ) . Triglyceride and HDL level were not different in both groups . Only evening simvastatin administration could significantly decrease hsCRP ( p = 0.03 ) . CONCLUSION Simvastatin should be taken in the evening . Although lipid profiles were not statistically different in morning and nighttime simvastatin , the inflammatory marker ( hsCRP level ) is significantly reduced as a result of evening simvastatin administration OBJECTIVES The purpose of this study was to evaluate the potential impact of clopidogrel and statin interaction in a r and omized , placebo-controlled trial with long-term follow-up . BACKGROUND There are conflicting data regarding whether statins predominantly metabolized by CYP3A4 reduce the metabolism of clopidogrel to its active metabolite and diminish its clinical efficacy . METHODS The CHARISMA trial was a r and omized trial comparing long-term 75 mg/day clopidogrel versus placebo in patients with cardiovascular disease or multiple risk factors on aspirin . The primary end point was a composite of myocardial infa rct ion , stroke , or cardiovascular death at median follow-up of 28 months . We performed a secondary analysis evaluating the interaction of clopidogrel versus placebo with statin administration , categorizing baseline statin use to those predominantly CYP3A4 metabolized ( atorvastatin , lovastatin , simvastatin ; CYP3A4-MET ) or others ( pravastatin , fluvastatin ; non-CYP3A4-MET ) . RESULTS Of 15,603 patients enrolled , 10,078 received a statin at baseline ( 8,245 CYP3A4-MET , 1,748 non-CYP3A4-MET ) and 5,496 did not . For the overall population , the primary end point was 6.8 % with clopidogrel and 7.3 % with placebo ( hazard ratio [ HR ] 0.93 ; p = 0.22 ) . This was similar among patients on CYP3A4-MET ( 5.9 % clopidogrel , 6.6 % placebo , HR 0.89 ; p = 0.18 ) or non-CYP3A4-MET statin ( 5.7 % clopidogrel , 7.2 % placebo , HR 0.78 ; p = 0.19 ) . There was no interaction between statin types and r and omized treatment ( p = 0.69 ) . Patients on atorvastatin ( n = 4,127 ) ( 5.7 % clopidogrel , 7.1 % placebo , HR 0.80 ; p = 0.06 ) or pravastatin ( n = 1,440 ) ( 5.1 % clopidogrel , 7.0 % placebo , HR 0.72 ; p = 0.13 ) had similar event rates . CONCLUSIONS Despite theoretic concerns and ex vivo testing suggesting a potential negative interaction with concomitant clopidogrel and CYP3A4-MET statin administration , there was no evidence of an interaction clinical ly in a large placebo-controlled trial with long-term follow-up AIMS To compare the lipid-regulating effects and steady-state pharmacokinetics of rosuvastatin , a new synthetic hydroxy methylglutaryl-coenzyme A ( HMG-CoA ) reductase inhibitor , following repeated morning and evening administration in volunteers with fasting serum low-density lipoprotein cholesterol ( LDL-C ) concentrations < 4.14 mmol l-1 . METHODS In this open-label two-way crossover trial 24 healthy adult volunteers were r and omized to receive rosuvastatin 10 mg orally each morning ( 07.00 h ) or evening ( 18.00 h ) for 14 days . After a 4 week washout period , volunteers received the alternative regimen for 14 days . Rosuvastatin was administered in the absence of food . RESULTS Reductions from baseline in serum concentrations of LDL-C ( -41.3%[morning]vs-44.2%[evening ] ) , total cholesterol ( -30.9%vs-31.8 % ) , triglycerides ( -17.1%vs-22.7 % ) , and apolipoprotein B ( -32.4%vs-35.3 % ) were similar following morning and evening administration . AUC(0,24 h ) for plasma mevalonic acid ( MVA ) , an in vivo marker of HMG-CoA reductase activity , decreased by -29.9 % ( morning ) vs-32.6 % ( evening ) . Urinary excretion of MVA declined by -33.6 % ( morning ) vs-29.2 % ( evening ) . The steady-state pharmacokinetics of  rosuvastatin were very similar following the morning and evening dosing regimens . The Cmax values were 4.58 vs 4.54 ng ml-1 , and AUC(0,24 h ) values were 40.1 vs 42.7 ng ml-1 h , following morning and evening administration , respectively . There were no serious adverse events during the trial , and rosuvastatin was well tolerated after morning and evening administration . CONCLUSIONS The pharmacodynamic effects and pharmacokinetics of rosuvastatin are not dependent on time of dosing . Morning or evening administration is equally effective in lowering Low levels of statin adherence may compromise treatment outcomes . The aim of this study was to investigate whether nurse-led cardiovascular risk-factor counseling could improve statin adherence and lipid levels without increasing patients ' anxiety .  Patients with indications for statin therapy for primary or secondary prevention of cardiovascular disease were r and omly assigned to receive routine care or extended care ( EC ) at baseline and at months 3 , 9 , and 18 . Patients in the EC group received a personalized risk-factor passport , showing modifiable and unmodifiable individual risk factors and a graphical presentation of their calculated absolute 10-year cardiovascular disease risk as well as the target risk that could be reached if all modifiable risk factors were optimally treated . Lipid levels were assessed at each visit . Carotid intima-media thickness was measured at baseline and at month 18 . Adherence , anxiety , quality of life , symptoms , and smoking status were assessed using a self-administered question naire at each visit . A total of 201 patients were included in the study .  Statin adherence was significantly higher ( p < 0.01 ) and anxiety was significantly lower ( p < 0.01 ) in the EC group than in the routine care group . Low-density lipoprotein cholesterol was statistically significantly lower in the EC group than in the routine group ( 2.66 vs 3.00 mmol/L , respectively , p = 0.024 ) in primary prevention patients only . Intima-media thickness improved significantly from baseline ( p < 0.01 ) in all patients , irrespective of group assignment . In conclusion , cardiovascular risk-factor counseling result ed in improved lipid profiles in primary prevention patients and higher levels of adherence to statins and lower levels of anxiety in all patients INTRODUCTION There is growing evidence that chronic obstructive pulmonary disease ( COPD ) is a risk factor for coronary heart disease . Simvastatin is a hypolipemic drug with proven efficacy in the prevention of cardiovascular diseases . Observational studies showed that statins may be useful in the reduction of mortality from COPD . Experimental studies on animals showed anti-inflammatory effects of statins on the lung tissue . OBJECTIVES The aim of this study was to evaluate the influence of simvastatin on inflammatory markers in patients with COPD . PATIENTS AND METHODS Fifty-six patients ( aged 44 - 80 years ) with stable COPD ( a mean forced expiratory volume in 1 second [ FEV1 ] 55 % ) , were r and omly assigned ( 1:1 ) to receive simvastatin 40 mg/day or to receive no statin treatment .  Blood sample s were collected before , 2 weeks , and 3 months after statin administration . The levels of fibrinogen , C-reactive protein ( CRP ) , tumor necrosis factor-alpha , interleukin 6 ( IL-6 ) , and matrix metalloproteinase-9 were measured . RESULTS The groups did not differ significantly in terms of demographic data , clinical symptoms , pharmacological treatment , spirometry , and lipid profile at baseline . Among comorbidities only arterial hypertension was more frequent in the  statin  group ( 32.1 % vs. 17.9 % , P = 0.03 ) . After 2 weeks as well as 3 months of simvastatin treatment , no significant reduction of any measured inflammatory markers was observed . There was a nonsignificant reduction of CRP and IL-6 in the subgroup with FEV1 > 50 % during simvastatin treatment . There was a decrease in total cholesterol ( from 5.7 to 4.7 mmol/l , P = 0.0018 ) and low-density lipoprotein cholesterol ( from 3.46 to 2.47 mmol/l , P = 0.000037 ) in the statin group . CONCLUSIONS In COPD patients , a 3-month treatment with simvastatin does not reduce circulating inflammatory markers 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 RATIONALE Delirium is common in intensive care unit ( ICU ) patients and is a predictor of worse outcomes and neuroinflammation is a possible mechanism . The antiinflammatory actions of statins may reduce delirium . OBJECTIVES To determine whether critically ill patients receiving statin therapy  had a reduced risk of delirium than those not on statins .  METHODS A prospect i ve cohort analysis of data from consecutive ICU patients admitted to a UK mixed medical and surgical critical care unit between August 2011 and February 2012 ; the Confusion Assessment Method for ICU was used to determine the days each patient was assessed as being free of delirium during ICU admission . MEASUREMENTS AND MAIN RESULTS Delirium-free days , daily administration of statins , and serum C-reactive protein ( CRP ) were recorded . Four hundred and seventy consecutive critical care patients were followed , of whom 151 patients received statins .  Using r and om-effects multivariable logistic regression , statin administration the previous evening was associated with the patient being assessed as free of delirium ( odds ratio , 2.28 ; confidence interval , 1.01 - 5.13 ; P < 0.05 ) and with lower CRP ( β = -0.52 ; P < 0.01 ) the following day . When the association between statin and being assessed as free of delirium was controlled for CRP , the effect size became nonsignificant ( odds ratio , 1.56 ; confidence interval , 0.64 - 3.79 ; P = 0.32 ) . CONCLUSIONS Ongoing statin therapy is associated with a lower daily risk of delirium in critically ill patients . An ongoing clinical trial , informed by this study , is investigating if statins are a potential therapy for delirium in the critically ill 4The aim of this study was to evaluate changes in lipid profiles in patients with type 2 diabetes after treatment conversion from rosiglitazone to pioglitazone  while maintaining stable statin and other lipid-altering therapies . A total of 305 patients were enrolled in this open-label study . Patients had been taking stable dosages of rosiglitazone and statins for > 90 days . At baseline , patients discontinued rosiglitazone and started pioglitazone 30 mg/day , but continued statins and other lipid-altering therapies . The primary end point was change from baseline in fasting triglyceride levels . At 17 weeks after treatment conversion , patients had significant reductions in triglycerides ( -15.2 % ) , total cholesterol ( -9.0 % ) , and low-density lipoprotein ( LDL ) particle concentration ( -189 nmol/L ) , and increases in LDL cholesterol ( + 2.2 % ) , high-density lipoprotein ( HDL ) cholesterol ( + 1.8 % ) , and LDL particle diameter ( + 0.23 nm ) . In conclusion , after treatment conversion from rosiglitazone to pioglitazone while maintaining stable statin therapy , patients with type 2 diabetes had marked improvements in lipid profiles along with stable glycaemic control Background : Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies . Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors ( statins ) may decrease the risk of Alzheimer disease ( AD ) and a single-site trial suggested possible benefit in cognition with statin treatment in AD , supporting the hypothesis that statin therapy is useful in the treatment of AD . Objective : To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD . Methods : This r and omized , double-blind , placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels . Participants were r and omly assigned to receive simvastatin , 20 mg/day , for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo . The primary outcome was the rate of change in the Alzheimer 's Disease Assessment Scale – cognitive portion ( ADAS-Cog ) . Secondary outcomes measured clinical global change , cognition , function , and behavior . Results : A total of 406 individuals were r and omized : 204 to  simvastatin  and 202 to placebo . Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures . There was no evidence of increased adverse events with simvastatin treatment . Conclusion : Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol . Classification of evidence : This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog BACKGROUND Experimental evidence suggests a lipid-independent effect of statins on endothelial function and nitric oxide ( NO ) availability in humans . We investigated whether improvement in NO availability in hypercholesterolemia can be achieved rapidly with statins before lipid-lowering therapy is complete . METHODS We studied 41 patients ( 52 + /- 11 years ) with low-density lipoprotein ( LDL ) cholesterol > or = 130 mg/dL ( 179 + /- 45 mg/dL ) r and omly assigned to treatment either with atorvastatin ( 20 mg/day ) or cerivastatin ( 0.4 mg/day ) .  Endothelium-dependent vasodilation of the forearm vasculature was measured by plethysmography and intra-arterial infusion of acetylcholine ( ACh ) after 3 days ( n = 18 ) and 14 days ( n = 39 ) of treatment . NO availability and oxidative stress were assessed by coinfusion of l-NMMA and vitamin C. RESULTS After 3 days of treatment , LDL-cholesterol decreased by 11.9 % with a further decrease to 29.6 % after 14 days ( P < .001 ) . Endothelium-dependent vasodilation improved by + 46.7 % after 3 days of statin therapy compared with before therapy ( ACh 48 microg/min : + 15.7 + /- 10.6 vs + 10.7 + /- 10.8 mL/min per 100 mL , P < .05 ) . No further improvement in endothelium-dependent vasodilation ( + 42.7 % compared with before therapy ) could be demonstrated after 14 days of treatment ( ACh 48 microg/min : + 17.7 + /- 10.3 vs + 12.4 + /- 9.3 mL/min per 100 mL before therapy , P < .001 ) . Coinfusion of ACh plus vitamin C was able to improve endothelium-dependent vasodilation before but not after 3 or 14 days of statin therapy either . The improvement in endothelium-dependent vasodilation after therapy was no longer observed when the NO-synthase inhibitor l-NMMA was coinfused together with ACh . CONCLUSIONS Short-term lipid-lowering therapy with statins is able to improve endothelial function and NO availability almost completely after 3 days in hypercholesterolemic patients probably by decreasing oxidative stress . This improvement seems to be more rapid than the accompanying decline in LDL-cholesterol and not related to these lipid changes . This finding can support the concept of lipid-independent effects of statins in humans OBJECTIVE In addition to lowering lipid levels , statins might reduce leukocyte-endothelial cell interactions . Therefore , we assessed whether this effect could limit the inflammatory response to cardiopulmonary bypass ( CPB ) in cardiac surgical patients . METHODS Twenty patients undergoing valve or coronary operations with tepid ( 34 degrees C ) CPB were r and omized to receive an oral dose of atorvastatin ( 40 mg the evening before and 40 mg the morning of surgery ) or to serve as controls . Pre- and post-CPB blood sample s were assayed for neutrophil CD11b surface adhesion molecule and oxidative burst . Plasma levels of interleukins 6 and 8 , P-selectin , soluble intercellular adhesion molecule-1 , and lactoferrin were measured by enzyme-linked immunosorbent assay ( ELISA ) . In addition , right atrial biopsies were taken before and at the end of CPB , and processed for the expression of the transcription nuclear factor-kappa B ( NF-kappaB ) . RESULTS The two groups did not differ with regard to pre- and intraoperative data . Except for P-selectin , postbypass values of all markers significantly increased over baseline values , but atorvastatin therapy failed to attenuate the magnitude of this increase . In the two groups , the expression of NF-kappaB significantly ( p = 0.004 ) increased over baseline without group effect . Postoperative clinical outcomes did not differ either between the two groups . CONCLUSION These data show that acute preoperative statin therapy fails to limit the inflammatory response to CPB ; however , the data also document a major upregulation of NF-kappaB during cardiac operations , thereby providing a sound rationale for interventions targeted at inactivating this key component of the inflammatory cascade
LDL-C and TC lowering was significantly greater in the evening dose than in the morning dose in case of short-acting statins .
Besides slight but significant effect on LDL-C , the efficacy of long-acting statins was equivalent for both regimens .
BACKGROUND Evidence about the optimal time of day at which to administer statins is lacking .
OBJECTIVE The objective of this study is to synthesize evidence about effects of morning vs evening statin administration on lipid profile .