***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The effects of demographic and clinical covariates on the apparent clearance ( CL/F ) of orally administered atorvastatin , with chronic dosing in a patient population that included the elderly , were studied in 143 patients ( atorvastatin : 34 ± 26 mg/day , mean ± SD ; men ( n = 64 ) , age 64.6 ± 12.1 years , and women ( n = 79 ) , age 69.3 ± 13 years ) . The time of dose administration had a strong influence on Ka ( faster with morning dosing ) ; the factors found to slow CL/F were coadministration of CYP3A inhibitors and advancing age — the latter factor was relevant only in the men , not in the women The effect of HMG‐CoA reductase inhibitors on Lp(a ) concentrations is controversial , with some studies showing an increase and others showing no effect on Lp(a ) concentrations . Many of these studies have been limited by small sample size and the lack of a prospect i ve design . We evaluated the effect of four treatments : ( 1 ) placebo , ( 2 ) simvastatin 10 mg PO QPM , ( 3 ) simvastatin 20 mg PO QAM , and ( 4 ) simvastatin 20 mg PO QPM on Lp(a ) concentrations in a prospect i ve , r and omized , controlled clinical trial of 24 weeks in 343 subjects in 28 clinical sites in the United States .  Simvastatin was not associated with a change in Lp(a ) concentrations relative to placebo . These results were not affected by controlling for race , initial Lp(a ) level , or urinary albumin excretion  . Simvastatin significantly reduced low‐density lipoprotein ( LDL ) cholesterol levels ( 10 mg PO QPM : ‐ 27.6 % ; 20 mg PO QAM : ‐ 28.1 % ; and 20 mg PO QPM : ‐ 34.3 % , all p<0.001 ) . It was concluded that in a large , r and omized , controlled trial , simvastatin does not affect Lp(a ) levels but markedly lowers LDL cholesterol levels 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 ) 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 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 CONTEXT Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease ( CHD ) , it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol ( LDL-C ) in patients without CHD extends to individuals with average serum cholesterol levels , women , and older persons . OBJECTIVE To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinical ly evident atherosclerotic cardiovascular disease with average total cholesterol ( TC ) and LDL-C levels and below-average high-density lipoprotein cholesterol ( HDL-C ) levels . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING Outpatient clinics in Texas . PARTICIPANTS A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C ( as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [ NHANES ] III ) . Mean ( SD ) TC level was 5.71 ( 0.54 ) mmol/L ( 221 [ 21 ] mg/dL ) ( 51 st percentile ) , mean ( SD ) LDL-C level was 3.89 ( 0.43 ) mmol/L ( 150 [ 17 ] mg/dL ) ( 60th percentile ) , mean ( SD ) HDL-C level was 0.94 ( 0.14 ) mmol/L ( 36 [ 5 ] mg/dL ) for men and 1.03 ( 0.14 ) mmol/L ( 40 [ 5 ] mg/dL ) for women ( 25th and 16th percentiles , respectively ) , and median ( SD ) triglyceride levels were 1.78 ( 0.86 ) mmol/L ( 158 [ 76 ] mg/dL ) ( 63rd percentile ) . INTERVENTION Lovastatin ( 20 - 40 mg daily ) or placebo in addition to a low-saturated fat , low-cholesterol diet . MAIN OUTCOME MEASURES First acute major coronary event defined as fatal or nonfatal myocardial infa rct ion , unstable angina , or sudden cardiac death . RESULTS After an average follow-up of 5.2 years , lovastatin reduced the incidence of first acute major coronary events ( 1 83 vs 116 first events ; relative risk [ RR ] , 0.63 ; 95 % confidence interval [ CI ] , 0.50 - 0.79 ; P<.001 ) , myocardial infa rct ion ( 95 vs 57 myocardial infa rct ions ; RR , 0.60 ; 95 % CI , 0.43 - 0.83 ; P=.002 ) , unstable angina ( 87 vs 60 first unstable angina events ; RR , 0.68 ; 95 % CI , 0.49 - 0.95 ; P=.02 ) , coronary revascularization procedures ( 157 vs 106 procedures ; RR , 0.67 ; 95 % CI , 0.52 - 0.85 ; P=.001 ) , coronary events ( 215 vs 163 coronary events ; RR , 0.75 ; 95 % CI , 0.61 - 0.92 ; P = .006 ) , and cardiovascular events ( 255 vs 194 cardiovascular events ; RR , 0.75 ; 95 % CI , 0.62 - 0.91 ; P = .003 ) . Lovastatin ( 20 - 40 mg daily ) reduced LDL-C by 25 % to 2.96 mmol/L ( 115 mg/dL ) and increased HDL-C by 6 % to 1.02 mmol/L ( 39 mg/dL ) . There were no clinical ly relevant differences in safety parameters between treatment groups . CONCLUSIONS Lovastatin reduces the risk for the first acute major coronary event  in men and women with average TC and LDL-C levels and below-average HDL-C levels . These findings support the inclusion of HDL-C in risk-factor assessment , confirm the benefit of LDL-C reduction to a target goal , and suggest the need for re assessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention BACKGROUND Fluvastatin sodium is a new , entirely synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that may be an effective lipid-lowering agent in patients whose hyperlipidemia does not respond to dietary therapy . We conducted a study to evaluate the effects of fluvastatin on lipop 
    Output:
    
Limited and low- quality evidence suggested that there were no differences between chronomodulated treatment with statins in people with hyperlipidaemia as compared to conventional treatment with statins , in terms of clinical ly relevant outcomes .
The review did not find differences in adverse events associated with statins between both regimens .
Taking statins in the evening does not have an effect on the improvement of lipid levels with respect to morning administration .