title: Cost-Effectiveness and Population Impact of Statins for Primary Prevention in Adults Aged 75 Years or Older in the United States Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. CHRONOKINETICS OF PRAVASTATIN ADMINISTERED IN THE PM COMPARED WITH AM DOSING Taking simvastatin in the morning compared with in the evening: randomised controlled trial Comparison between morning and evening doses of simvastatin in hyperlipidemic subjects. A double-blind comparative study. Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study. Adherence to statins in primary prevention: yearly adherence changes and outcomes. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. The Lipid Research Clinics Coronary Primary Prevention Trial Nonutilization of Statins in a Community-based Population with a History of Coronary Revascularization. Impact of better adherence to statin agents in the primary prevention of coronary artery disease Comparison of the efficacy and safety profile of morning administration of controlled-release simvastatin versus evening administration of immediate-release simvastatin in chronic kidney disease patients with dyslipidemia. Pharmacodynamic effects and pharmacokinetics of a new HMG-CoA reductase inhibitor, rosuvastatin, after morning or evening administration in healthy volunteers. Actual versus prescribed timing of lovastatin doses assessed by electronic compliance monitoring Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Steady‐state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol® XL Continuation of statin treatment and all-cause mortality: a population-based cohort study. Continuation of statin therapy and primary prevention of nonfatal cardiovascular events. 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. The use of self-measured blood pressure determinations in assessing dynamics of drug compliance in a study with amlodipine once a day, morning versus evening Comparison of a morning polypill, evening polypill and individual pills on LDL-cholesterol, ambulatory blood pressure and adherence in high-risk patients; a randomized crossover trial. Effects of morning versus evening administration of atorvastatin in patients with hyperlipidemia. Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. II. Once-daily versus twice-daily dosing. Efficacy and Safety of Fluvastatin-Extended Release in Hypercholesterolemic Patients: Morning Administration Is Equivalent to Evening Administration Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)
abstract: Editors ' Notes Context Clinical guidelines provide conflicting recommendations about whether to prescribe statins in persons aged 75 years or older for primary prevention of unwanted cardiovascular outcomes . Contribution This study used information from clinical trials to model the tradeoffs between benefits and harms and found that using  statins  in all persons aged 75 to 94 years would prevent new myocardial infa rct ions and deaths from coronary heart disease at an acceptable cost . Caution Small increases in the frequency or severity of harms would negate the benefits . Implication Additional research is warranted to better underst and the tradeoffs between benefits and harms in this age group . Statins are commonly used in adults aged 75 years or older ( 1 ) . Despite their widespread use , evidence for their effectiveness for primary prevention in elderly adults is unclear , and guidelines for their use in this population are inconsistent . The recently published American College of Cardiology/American Heart Association ( ACC/AHA ) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults gave limited recommendations for statin use for primary prevention in adults aged 75 years or older ( 2 ) , noting that few data were available to indicate an atherosclerotic cardiovascular disease event reduction benefit in primary prevention among individuals > 75 years of age who do not have clinical year atherosclerotic cardiovascular disease , and suggesting that comorbid conditions , safety , and priorities of care are recommended for joint provider and patient decision making . The American Medical Directors Association , a professional group of long-term care providers , recommended that statins not be routinely prescribed in adults aged 70 years or older as part of the American Board of Internal Medicine Choosing Wisely campaign ( 3 ) . This recommendation was based on the lack of an association between high cholesterol levels and outcomes in older adults as well as the potential for an increased risk for statin-related adverse events , including cognitive impairment , falls , neuropathy , and muscle damage ( 3 ) . The variation in these treatment recommendations reflects uncertainty about the balance between the benefits and risks of statin use in older adults compared with younger adults as well as the more limited evidence base in this population . Adults aged 75 years or older have been underrepresented in trials of statins for primary prevention , so the effectiveness of statins is less clear in this population . Results from observational studies suggest that the associations between low-density lipoprotein ( LDL ) cholesterol levels and outcomes are attenuated in older adults ( 47 ) . Although the baseline risk for cardiovascular disease is increased in older adults , their life expectancy is shorter and their risks for competing mortality are greater . Finally , there has been concern about geriatric-specific adverse effects , especially functional limitation due to muscle pain , weakness , and mild cognitive impairment ( 816 ) . In the presence of uncertainty about the riskbenefit tradeoff , computer simulations can provide estimates of the potential benefits of various treatment strategies as well as the costs and potential risk for harms . We evaluated the population benefit and cost-effectiveness of statins in persons aged 75 years or older without a history of cardiovascular disease in the United States . This investigation was conducted using the Cardiovascular Disease Policy Model ( CVDPM ) , a Markov model of the U.S. population ( 17 ) . We simulated the impact of statins for primary prevention based on treatment of the high-risk groups identified by the ACC/AHA guidelines , the associated costs , and potential harms that could offset the potential cardiovascular benefits in the U.S. population of adults aged 75 to 94 years over the next 10 years . Methods The Model The CVDPM is an established state-transition ( Markov ) model of the incidence , prevalence , mortality , and cost of CHD and stroke in U.S. residents aged 35 to 94 years ( 17 ) . The present study was limited to adults aged 75 to 94 years . The model comprises 3 components . First , the demographic-epidemiologic submodel estimates the incidence of coronary heart disease ( CHD ) ( cardiac arrest , myocardial infa rct ion [ MI ] , angina , or CHD death ) , ischemic stroke , and death from other causes on the basis of age , sex , systolic blood pressure , smoking , high-density lipoprotein and LDL cholesterol levels , diabetes , body mass index , and statin use . Second , the bridge submodel characterizes the initial CHD or stroke event and related events in the subsequent 30 days . Third , the disease-history submodel predicts the number of subsequent CHD and stroke events , revascularization procedures , and deaths among patients with cardiovascular disease , stratified according to age , sex , and history of cardiovascular disease events . In addition , persons may exit the model at any stage through a non-CHD , nonstroke mortality function , allowing for competing risk . Modifiable components of the model include population distributions , risk factor levels , risk factor coefficients , event rates , case-fatality rates , costs , and disability adjustments ( 17 ) . Costs for stroke requiring hospitalization , CHD , and acute stroke rehabilitation were estimated using California hospital data ( 18 ) and were deflated using costcharge ratios and the ratio of the U.S. national average costs to the California average ( 19 , 20 ) . Age- and sex-specific background health care costs were estimated using national data ( 21 ) . All model costs were inflated to 2014 costs by using the medical component of the Consumer Price Index ( 22 ) . All disability weights associated with the CHD and stroke event states were based on the Global Burden of Disease Study ( 23 , 24 ) . Additional details are provided in the Appendix . Simulation Inputs We modeled the effect of statins on LDL cholesterol level based on PROSPER ( Prospect i ve Study of Pravastatin in the Elderly at Risk of Vascular Disease ) , a r and omized , placebo-controlled trial of 5804 men and women aged 70 to 82 years ( 25 ) . In that trial , the mean reduction in LDL cholesterol level was 34 % for participants with an average initial level of 147 mg/dL , consistent with the estimated effect of a moderate-dose statin in the 2013 ACC/AHA guideline ( 2 ) . We included 3 estimates for the effectiveness of a decrease in LDL cholesterol level on events . The primary estimates were derived by extrapolating the age-stratified effect sizes of a 1.0-mmol/L reduction in LDL cholesterol level from the Cholesterol Treatment Trialists ' meta- analysis ( 26 ) . We fit a regression line to the 3 age strata reported in that analysis ( 60 years , > 60 to 70 years , and > 70 years ) to estimate the effect sizes at ages 80 and 90 years . In a sensitivity analysis , we used a high estimate based on the age-pooled estimate of effect of a 1.0-mmol/L reduction in LDL cholesterol level on major coronary events in the meta- analysis . We used a low estimate based on the effect size from PROSPER for primary prevention ( 25 ) . Statin costs were derived from the National Average Drug Acquisition Cost ( NADAC ) data base ( 27 ) . Our primary cost estimate ( $ 5.59 for a 30-day supply ) was the average of the NADAC costs for the 4 moderate-dose statins that are available in generic form : atorvastatin , 10 mg ; simvastatin , 20 mg ; pravastatin , 40 mg ; and lovastatin , 40 mg . This cost estimate was $ 5.00 when indexed to 2010 dollars based on the medical component of the Consumer Price Index ( 22 ) . In addition , we used a low cost estimate of $ 4 per month , based on the price of generic statins from multiple discount retailers ( such as Walmart , Target , and Walgreens ) . For a high cost estimate , we used $ 30 for a 30-day supply ; the low and high cost estimates have been used similarly in other contemporary cost-effectiveness analyses ( 28 , 29 ) . Adults aged 65 years or older use a median of 4 medications ; therefore , we estimated the cost of an additional 0.25 physician visit per year for statin use , assuming that medication management could be covered in 1 visit ( 30 , 31 ) . We estimated 1 lipid panel per year for monitoring ( 32 ) . Event rates for myopathy and hemorrhagic stroke were estimated as 0.001 per statin-year of use , based on the ACC/AHA guideline statement ( 2 ) . Although many major and minor adverse effects have been reported to be associated with statin use , we focused on 2 that are important to geriatric population s and that have generated concern in the scientific literature : functional limitation due to muscle pain and weakness , and mild cognitive impairment ( 816 ) . Both are prevalent in older adults and can have a substantial effect on quality of life and the ability to live independently . A recent review of late-life activity limitations in the United States reported data on participants in 5 nationally representative surveys . The prevalence of limitations in activities of daily living was 27 % in adults aged 75 to 84 years and 45 % in those aged 85 years or older ( 33 ) . The population -weighted average of these estimates is 32 % for adults aged 75 to 94 years . Widely varying prevalence estimates for mild cognitive impairment have been reported due to the differential measures of this condition and the differences between population s. A recent review reported prevalence of mild cognitive impairment of 19 % to 28 % in studies of older U.S. adults ; we used the average of the 4 U.S. studies , which was 25 % ( 34 ) . Disability-adjusted life-years for the corresponding states were calculated as 1 minus the disability weights reported in the Global Burden of Disease Study ( 24 ) . Because the statin-associated relative risk for these adverse effects is uncertain , we assumed no elevated risk for these adverse effects in our base-case scenario . The goal of this investigation was not to evaluate the strength of the literature regarding the presence of these adverse IMPORTANCE Most patients with cardiovascular disease ( CVD ) do not take recommended medications long-term . The use of fixed-dose combinations ( FDCs ) improves adherence in several clinical areas . Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment . OBJECTIVE To assess whether FDC delivery of aspirin , statin , and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors , systolic blood pressure ( SBP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PARTICIPANTS The UMPIRE trial , a r and omized , open-label , blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe . The trial follow-up concluded in July 2012 . INTERVENTIONS Participants were r and omly assigned ( 1:1 ) to an FDC-based strategy  ( n=1002 ) containing either ( 1 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 50 mg atenolol or ( 2 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 12.5 mg hydrochlorothiazide or to usual care ( n=1002 ) . MAIN OUTCOMES AND MEASURES Adherence to medication ( defined as self-reported use of antiplatelet , statin , and ≥2 BP-lowering medications ) and changes in SBP and LDL-C from baseline . RESULTS At baseline , mean BP was 137/78 mm Hg , LDL-C was 91.5 mg/dL , and 1233 ( 61.5 % ) of 2004 participants reported use of antiplatelet , statin , and 2 or more BP-lowering medications . Median follow-up was 15 months ( interquartile range , 12 - 18 months ) . The FDC group had improved adherence vs usual care ( 86 % vs 65 % ; relative risk [ RR ] of being adherent , 1.33 ; 95 % CI , 1.26 - 1.41 ; P < .001 ) with concurrent reductions in SBP ( -2.6 mm Hg ; 95 % CI , -4.0 to -1.1 mm Hg ; P < .001 ) and LDL-C ( -4.2 mg/dL ; 95 % CI , -6.6 to -1.9 mg/dL ; P < .001 ) at the end of the study . Although there was consistency of effects across predefined subgroups , evidence existed of larger benefits in patients with lower adherence at baseline . In this subgroup of 727 participants ( 36 % ) , adherence at the end of study was 77 % vs 23 % ( RR , 3.35 ; 95 % CI , 2.74 - 4.09 ; P < .001 for interaction ) , SBP was reduced by 4.9 mm Hg ( 95 % CI 7.3 - 2.6 mm Hg ; P = .01 for interaction ) , and LDL-C was reduced by 6.7 mg/dL ( 95 % CI , 10.5 - 2.8 mg/dL ; P = .11 for interaction ) . There were no significant differences in serious adverse events or cardiovascular events ( 50 [ 5 % ] in the FDC group and 35 [ 3.5 % ] in the usual care group ; RR , 1.45 ; 95 % CI , 0.94 - 2.24 ; P=.09 ) between the groups . CONCLUSIONS AND RELEVANCE Among patients with or at high risk of CVD , use of an FDC strategy for blood pressure , cholesterol , and platelet control vs usual care result ed in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION clinical trials.gov Identifier : NCT01057537 Pravastatin , an HMG CoA reductase inhibitor used in the treatment of hypercholesterolemia , is recommended for bedtime ( PM ) dosing . Bedtime dosing with pravastatin is slightly more efficacious but not significantly different than morning ( AM ) dosing in lowering LDL-C and total cholesterol . The pharmacokinetics of pravastatin and its major metabolite SQ 31,906 were determined in 20 healthy men administered a single 20-mg dose either in the morning or at bedtime in an open , r and omized , crossover study . Concentrations of pravastatin and SQ 31,906  were measured in serum and urine by gas chromatograph/mass spectrometry methodology . The area under the serum concentration time curve ( AUC ) of pravastatin  was significantly less ( 40 % ) following PM dosing compared with AM dosing . Urinary excretion of pravastatin  following PM dosing was also significantly decreased . Bioavailability of SQ 31,906 was somewhat higher in the PM group ( 20 % greater following PM administration ) , and urinary excretion of SQ 31,906 was significantly increased by 60 % following PM dosing . The lower AUC of pravastatin  following PM dosing does not diminish its efficacy , possibly because PM dosing immediately precedes the diurnal peak period of hepatic cholesterol synthesis . Lower blood levels of pravastatin  following PM dosing may contribute to its favorable safety profile 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 Previous studies have shown that simvastatin , a hydroxymethyl glutaryl coenzyme A reductase inhibitor , reduces plasma cholesterol levels when administered once a day . In the present study , the efficacy and tolerability of a morning and an evening dose were compared . The dosages employed were 2.5 and 5 mg for 12 weeks . This investigation was a double-blind , placebo-controlled study involving 172 hyperlipidemic subjects whose plasma cholesterol levels were higher than 220 mg/dl . During the study period , mean changes in plasma cholesterol level ( from baseline ) were -11 % with the 2.5-mg q.a.m . regimen , -15 % with the 2.5-mg q.p.m . regimen , -14 % with the 5-mg q.a.m . regimen , and -21 % with the 5-mg q.p.m . regimen . Each of these changes was statistically significant when compared with that in the placebo group ( p less than 0.001 ) . In addition , the reduction in cholesterol level was significantly greater with the evening regimen than with the morning regimen for both the 2.5-mg ( p less than 0.05 ) and the 5-mg ( p less than 0.05 ) dosages . The changes in triglyceride and high density lipoprotein cholesterol levels in each group were not significantly different from those in the placebo group . There were no differences in the incidence of clinical adverse reactions among the various treatment groups . In conclusion , when simvastatin was administered orally once per day in the evening , it reduced cholesterol levels to a significantly greater degree than when it was given in the morning BACKGROUND A controlled-release ( CR ) formulation of simvastatin was recently developed in Korea . The formulation is expected to yield a lower C(max ) and similar AUC values compared with the immediate-release ( IR ) formulation . OBJECTIVE The goal of this study was to compare the pharmacokinetics of the new CR formulation and an IR formulation of simvastatin after single- and multiple-dose administration in healthy Korean subjects . This study was developed as part of a product development project at the request of the Korean regulatory agency . METHODS This was a r and omized , open-label , parallelgroup , 2-part study . Eligible subjects were healthy male or female volunteers between the ages of 19 and 55 years and within 20 % of their ideal weight . In part I , each subject received a single dose of the CR or IR formulation of simvastatin 40 mg orally ( 20 mg x 2 tablets ) after fasting . In part II , each subject received the same dose of the CR or IR formulation for 8 consecutive days . Blood sample s were obtained for 48 hours after the dose in part I and after the first and the last dose in part II . Pharmacokinetic parameters were determined for both simvastatin ( the inactive prodrug ) and simvastatin acid ( the active moiety ) . An adverse event ( AE ) was defined as any unfavorable sign ( including an abnormal laboratory finding ) or symptom , regardless of whether it had a causal relationship with the study medication . Serious AEs were defined as any events that are considered life threatening , require hospitalization or prolongation of existing hospitalization , cause persistent or significant disability or incapacity , or result in congenital abnormality , birth defect , or death . AEs were determined based on patient interviews and physical examinations . RESULTS Twenty-four healthy subjects ( 17 men , 7 women ; mean [ SD ] age , 29 [ 7 ] years ; age range , 22 - 50 years ) were enrolled in part I , and 29 subjects ( 17 men , 12 women ; mean age , 33 [ 9 ] years ; age range , 19 - 55 years ) were enrolled in part II . For  simvastatin acid  , C(max ) was significantly smaller ( 1.68 vs 3.62 ng/mL ; P < 0.013 ) and T(max ) and apparent t((1/2 ) ) significantly longer ( 10.33 vs 4.04 hours [ P < 0.001 ] and 11.41 vs 4.16 hours [ P < 0.011 ] ) for the CR formulation compared with the IR formulation , respectively , after the single-dose administration . After the multiple-dose administration , for simvastatin acid , the C(max ) for the CR formulation was significantly smaller ( 3.40 vs 5.16 ng/mL ; P < 0.037 ) , while the values for T(max ) and apparent t((1/2 ) ) were significantly longer ( 8.40 vs 4.57 hours and 13.09 vs 4.52 hours ; both , P < 0.001 ) compared with the IR formulation . There was no significant difference between the CR and the IR formulations for AUC(0-last ) and AUC(0-infinity ) ) during either the single- or multiple-dose testing . Both CR and IR formulations were well tolerated in all subjects , and no serious AEs or adverse drug reactions were found . No subjects reported any AEs during part I of the study . During part II , 6 subjects ( 3 from each formulation group ) reported headache , 1 reported lumbago before the dose , and 1 subject had a hordeolum while receiving the CR formulation . CONCLUSIONS The C(max ) of the simvastatin CR formulation was found to be significantly smaller while the AUC of the active moiety did not differ significantly from that of the IR formulation in these healthy Korean subjects . The simvastatin CR and IR formulations were well tolerated , with no serious AEs observed . To evaluate the characteristics of the CR formulation , its clinical efficacy must be examined in patient population BACKGROUND Adherence to statins in real-world practice setting s is known to be suboptimal . However , less is known about how adherence changes over time and whether changes in adherence are associated with adverse cardiovascular ( CV ) outcomes . OBJECTIVES To ( a ) characterize yearly changes in adherence among initially adherent patients taking statins for primary prevention and ( b ) assess the association between changes in statin adherence with subsequent risk of CV events . METHODS A 10 % r and om sample of the IMS LifeLink Health Plan Cl aims Data base covering the time period from July 1 , 1997 , to December 31 , 2008 , was used to identify a cohort of primary prevention statin users .  Adherence was estimated in yearly segments beginning with the index statin prescription using proportion of days covered ( PDC ) . PDC was categorized into 3 levels : PDC ≥ 0.80 , 0.20 ≤ PDC < 0.80 , PDC < 0.20 . Patients were excluded if they experienced CV events or had PDC < 0.80 in their first year of statin exposure . Descriptive statistics were used to explore proportions of the cohort in each PDC category during each year . Cox-proportional hazards models were used to estimate the 5-year CV event risk associated with yearly adherence transitions . RESULTS Of the 11,126 patients beginning at the highest level of adherence ( PDC ≥ 0.80 ) in year 1 , 70 % remained at this level in year 2 . Of those in this level during year 2 , 73 % remained at this level in year 3 . 828 ( 7.44 % ) experienced a CV event during their observable follow-up time . It was found that those who transitioned from the highest to the lowest level of adherence in year 2 ( PDC < 0.20 ) experienced 2.26 greater CV event hazard ( P < 0.0001 ) . Adjusting for year 2 adherence , patients at the lowest level in year 3 experienced a 271 % increase in CV hazard ( P < 0.0001 ) , as compared with the highest level of adherence . CONCLUSION This study found that  patients ' adherence levels tend to decline over time , and a transition to levels of adherence lower than a PDC of 80 % was associated with increased risk of CV events . These results are useful in the context of targeting interventions that aim to improve patients ' adherence BACKGROUND In patients with high cholesterol levels , lowering the cholesterol level reduces the risk of coronary events , but the effect of lowering cholesterol levels in the majority of patients with coronary disease , who have average levels , is less clear . METHODS In a double-blind trial lasting five years we administered either 40 mg of pravastatin per day or placebo to 4159 patients ( 3583 men and 576 women ) with myocardial infa rct ion who had plasma total cholesterol levels below 240 mg per deciliter ( mean , 209 ) and low-density lipoprotein ( LDL ) cholesterol levels of 115 to 174 mg per deciliter ( mean , 139 ) . The primary end point was a fatal coronary event or a nonfatal myocardial infa rct ion . RESULTS The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group , an absolute difference of 3 percentage points and a 24 percent reduction in risk ( 95 percent confidence interval , 9 to 36 percent ; P = 0.003 ) . Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group , a 26 percent reduction ( P=0.005 ) , and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group , a 23 percent reduction ( P=0.01 ) . The frequency of stroke was reduced by 31 percent ( P=0.03 ) . There were no significant differences in overall mortality or mortality from noncardiovascular causes . Pravastatin lowered the rate of coronary events more among women than among men . The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol . CONCLUSIONS These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels Summary The Lipid Research Clinics Coronary Primary Prevention Trial tested the efficacy of cholesterol lowering in reducing the risk of coronary heart disease in 3806 asymptomatic , middle-aged men with primary hypercholesterolaemia . The cholestyramine group experienced 8.5 and 12.6 % greater reductions in total and low density lipoprotein ( LDL ) , respectively , than those obtained in the placebo group . The cholestyramine group experienced a 19 % reduction in risk ( p < 0.05 ) of the primary end-point of definite coronary heart disease death and /or definite non-fatal myocardial infa rct ion . Corresponding and significant reductions were also seen for angina , development of a positive exercise test , and coronary bypass surgery . All-cause mortality was only slightly , and not significantly , reduced in the cholestyramine group , reflecting more violent and accidental deaths in the cholestyramine subjects . When the cholestyramine group was analysed separately , a 19 % reduction in coronary heart disease risk was also associated with each decrement of 8 % in total cholesterol . Moreover , coronary heart disease incidence in men in sustaining a fall of 25 % in total cholesterol , a typical response to the prescribed dosage ( 24 g/day ) of cholestyramine resin , was half that of men who remained at pretreatment level . The Lipid Research Clinics Coronary Primary Prevention Trial findings show that reducing total cholesterol by lowering LDL cholesterol levels , can diminish the incidence of coronary heart disease morbidity and mortality in men at high risk for the disease because of raised LDL cholesterol levels . These results have considerable importance for the prevention of coronary heart disease through cholesterol lowering , at both the clinical and public health levels PURPOSE Statin therapy has been reported to reduce the incidence of vascular events in patients with atherosclerosis , but adherence to statins may be suboptimal . The aims of this study were to quantify the rate of  statin  use among individuals with a history of coronary revascularization in a large , integrated health care system and to determine which demographic characteristics and clinical factors are associated with statin use . METHODS This was a retrospective cohort study using data base programming and chart review . The study included adult members of Kaiser Permanente Northern California with a history of coronary revascularization . The study outcome was off-statin status , defined as a ≥1-year gap between filled prescriptions . The predictor variables included age , race , body mass index , dyslipidemia , liver disease , kidney disease , and history of statin allergy . Multivariable logistic regression was used to quantify the associations between the predictor variables and statin status . A chart review of a r and omly selected subset was performed to identify reasons why individuals were not taking statins . FINDINGS The study population included 17,869 Kaiser Permanente Northern California members , of which 18.3 % had off-statin status . The following variables were associated with off-statin status : statin allergy ( odds ratio [ OR ] = 2.18 ; 95 % CI , 1.89 - 2.52 ) , end-stage renal disease ( OR = 1.55 ; 95 % CI , 1.26 - 1.91 ) , liver disease ( OR = 1.44 ; 95 % CI , 1.08 - 1.93 ) , African-American race ( OR = 1.55 vs white ; 95 % CI , 1.32 - 1.81 ) , and Latino race ( OR = 1.18 ; 95 % CI , 1.05 - 1.33 ) . The chart review found that off-statin status typically reflects patient ( 79 % ) rather than provider ( 21 % ) preference . IMPLICATION S A significant minority of patients with a history of coronary revascularization are not taking statins . Off-statin status is associated with kidney disease , liver disease , African-American race , and Latino race . At an individual level , off-statin status was usually driven by patient preference , due to minor or undefined reasons . These findings may be useful in guiding strategies to increase statin use in individuals with atherosclerosis Background Statins reduce cardiovascular morbidity and mortality after continuous treatment . Studies have shown that less than 50 % of patients take 80 % or more of prescribed doses 1 year after starting therapy . Objective To evaluate the impact of statin adherence on the incidence of coronary artery disease ( CAD ) . Methods A cohort of 115,290 patients was reconstructed using the Régie de l’assurance maladie du Québec data bases . Patients aged 45 to 85 years , without indication of cardiovascular disease ( CVD ) , and newly treated with statins between 1999 and 2004 were eligible . A nested case-control design was used to study CAD . Every case was matched for age and duration of follow-up with r and omly selected controls . The adherence level was measured by calculating the medication possession ratio . Rate ratios ( RR ) of CAD were determined through conditional logistic regression adjusted for several covariates . Results The mean patient age was 63 years , 54 % had hypertension , 26 % had diabetes , and 41 % were males . The proportion of patients with high adherence level to statins  ( ≥ 80 % ) was 74 % during the first year and 53 % after 1 year of follow-up . High adherence was associated with a risk reduction of 18 % [ RR : 0.82 ( 95 % CI : 0.77 - 0.87 ) ] compared to an adherence level of < 20 % . Developing a CVD during follow-up , being male , having been diagnosed with hypertension or diabetes , or having a high chronic disease score increased the risk of CAD . Conclusion Our study suggests that better adherence to statin agents is associated with a significant risk reduction of CAD . Adherence to statin agents needs to be improved so that patients can benefit from the full protective effects of statin therapies PURPOSE Evening administration of the conventional immediate-release ( IR ) formulation of simvastatin is recommended because of its short half-life ( 1.9 hours ) . In a healthy population , morning administration of a controlled-release ( CR ) formulation of simvastatin was shown to have equivalent lipid-lowering efficacy and a safety profile similar to that of evening doses of IR simvastatin . The present study aim ed to verify noninferiority and to compare the safety of morning administration of CR simvastatin with that of evening administration of IR simvastatin in patients with chronic kidney disease ( CKD ) who have dyslipidemia . METHODS The present study was a prospect i ve , multicenter , double-blind , Phase IV trial with an active comparator . We r and omly assigned 122 patients with CKD and dyslipidemia to 1 of 2 drug administration groups : morning administration of CR simvastatin 20 mg ( test group ) and evening administration of IR simvastatin 20 mg ( control group ) . After 8 weeks , the treatment outcomes and adverse effects of the 2 treatments were compared . FINDINGS The mean ( SD ) percentage of change in serum LDL-C at the end of treatment was -35.1 % ( 15.7 % ) for the test group and -35.6 % ( 14.6 % ) for the control group . The difference between the 2 groups was not significant ( P = 0.858 ) . The 95 % CI of the difference in the percentage of change of LDL-C between the test and control groups was -6.0 to 5.0 . There was no difference in the percentage of change of total cholesterol ( -24.3 % [ 12.5 % ] vs -26.5 % [ 12.0 % ] , P = 0.317 ) , triglyceride ( -10.6 % [ 35.1 % ] vs -12.4 % [ 33.2 % ] , P = 0.575 ) and HDL-C ( 10.2 % [ 20.7 % ] vs 4.5 % [ 11.4 % ] , P = 0.064 ) . Treatment-related adverse events were similar in both groups ( 10 events in the test group vs 8 events in the control group , P = 0.691 ) . IMPLICATION S The efficacy of morning administration of CR simvastatin was noninferior to evening administration of IR simvastatin in patients with CKD . Furthermore , the safety profile analysis showed no significant difference between the 2 treatments . Morning administration of CR simvastatin is expected to increase patient compliance and therefore better control of dyslipidemia in CKD patients 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 Summary The objective of the study was to compare compliance with and the hypocholesterolaemic effect of lovastatin given once daily as a morning or an evening dose . Twenty-four out- patients with familial hypercholesterolaemia were r and omly assigned to receive placebo first , then lovastatin 20 mg , to be taken once daily for 4 weeks , either with the breakfast or evening meal , in a single-blind fashion . Drug compliance was assessed by pill counts and continuous electronic monitoring . Two compliance parameters were evaluated , consumption , defined as percentage of prescribed doses taken , and time compliance , the percentage of total dosing events recorded within defined intervals ( 6.00–10.00 h , and 17.00–21.00 h ) , for the morning and evening regimes . Both regimes satisfactorily reduced the total and LDL-cholesterol concentrations , and there was no significant difference in the extent of the reductions . Pill counts overestimated compliance , as revealed by the monitoring method . The times of actual consumption of doses by the patients often differed from that prescribed , predominantly in patients who were told to take the evening dose . Partial time compliance may have confounded the efficacy of the drugs . Electronic compliance monitoring appears to be particularly useful in chronopharmacological studies Abstract Risk of coronary heart disease over 14 years was examined prospect ively in 2,282 men and 2,845 women according to their antecedent cholesterol and lipoprotein status . An increased risk pro This was an open‐label , r and omized , three‐period , three‐treatment , multiple dose , crossover study in 12 healthy male and female subjects . This study evaluated single dose and steady‐state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet , Lescol ® XL 80 mg and 160 mg doses once a day . The study also included a twice a day administration of an immediate release ( IR ) form of fluvastatin capsule , Lescol ® , for comparative purpose s. All doses were administered for 7 days . The safety and tolerability were also assessed . The pharmacokinetics of fluvastatin  were evaluated on days 1 and 7 following each treatment . Fluvastatin systemic exposure was 50 % less when administered as Lescol ® XL 80 mg qd compared with Lescol ® IR 40 mg bid . Conversely , fluvastatin systemic exposure was 22 % higher when administered as Lescol ® XL 160 mg qd compared with Lescol ® IR 40 mg bid . Single doses of Lescol ® XL 80 mg and 160 mg were dose proportional but , deviation ( 30 % ) from dose proportionality was observed for the Lescol ® XL 160 mg at steady‐state . There appeared to be moderate ( 20%–40 % ) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol ® XL tablets . Both Lescol ® XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half‐life compared with fluvastatin IR capsule . Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population .  Adverse event profiles were consistent with the published safety profile of the marketed formulations . Aside from one incidence of creatine phosphokinase ( CPK ) elevation ( following Lescol ® XL 160 mg qd treatment ) , there were no safety concerns with any of the treatments when administered acutely ( 7 days ) . Copyright © 2004 John Wiley & Sons , BACKGROUND The beneficial effects of statins on cardiovascular mortality in secondary prevention have been established in several long-term , placebo-controlled trials . However , the value of statin therapy in reduction of overall mortality in patients without coronary heart disease ( CHD ) is question able . This study evaluated the effect of statin therapy in subjects with no indication of cardiovascular disease ( primary prevention ) and patients with known CHD ( secondary prevention ) . METHODS This retrospective cohort study included 229 918 adult enrollees in a health maintenance organization in Israel who initiated statin treatment from 1998 through 2006 ( mean age , 57.6 years ; 50.8 % female ) .  Proportion of days covered ( PDC ) with  statins  was measured by the number of dispensed  statin prescriptions during the interval between the date of the first statin prescription and the end of follow-up . RESULTS During a mean of 4.0 and 5.0 years of follow-up , there were 4259 and 8906 deaths among the primary prevention and secondary prevention cohorts , respectively . In both cohorts , continuity of treatment with statins ( PDC , > or = 90 % ) conferred at least a 45 % reduction in risk of death compared with patients with a PDC of less than 10 % . A stronger risk reduction was calculated among patients with high baseline low-density lipoprotein cholesterol level and patients initially treated with high-efficacy statins . CONCLUSIONS Better continuity of statin treatment provided an ongoing reduction in mortality among patients with and without a known history of CHD . The observed benefits from statins were greater than expected from r and omized clinical trials Although the beneficial effect of statins in secondary prevention of cardiac events is well established , their effectiveness in primary prevention is question able when most evidence derives from r and omized controlled trials and not " real-life " data . To evaluate the association between persistent use of statins and risk of acute nonfatal cardiovascular events  in primary prevention patients in community setting s , we retrospectively analyzed a cohort of 171,535 adults 45 to 75 years old with no indication of cardiovascular disease who began statin therapy from 1998 to 2009 in a large health maintenance organization in Israel . Persistence with statins was measured by the proportion of days covered with dispensed prescriptions of statins during the follow-up period . Main outcome measurements were occurrence of myocardial infa rct ion or performance of a cardiac revascularization procedure . Incidence of acute cardiovascular events during the follow-up period ( 993,519 person-years ) was 10.22 per 1,000 person-years . Persistence with statins was associated with a lower risk of incident cardiac events ( p for trend < 0.01 ) . The most persistent users ( covered with statins for ≥80 % of their follow-up time ) had a hazard ratio of 0.58 ( 95 % confidence interval 0.55 to 0.62 ) compared to nonpersistent users ( proportion of days covered < 20 % ) . Similar results were found when analyses were limited to patients with > 5 years of follow-up . Treatment with high efficacy statins was associated with a lower risk of cardiac events . In conclusion , our large and unselected community-based study supports the results of r and omized controlled trials regarding the beneficial effect of statins in the primary prevention of acute cardiac events 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 Objective : To test whether the time of administration influences the therapeutic response to a calcium antagonist taken once a day . Also , the dynamics of drug compliance and its impact on blood pressure control were investigated Design : Twenty out patients with mild-to-moderate hypertension were included in a r and omized , placebo-controlled open study . In a crossover design , all of the patients received 5 mg amlodipine , either in the morning or in the evening , during two consecutive 4-week treatment periods Methods : Blood pressure was taken by casual measurement , ambulatory 24-h monitoring ( SpaceLabs 90202 ) and self-measurement at home , performed with a semi-automatic oscillometric device during the whole study period . Compliance was assessed using the Medication-Event-Monitoring System ( MEMS ) Results : Neither casual nor ambulatory day- or night-time readings detected a significant difference between morning and evening administration . However , self-measurement documented significantly greater blood pressure reductions for morning than for evening administration . The MEMS showed different compliance on the days of ambulatory monitoring ( 100 % with both drug regimens ) compared with the whole treatment period . The number of days with missed medication was thus significantly higher for the evening dosing regimen . The difference in self-measured blood pressure between the two regimens was lost if the days with missed medication were removed from the statistical analysis Conclusions : Time of once-a-day amlodipine administration does not influence its efficacy for 24-h blood pressure control . Furthermore , the use of self-measurement and the MEMS may provide useful additional information on the pharmacodynamic impact of different dosing patterns in hypertensive AIMS Cardiovascular polypills are a novel strategy in the prevention of cardiovascular disease . Based on considerations about the effectiveness , the individual pills of a polypill are taken at different times of the day . This study aim ed therefore to compare the use of a polypill in the morning , in the evening or the individual components taken at their usual times on cardiovascular risk factors and patient acceptability . METHODS The study was a r and omized three-period crossover trial . Seventy-eight patients with established cardiovascular disease were r and omly allocated to the use of polypill ( aspirin 75 mg , simvastatin 40 mg , lisinopril 10 mg and hydrochlorothiazide 12.5 mg ) in the morning , in the evening or use of the individual agents taken at different time points ( Trial : NCT01506505 ) . RESULTS Using the polypill in the evening result ed in a 0.2 mmol/L ( 95%-confidence interval ( CI ) : 0.1 to 0.3 ) lower fasting LDL-cholesterol compared to the use in the morning , and not statistically significantly different mean 24-hour systolic BP ( mean difference : 0.7 mmHg ; 95%-CI ; -2.1 to 3.4 ) . Compared to the use of the individual agents , the mean LDL-cholesterol was 0.2 mmol/L ( 95%-CI : 0.1 to 0.3 ) higher when using the polypill in the morning , but not statistically significantly different when used in the evening ( mean difference : -0.1 mmol/L ; 95%-CI : -0.1 to 0.0 ) . Furthermore , there were no differences in mean 24-hour systolic BP with morning use ( mean difference : 0.4 mmHg ; 95%-CI ; -1.5 to 2.3 ) or evening use ( mean difference : 1.0mmHg ; 95%-CI ; -0.8 to 2.8 ) of the polypill compared to the individual agents . The adherence was 5.2 % ( 95%-CI : 1.4 to 9.1 ) higher with morning use of the polypill and 5.0 % ( 95%-CI : 1.5 to 8.5 ) higher with evening use compared to the individual agents . Treatment with the polypill was preferred by 92 % of the participants . CONCLUSION The use of a polypill in the evening was more effective in lowering LDL-cholesterol , and result ed in not statistically significantly different ambulatory BP levels compared to the use of a polypill in the morning . Therapy with a polypill was associated with an increased adherence . The polypill is highly preferred by patients , demonstrating a potential role for the polypill in the prevention of cardiovascular disease PURPOSE The effects of morning versus evening administration of atorvastatin in hyperlipidemic patients were studied . METHODS Patients whose care was managed by a teaching hospital run by the Department of Veterans Affairs who were prescribed atorvastatin calcium 40 mg p.o . daily by their primary care physician were interviewed by a clinical pharmacist in the ambulatory care clinic for study enrollment . Patients were excluded if they had diseases or conditions or took medication known to affect serum lipoprotein levels , as were patients who consumed more than three alcoholic drinks per day and those who could not verify the time of atorvastatin administration . Blood sample s were collected after a 12-hour fasting period and serum lipoprotein levels were measured at baseline and after four weeks . RESULTS Of the 204 hyperlipidemic patients receiving atorvastatin , 64 met the inclusion criteria and were enrolled in the study , 32 of whom took the drug in the morning ( before noon ) and an equal number who took the drug at night ( after 6 p.m. but before midnight ) . All patients were male out patients with a mean + /- S.D. age of 57.8 + /- 7.8 years and 58.5 + /- 7.8 years for the morning and evening administration groups , respectively . No statistically significant differences in lipid values measured were found between the morning and evening administration group after four weeks . CONCLUSION Changes in the levels of total cholesterol , low-density-lipoprotein cholesterol , triglycerides , and high-density-lipoprotein cholesterol were similar among hyperlipidemic patients receiving atorvastatin calcium 40 mg , regardless of the time of day the drug was administered This 8-week multicenter , placebo-controlled trial compared the efficacy and safety of the HMG-CoA reductase inhibitor , pravastatin , when administered either as single doses of 40 mg in the morning ( AM ) or evening ( PM ) or 20 mg twice daily ( bid ) in 196 diet-stabilized out patients with primary type II hypercholesterolemia . Mean reductions in total and low-density lipoprotein ( LDL ) cholesterol concentrations were observed in all pravastatin groups after 1 week and were sustained throughout the study ( P less than or equal to 0.001 versus baseline and placebo ) . At week 8 , mean reductions from baseline in the pravastatin treatment groups were 23 - 27 % for total cholesterol and 30 - 34 % for LDL cholesterol . LDL cholesterol was reduced greater than or equal to 15 % by pravastatin in all patients in the group treated with 40 mg PM and in 88 and 96 % in those receiving 20 mg bid and 40 mg AM , respectively . High density lipoprotein cholesterol was elevated ( up to 8 % ) and triglycerides were reduced ( up to 25 % ) by all pravastatin regimens ( P less than or equal to 0.05 ) . Pravastatin was well tolerated and was associated with a low incidence of adverse events . No patient withdrew from the study due to a pravastatin-related  adverse event . Once-daily pravastatin is a safe and effective treatment for patients with primary hypercholesterolemia and has a favorable safety profile 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 The Sc and inavian Simvastatin Survival Study ( 4S ) r and omized 4444 patients with coronary heart disease ( CHD ) and serum cholesterol 5.5 to 8.0 mmol/L ( 213 to 310 mg/dL ) with triglycerides < or = 2.5 mmol/L ( 220 mg/dL ) to simvastatin 20 to 40 mg or placebo once daily . Over the median follow-up period of 5.4 years , one or more major coronary events ( MCEs ) occurred in 622 ( 28 % ) of the 2223 patients in the placebo group and 431 ( 19 % ) of the 2221 patients in the simvastatin group ( 34 % risk reduction , P<.00001 ) . Simvastatin produced substantial changes in several lipoprotein components , which we have attempted to relate to the beneficial effects observed . METHODS AND RESULTS The Cox proportional hazards model was used to assess the relationship between lipid values ( baseline , year 1 , and percent change from baseline at year 1 ) and MCEs . The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol , apolipoprotein B , and less so with HDL cholesterol , but there was no clear relationship with triglycerides . We estimate that each additional 1 % reduction in LDL cholesterol reduces MCE risk by 1.7 % ( 95 % CI , 1.0 % to 2.4 % ; P<.00001 ) . CONCLUSIONS These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol , and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients
target: 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: 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 .