The Evening versus Morning Polypill Utilization Study: the TEMPUS rationale and design Effect of morning versus evening intake of simvastatin on the serum cholesterol level in patients with coronary artery disease. Effects of morning versus evening administration of atorvastatin in patients with hyperlipidemia. Comparison of Effects of Morning Versus Evening Administration of Ezetimibe/Simvastatin on Serum Cholesterol in Patients with Primary Hypercholesterolemia Taking simvastatin in the morning compared with in the evening: randomised controlled trial 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. Time-of-intake (morning versus evening) of extended-release fluvastatin in hyperlipemic patients is without influence on the pharmacodynamics (mevalonic acid excretion) and pharmacokinetics. Lipid lowering efficacy between morning and evening simvastatin treatment: a randomized double-blind study. Efficacy and Safety of Fluvastatin-Extended Release in Hypercholesterolemic Patients: Morning Administration Is Equivalent to Evening Administration Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening. 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. Is there a BP benefit of changing the time of aspirin administration in treated hypertensive patients? Pharmacodynamic effects and pharmacokinetics of a new HMG-CoA reductase inhibitor, rosuvastatin, after morning or evening administration in healthy volunteers. Early intensive statin treatment for six months improves long-term clinical outcomes in patients with acute coronary syndrome (Extended-ESTABLISH trial): a follow-up study. 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. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. Effect of dosing time of angiotensin II receptor blockade titrated by self-measured blood pressure recordings on cardiorenal protection in hypertensives: the Japan Morning Surge-Target Organ Protection (J-TOP) study
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 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 ) 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 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 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 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 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 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 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 The pharmacodynamic effects and pharmacokinetics of atorvastatin , a potent investigational inhibitor of HMG-CoA reductase , were studied in 16 normolipidemic subjects after administration of 40 mg daily for 15 days in the morning or evening .  Lipid and apolipoprotein parameters were determined , and plasma atorvastatin equivalent concentrations were measured according to a vali date d enzyme inhibition bioassay procedure . Atorvastatin was well tolerated by the participants . Overall , mean reductions of 34 % in total cholesterol , 48 % in low-density lipoprotein ( LDL ) cholesterol , 37 % in very low density lipoprotein ( VLDL ) cholesterol , 25 % in triglycerides , 6 % in apolipoprotein A-I , and 34 % in apolipoprotein B were observed . Changes in lipid and apolipoprotein values were similar after morning and evening administration of atorvastatin . In contrast , studies with other HMG-CoA reductase inhibitors have consistently shown that evening administration results in larger reductions in total and LDL cholesterol than does morning administration . Rate and extent of equivalent absorption of atorvastatin  were lower during evening than morning administration . Mean elimination half-life values were similar , however , suggesting that there is no diurnal variation in disposition of this drug . Pharmacokinetic differences did not correlate with effects on serum lipids 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 Background and design : The effects of aspirin on blood pressure ( BP ) are controversial and a chronopharmacological effect of aspirin on 24-hour BP was reported recently in otherwise untreated hypertensive patients . The study was design ed to test the timing effect of aspirin dosing on 24-hour BP in treated hypertensive patients routinely taking aspirin for cardiovascular prevention . Method and results : Seventy-five patients were r and omized into two groups . One group was to receive aspirin in the evening then in the morning for 1 month and the other group in the morning then in the evening , following a cross-over design . The principal assessment criterion was 24-hour systolic BP ( SBP ) measured by 24-hour ambulatory BP monitoring ( ABPM ) . Patients were aged 65 ± 9 years and had been hypertensive for 12 ± 10 years . They were all taking a mean of 2.8 antihypertensive drugs and did not modify their treatment throughout the study . Of the included subjects , 70 % were men and 33 % were diabetics . Mean 24-hour SBP values were clinical ly equivalent and were not statistically different , depending on whether the aspirin was taking in the morning or evening ( 128.3 ± 1.4 vs. 128.3 ± 1.4 mmHg , respectively ) . Neither was there any significant difference in diurnal and nocturnal SBP or in 24-hour , diurnal , and nocturnal diastolic BP ( DBP ) . Conclusion : It does not appear useful to advise patients with long-st and ing hypertension to modify timing of aspirin intake in order to reduce BP values 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 BACKGROUND The ESTABLISH trial found using volumetric intravascular ultrasound that atorvastatin therapy started early and continued for 6 months significantly reduced plaque volume in patients with acute coronary syndrome ( ACS ) . However , the benefits of early statin administration on long-term outcomes remain unclear . We therefore examined whether the early initiation of statin in patients with ACS improves long-term prognosis . METHODS AND RESULTS The Extended-ESTABLISH trial included 180 patients with ACS who underwent emergency percutaneous coronary intervention ( PCI ) . These patients were r and omized here to groups given either early intensive lipid-lowering therapy ( n=90 ; atorvastatin 20 mg/day ) or st and ard care ( control , n=90 ) within 48 h of events . Baseline characteristics between the two groups did not significantly differ at the time of ACS onset . Six months after PCI , all patients were treated with statins to achieve an LDL-C value of < 100 mg/dL. We compared the first occurrence of major adverse cardiac and cerebrovascular events ( MACCE ) . Prognostic data were fully documented during the entire follow-up period ( mean , 1538+/-707 days ) . Cumulative event-free survival was significantly higher in the atorvastatin , than in the control group ( p=0.041 ; log-rank test ) . Furthermore , by adjusting for vali date d prognosticators , early statin administration was identified as a good predictor of MACCE ( HR 0.46 , 95%CI 0.23 - 0.86 ; p=0.015 ) . CONCLUSIONS In-hospital initiation of statin therapy immediately after ACS conferred long-term benefits and 6 months of intensive lipid-lowering therapy improved long-term clinical outcomes after PCI in patients with ACS 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 BACKGROUND Lipid-lowering therapy with statins reduces the risk of cardiovascular events , but the optimal level of low-density lipoprotein ( LDL ) cholesterol is unclear . METHODS We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40  mg of pravastatin daily ( st and ard therapy ) with 80 mg of atorvastatin daily ( intensive therapy ) . The primary end point was a composite of death from any cause , myocardial infa rct ion , documented unstable angina requiring rehospitalization , revascularization ( performed at least 30 days after r and omization ) , and stroke . The study was design ed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event . Follow-up lasted 18 to 36 months ( mean , 24 ) . RESULTS The median LDL cholesterol level achieved during treatment was 95 mg per deciliter ( 2.46 mmol per liter ) in the st and ard-dose pravastatin group and 62 mg per deciliter ( 1.60 mmol per liter ) in the high-dose atorvastatin group ( P<0.001 ) . Kaplan-Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group , reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin ( P=0.005 ; 95 percent confidence interval , 5 to 26 percent ) . The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen . CONCLUSIONS Among patients who have recently had an acute coronary syndrome , an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a st and ard regimen . These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels Objectives To study the impact of the dosing time of an angiotensin II receptor blocker ( ARB ) titrated by self-measured home blood pressure ( HBP ) on cardiorenal damage in hypertensives . Methods We conducted an open-label multicenter trial , the J-TOP study , that enrolled 450 hypertensives with self-measured systolic HBP more than 135 mmHg . The study patients were stratified into three groups according to the difference between their morning and evening SBPs difference : a morning hypertension group ( morning and evening difference at least 15 mmHg ; n = 170 ) , a morning and evening hypertension group ( 0 mmHg ≤ morning and evening difference < 15 mmHg ; n = 198 ) , and an evening hypertension group ( morning and evening difference < 0 mmHg ; n = 82 ) . Individuals were then r and omly allocated to receive bedtime dosing or awakening dosing of c and esartan ( ± diuretic as needed ) titrated to achieve a target systolic HBP less than 135 mmHg . The 6-month change in the urinary albumin/creatinine ratio ( UACR ) was assessed . Results In total patients , the UACR was more markedly reduced in the bedtime-dosing group than in the awakening-dosing group ( −45.7 vs. −34.5 % , P = 0.02 ) , whereas there were no differences in the reduction of any of the HBPs including the sleep blood pressures ( BPs ) between the two groups . Among the three subgroups stratified by the morning and evening difference , the difference in the UACR reduction between the bedtime-dosing and awakening-dosing groups was only significant in the morning hypertension group ( −50.6 vs. −31.3 % , P = 0.02 ) . Conclusion In HBP-guided antihypertensive treatment in hypertensives , bedtime dosing of an ARB may be superior to awakening dosing for reducing microalbuminuria
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 .