Covariate adjustment increased power in randomized controlled trials: an example in traumatic brain injury. Larger effect sizes were associated with higher quality ratings in complementary and alternative medicine randomized controlled trials. The effect of statin therapy on ventricular late potentials in acute myocardial infarction. Aldosterone and cortisol predict medium-term left ventricular remodelling following myocardial infarction. On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). A simplified search strategy for identifying randomised controlled trials for systematic reviews of health care interventions: a comparison with more exhaustive strategies Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study. Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin  Statins and Exercise Training Response in Heart Failure Patients: Insights From HF-ACTION. Deterioration of glucose homeostasis in type 2 diabetic patients one year after beginning of statins therapy. Effects of Rosuvastatin With or Without Ezetimibe on Clinical Outcomes in Patients Undergoing Elective Vascular Surgery Physiological-dose steroid therapy in sepsis [ISRCTN36253388] Adding exercise to rosuvastatin treatment: influence on C-reactive protein, monocyte toll-like receptor 4 expression, and inflammatory monocyte (CD14+CD16+) population. Are Observational Studies More Informative Than Randomized Controlled Trials in Hypertension?: Con Side of the Argument [Effect of various approaches to therapy with statins in high risk patients from the point of view of vascular endothelium]. Treating to target patients with primary hyperlipidaemia:comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study)
OBJECTIVE We aim ed to determine to what extent covariate adjustment could affect power in a r and omized controlled trial ( RCT ) of a heterogeneous population with traumatic brain injury ( TBI ) . STUDY DESIGN AND SETTING We analyzed 14-day mortality in 9,497 participants in the Corticosteroid R and omization After Significant Head Injury ( CRASH ) RCT of corticosteroid vs. placebo . Adjustment was made using logistic regression for baseline covariates of two vali date d risk models derived from external data ( International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury [ IMPACT ] ) and from the CRASH data . The relative sample size ( RESS ) measure , defined as the ratio of the sample size required by an adjusted analysis to attain the same power as the unadjusted reference analysis , was used to assess the impact of adjustment . RESULTS Corticosteroid was associated with higher mortality compared with placebo ( odds ratio=1.25 , 95 % confidence interval=1.13 - 1.39 ) . RESS of 0.79 and 0.73 were obtained by adjustment using the IMPACT and CRASH models , respectively , which , for example , implies an increase from 80 % to 88 % and 91 % power , respectively . CONCLUSION Moderate gains in power may be obtained using covariate adjustment from logistic regression in heterogeneous conditions such as TBI . Although analyses of RCTs might consider covariate adjustment to improve power , we caution against this approach in the planning of RCTs OBJECTIVE To determine if the quality of  complementary and alternative medicine ( CAM ) placebo controlled r and omized controlled trials ( RCTs ) is related to the effect sizes they produce when the type of interventions and outcome variables are controlled . STUDY DESIGN AND SETTING A sample of 25 CAM meta-analyses was identified from MEDLINE and h and search es containing published effect sizes for at least three efficacy trials employing placebo control groups .  From these 25 review s , 26 pairs of trials were selected : the one reporting the largest effect size and the matching trial reporting the smallest effect size . Quality and publication characteristics were then abstract ed from each trial . RESULTS Unlike the preponderance of past evidence examining the relationship between quality and effect size , the present study found that trials possessing the largest effect sizes within a meta- analysis were also associated with higher quality ratings than their counterparts possessing the lowest effect sizes ( P=.019 ) . CONCLUSIONS Possible theoretical reasons for this unexpected positive relationship include ( a ) sampling error , ( b ) reduced within group variation , ( c ) fraudulent reporting , and ( d ) the restriction of the analyses to placebo controlled trial AIMS To determine whether early statin therapy in acute myocardial infa rct ion has any effect on ventricular late potentials which are considered as a noninvasive tool for evaluation of arrhythmogenic substrate . METHODS AND RESULTS Study population consisted of prospect ively enrolled 72 patients presenting with acute myocardial infa rct ion ( < 6 h ) . Thirty-four of the patients were r and omized to pravastatin ( 40 mg/day ) on admission irrespective of lipid levels . All patients received thrombolytic therapy .  Signal-averaged ECG recordings were obtained serially prior to thrombolytic therapy , 48 h after and 10 days later . Late potentials were defined as positive if signal-averaged ECG met at least two of Gomes criteria : filtered total QRS duration > 114 ms , root mean square voltage of the last 40 ms of the QRS < 20 mV , or the duration of the terminal low ( < 40 mV ) amplitude signals > 38 ms . Changes observed in signal-averaged ECG recordings after thrombolysis were evaluated statistically with regard to statin usage . There were no significant differences between the clinical characteristics of the two r and omized groups . There was a significant decrease in the rates of late potentials between the first and third signal-averaged ECG recordings after thrombolytic therapy in pravastatin group . Pravastatin group also had lower incidence of ventricular arrhythmias compared with control group ( 26 vs. 63 % , P=0.021 ) . The in-hospital cardiovascular event rates were also lower in statin group . CONCLUSION Early use of pravastatin reduces the incidence of late potentials following thrombolytic therapy in acute myocardial infa rct ion . Statin therapy also seems to be reducing the incidence of in-hospital ventricular arrhythmias . These beneficial effects of statins might be explained through prevention of new myocardial ischemic episodes due to early plaque stabilization or regulation of endothelial and platelet functions AIMS Mineralocorticoid receptor ( MR ) antagonists improve cardiovascular outcomes in patients with heart failure complicating acute myocardial infa rct ion ( AMI ) and in chronic heart failure . It is unclear whether these beneficial effects are due solely to aldosterone blockade , as MR has a similar affinity for cortisol . We examined the relationships between plasma and urinary steroid hormones and left ventricular ( LV ) remodelling in patients with LV dysfunction following AMI . METHODS AND RESULTS Plasma concentrations of renin , aldosterone , and N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , and 24 h urinary excretion rates of tetrahydroaldosterone ( THAldo ) and total cortisol metabolites were measured in 93 patients at a mean of 46 h following AMI prior to contrast-enhanced cardiac magnetic resonance ( ceCMR ) .  Patients were then r and omized to 24 weeks of placebo or eplerenone therapy in addition to st and ard treatment , after which ceCMR was repeated . In placebo-treated patients , aldosterone , NT-proBNP , and excretion rates of THAldo and total cortisol metabolites were univariate predictors of remodelling ( i.e. change in LV end-systolic volume index ) ; aldosterone ( P = 0.040 ) and total cortisol metabolite excretion ( P = 0.038 ) remained independent predictors on multivariate analysis . None of the measured biomarkers predicted remodelling in the presence of eplerenone . Plasma and urinary aldosterone measures , and urinary cortisol metabolites , were not only related to larger infa rct volumes and greater infa rct remodelling over time , but were also higher in patients with microvascular obstruction on baseline ceCMR . CONCLUSION Aldosterone and cortisol are associated with medium-term LV remodelling when measured early after AMI . The beneficial effects of MR antagonism may relate to blockade of both aldosterone- and cortisol-induced MR activation BACKGROUND We aim ed to determine the efficacy and safety of adding ezetimibe ( Ez ) to simvastatin ( S ) in a post-acute coronary syndrome ( ACS ) population in a prespecified on-treatment analysis . METHODS We evaluated 17,706 post-ACS patients from the IMPROVE-IT trial who had low-density lipoprotein cholesterol values between 50 and 125 mg/dL and who received Ez 10 mg/d with S 40 mg/d ( Ez/S ) or placebo with simvastatin 40 mg/d ( P/S ) . The primary composite end point was cardiovascular death , myocardial infa rct ion , unstable angina , coronary revascularization ≥30 days postr and omization , or stroke . The on-treatment analysis included patients who received study drug for the duration of the trial or experienced a primary end point or noncardiovascular death within 30 days of drug discontinuation . RESULTS Mean low-density lipoprotein cholesterol values at 1 year were 71 mg/dL for P/S and 54 mg/dL for Ez/S ( absolute difference -17 mg/dL = -24 % ; P < .001 ) . The 7-year Kaplan-Meier estimate of the primary end point occurred in 32.4 % in the P/S arm and 29.8 % in the Ez/S arm ( absolute difference 2.6 % ; HRadj 0.92 [ 95 % CI 0.87 - 0.98 ] ; P = .01 ) . The absolute treatment effect favoring Ez/S was 30 % greater than in the intention-to-treat analysis of IMPROVE-IT . CONCLUSIONS This analysis provides additional support for the efficacy and safety of adding Ez to S in this high-risk , post-ACS population Background It is generally believed that exhaustive search es of bibliographic data bases are needed for systematic review s of health care interventions . The CENTRAL data base of controlled trials ( RCTs ) has been built up by exhaustive search ing . The CONSORT statement aims to encourage better reporting , and hence indexing , of RCTs . Our aim was to assess whether developments in the CENTRAL data base , and the CONSORT statement , mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic review s of health care interventions . Methods RCTs used in the Cochrane review s were identified . A brief RCT search strategy ( BRSS ) , consisting of a search of CENTRAL , and then for variants of the word r and om across all fields ( r and om$.af . ) in MEDLINE and EMBASE , was devised and run . Any trials included in the meta-analyses , but missed by the BRSS , were identified . The meta-analyses were then re-run , with and without the missed RCTs , and the differences quantified . The proportion of trials with variants of the word r and om in the title or abstract was calculated for each year . The number of RCTs retrieved by search ing with " r and om$.af . " was compared to the highly sensitive search strategy ( HSSS ) . Results The BRSS had a sensitivity of 94 % . It found all journal RCTs in 47 of the 57 review s. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five review s , but no important differences in conclusions result ed . In the post-CONSORT years , 1997–2003 , the percentage of RCTs with r and om in the title or abstract was 85 % , a mean increase of 17 % compared to the seven years pre-CONSORT ( 95 % CI , 8.3 % to 25.9 % ) . The search using r and om$.af . reduced the MEDLINE retrieval by 84 % , compared to the HSSS , thereby reducing the workload of checking retrievals . Conclusion A brief RCT search strategy is now sufficient to locate RCTs for systematic review s in most cases . Exhaustive search ing is no longer cost-effective , because in effect it has already been done for CENTRAL OBJECTIVE Evaluate the lipid-altering effects of ezetimibe added to ongoing statin therapy , statin titration , switching from statin monotherapy to a more potent statin or to ezetimibe/simvastatin . METHODS A pooled analysis of patient-level data from 17 double-blind , active or placebo-controlled studies of 8667 hypercholesterolemic adults r and omized to  ezetimibe 10 mg added to ongoing statins , statin titration ( doubling ) , or switching from ongoing statins to rosuvastatin ( 10 mg ) or to ezetimibe/simvastatin ( 10/20 and 40 mg ) . Percent change from baseline in low-density lipoprotein cholesterol ( LDL-C ) was estimated by analysis of variance . Percent of patients who achieved LDL-C and other guideline -recommended targets , and target lipid levels by baseline distance to goal were evaluated . RESULTS LDL-C percent change from baseline was -26.0 for ezetimibe added to ongoing statin therapy , -27.6 for switching from ongoing statin to ezetimibe/simvastatin , -19.7 for switching to rosuvastatin 10 mg , and -9.7 for dose doubling of the ongoing statin . For patients within 0.8 mmol/L ( 30 mg/dL ) of the target at baseline , LDL-C target attainment rates were 75.9 % for adding ezetimibe to ongoing statin , 72.8 % for switching to ezetimibe/simvastatin , 61.8 % for switching to rosuvastatin , and 44.3 % for statin dose-doubling . Similarly , improvements in other lipids and achievement of non-high-density lipoprotein cholesterol and apolipoprotein B targets among this patient group were largest for ezetimibe added to ongoing statins and switching to ezetimibe/simvastatin ; switching to rosuvastatin 10 mg and statin dose-doubling were less effective . CONCLUSIONS Adding ezetimibe to ongoing statin therapy appeared to be an effective option for patients who do not achieve lipid-lowering goals on statins alone BACKGROUND Statins improve cardiovascular outcome , but less is known on the renal outcome . We , therefore , studied the relationship between the use of statins and urinary albumin excretion ( UAE ) and glomerular filtration rate ( GFR ) in two setting s : a r and omized controlled trial ( RCT ) and an observational cohort study , in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis . METHODS We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial ( PREVEND-IT ) and the PREVEND cohort study . The PREVEND-IT subjects ( 788 with a UAE 15 - 300 mg/day ) received pravastatin 40 mg/day vs placebo and /or fosinopril 20 mg/day vs placebo in a 2x2 factorial- RCT design . Of the 3440 cohort subjects , 469 used statins during the 4-year follow-up period . Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR . RESULTS In the RCT , pravastatin did not change UAE or GFR , neither in fosinopril yes/no subgroups . In the observational cohort , statin use was associated with a rise in UAE ( + 12.1 % ) , compared with statin non-use ( + 3.6 % , P<0.001 ) . This rise was most pronounced in those on statins prior to the first screening [ + 24.8 % ( 95 % CI : 11.9 - 39.2 ) ] , those using statins>3 years [ + 18.5 % ( 7.3 - 30.8 ) ] and those with > 1 or > 2 defined daily doses ( + 15.7 and + 17.3 % , respectively ) . These differences remained significant after adjustment for relevant variables and propensity score . The rise in UAE could not be attributed to a higher dose or a specific statin . GFR fell in 4 years in both statin users and non-users ( 4.6+/-13.5 and 2.4+/-11.2 , respectively ) . The fall in GFR between groups was not different after adjustment ( P=0.11 ) . CONCLUSIONS We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia . In the observational cohort study , the use of statins similarly was not associated with a fall in UAE ; UAE instead increased . Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR OBJECTIVES The objective of this study was to evaluate whether the regressive effects of aggressive lipid-lowering therapy with atorvastatin on coronary plaque volume ( PV ) in patients with acute coronary syndrome ( ACS ) are generalized for other statins in multicenter setting . BACKGROUND A previous single-center study reported beneficial regressive effects of atorvastatin in patients with ACS on PV of the nonculprit site by intravascular ultrasound ( IVUS ) evaluation . The effect of statins other than atorvastatin on PV has not been evaluated in the setting of ACS . METHODS The JAPAN-ACS ( Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ) study was a prospect i ve , r and omized , open-label , parallel group study with blind end point evaluation conducted at 33 centers in Japan . A total of 307 patients with ACS undergoing IVUS-guided percutaneous coronary intervention were r and omized , and 252 patients had evaluable IVUS examinations at baseline and 8 to 12 months ' follow-up . Patients were r and omly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin . The primary end point was the percentage change in nonculprit coronary PV . RESULTS The mean percentage change in PV was -16.9 + /- 13.9 % and -18.1 + /- 14.2 % ( p = 0.5 ) in the pitavastatin and atorvastatin groups , respectively , which was associated with negative vessel remodeling . The upper limit of 95 % confidence interval of the mean difference in percentage change in PV between the 2 groups ( 1.11 % , 95 % confidence interval : -2.27 to 4.48 ) did not exceed the pre-defined noninferiority margin of 5 % . CONCLUSIONS The administration of pitavastatin or atorvastatin in patients with ACS equivalently result ed in significant regression of coronary PV ( Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ; NCT00242944 ) OBJECTIVES The aim of this study was to assess for a treatment interaction between  statin use and exercise training ( ET ) response . BACKGROUND Recent data suggest that statins may attenuate ET response , but limited data exist in patients with heart failure ( HF ) . METHODS HF-ACTION ( Heart Failure : A Controlled Trial Investigating Outcomes of Exercise Training ) was a r and omized trial of 2,331 patients with chronic HF with ejection fraction ≤35 % who were r and omized to usual care with or without ET . We evaluated whether there was a treatment interaction between statins  and ET response for the change in quality of life and aerobic capacity ( peak oxygen consumption and 6-min walk distance ) from baseline to 3 months . We also assessed for a treatment interaction among atorvastatin , simvastatin , and pravastatin and change in these endpoints with ET . Multiple linear regression analyses were performed for each endpoint , adjusting for baseline covariates . RESULTS Of 2,331 patients in the HF-ACTION trial , 1,353 ( 58 % ) were prescribed statins at baseline . Patients  treated with statins were more likely to be older men with ischemic HF etiology but had similar use of renin angiotensin system blockers and beta-blockers . There was no evidence of a treatment interaction between statin use and ET on changes in quality of life or exercise capacity , nor was there evidence of differential association between statin type and ET response for these endpoints ( all p values > 0.05 ) . CONCLUSIONS In a large chronic HF cohort , there was no evidence of a treatment interaction between statin use and short-term change in aerobic capacity and quality of life with ET . These findings contrast with recent reports of an attenuation in ET response  with statins in a different population , highlighting the need for future prospect i ve studies . ( Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure ; NCT00047437 ) OBJECTIVE We evaluated the long-term effects of rosuvastatin and simvastatin on insulin sensitivity and secretion in patients with well-controlled type 2 diabetes . METHODS After a 3 weeks run-in , 27 eligible patients were r and omly assigned to receive either rosuvastatin 20 mg daily ( Group 1 ) or simvastatin 20 mg daily ( Group 2 ) for 6 months ; thereafter they were switched to the other treatment for additional 6 months . Patients were recruited among individuals attending the outpatient service of the Diabetology Unit of the " Policlinico Tor Vergata " University Hospital , Rome , Italy . Serum lipids , glucose and insulin , glycated hemoglobin , C-reactive protein , TNF-α , leptin , adiponectin , insulin sensitivity by euglycemic-hyperinsulinemic clamp , β-cells function by HOMA-β were assessed at months 0 , 6 and 12 . Additionally , endothelial function was assessed by use of the brachial artery reactivity technique . RESULTS Besides marked reduction in lipid levels , glycated hemoglobin significantly increased from baseline after 12 months in both Group 1 ( + 0.8 ± 0.2 % , p < 0.001 ) and Group 2 ( + 0.9 ± 0.3 % ; p < 0.001 ) . Similar trends were observed for fasting glucose in both groups . No changes in insulin sensitivity were detected throughout the study , whereas HOMA-β significantly decreased from baseline after 12 months in both Group 1 ( -21.9 % , p < 0.01 ) and Group 2 ( -38.9 % ; p < 0.001 ) . In addition , both treatments similarly decreased C-reactive protein and leptin , as well as improved endothelial function . No changes in anthropometric measures were observed . CONCLUSIONS In well-controlled type 2 diabetic patients  both rosuvastatin and simvastatin significantly impaired glycemic control and insulin secretion , without affecting insulin sensitivity Objective : Cardiovascular complications represent a major cause of morbidity and mortality in patients undergoing vascular surgery . This was a prospect i ve r and omized , open-label study to investigate the effect of lipid-lowering treatment by statin monotherapy or intensified by combining statin with ezetimibe on a 12-month prognosis after vascular surgery . Methods : Patients were r and omly assigned to receive rosuvastatin ( RSV ) 10 mg/d or rosuvastatin 10 mg/d plus ezetemibe ( RSV/EZT ) 10 mg/d , starting prior to scheduled surgical procedure . The primary end point was the first major cardiovascular event , including death from cardiac causes , nonfatal myocardial infa rct ion , ischemic stroke , and unstable angina . Results : A total of 136 patients assigned to RSV and 126 to RSV/EZT completed the study protocol . As many as 6.6 % of patients in the RSV group experience a major cardiovascular event within 30 days after surgery versus 5.6 % in the RSV/EZT group ( P = .72 ) . From month 1 to 12 of the follow-up period , primary end point was observed ( 9 taking RSV vs 2 in the RSV/EZT group [ P = .04 ] ) . Intensified lipid-lowering therapy with RSV/EZT was associated with a greater decrease in low-density lipoprotein cholesterol levels compared with RSV ( 75.87 ± 31.64 vs 87.19 ± 31.7 , P = .004 ) , while no differential effect on triglyceride , high-density lipoprotein cholesterol or high-sensitivity C-reactive protein levels was noted between groups . Conclusion : Our findings indicate that statin therapy intensified by ezetimibe may reduce the incidence of cardiovascular events within the first 12 months after vascular surgery . Nonetheless , whether the use of ezetimibe as an add-on therapy to reduce cardiovascular risk in these patients needs to be tested in larger future studies Introduction The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin , and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis . Methods Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients . One group ( 20 patients ) received st and ard therapy for sepsis and physiological-dose steroid therapy for 10 days ; the other group ( 20 patients ) received only st and ard therapy for sepsis .  Basal cortisol level was measured on the 14th day in patients who recovered . The outcome of sepsis was compared . Results Only Sequential Organ Failure Assessment ( SOFA ) score was found related to mortality , independent from other factors in multivariate analysis . No significant difference was found between the changes in the percentage of SOFA scores of the  steroid therapy group and the st and ard therapy group in survivors , nor between the groups in basal and peak cortisol levels , cortisol response to corticotropin test and mortality . The mortality rates among patients with occult adrenal insufficiencies were 40 % in the steroid therapy group and 55.6 % in the st and ard therapy group . Discussion There was a trend towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy . In the advancing process from sepsis to septic shock , adrenal insufficiency was not frequent as supposed . There was a trend ( that did not reach significance ) towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy Statin treatment and exercise training can reduce markers of inflammation when administered separately . The purpose of this study was to determine the effect of rosuvastatin treatment and the addition of exercise training on circulating markers of inflammation including C-reactive protein ( CRP ) , monocyte toll-like receptor 4 ( TLR4 ) expression , and CD14+CD16 + monocyte population size .  Thirty-three hypercholesterolemic and physically inactive subjects were r and omly assigned to rosuvastatin ( R ) or rosuvastatin/exercise ( RE ) groups . A third group of physically active hypercholesterolemic subjects served as a control ( AC ) . The R and RE groups received rosuvastatin treatment ( 10 mg/d ) for 20 weeks . From week 10 to week 20 , the RE group also participated in an exercise training program ( 3d/wk ) . Measurements were made at baseline ( Pre ) , week 10 ( Mid ) , and week 20 ( Post ) , and included TLR4 expression on CD14 + monocytes and CD14+CD16 + monocyte population size as determined by 3-color flow cytometry . Serum CRP was quantified by enzyme-linked immunosorbent assay . TLR4 expression on CD14 + monocytes was higher in the R group at week 20 . When treatment groups ( R and RE ) were combined , serum CRP was lower across time . Furthermore , serum CRP and inflammatory monocyte population size were lower in the RE group compared with the R group at the Post time point . When all groups ( R , RE , and AC ) were combined , TLR4 expression was greater on inflammatory monocytes ( CD14+CD16 + ) compared with classic monocytes ( CD14+CD16⁻ ) at all time points . In conclusion , rosuvastatin may influence monocyte inflammatory response by increasing TLR4 expression on circulating monocytes . The addition of exercise training to rosuvastatin treatment further lowered CRP and reduced the size of the inflammatory monocyte population , suggesting an additive anti-inflammatory effect of exercise The very first rigorously design ed , r and omized controlled trial ( RCT ) in the history of modern medicine was published in 1948 . The study , design ed and carried out by the Streptomycin in Tuberculosis Trials Committee of the Medical Research Council , demonstrated the efficacy of streptomycin in treating pulmonary tuberculosis on top of bed rest , which was the best available treatment at that time.1 In the field of hypertension treatment and cardiovascular prevention , the history of event-based RCTs began in 1967 , when the cardiovascular benefits and risks of antihypertensive drug treatment were evaluated in the setting of the Veterans Administration Cooperative Study in Hypertension.2 In that trial , 143 patients with severe hypertension were r and omized to receive blood pressure (BP)–lowering drug treatment or matched placebo for 11 months . A major morbid or fatal event was observed in 26 of 70 patients who received placebo ( 37 % ) and in only 1 of 73 patients under active treatment ( 1 % ) . The amazing results of this l and mark trial established beyond any doubt the striking cardiovascular benefits of antihypertensive drug treatment of hypertension at a time when controversy still persisted regarding the supposedly deleterious effects of BP reduction on organ perfusion.3 Ever since , RCTs have represented a formidable tool for evaluating risks and benefits of hypertension treatment . Over the past 50 years , the remarkable progress in treatment and control of high BP , one of the most outst and ing achievements of modern medicine , has been driven by the results of many large , event-based RCTs . The influential position of RCTs in clinical and therapeutic research as opposed to real-world observational studies ( surveys , registries , and retrospective analyses of existing data bases ) originates from their high internal validity ( ie , the power to address clinical questions with a low level of internal bias ) . A list of strengths and weaknesses of RCTs and observational studies is In a framework of multicenter study ATLANTIKA in a group of patients we carried out noninvasive ultrasound test of endothelium dependent vasodilatation ( EDVD ) of brachial artery before and at the background of therapy with atorvastatin . Aim of the study was to assess and compare effects of incremental ( 10 - 80 mg/day ) and stable ( 10 mg/day ) doses of atorvastatin on functional state of endothelium . The group of observation comprised 148 patients A 86 men , 62 women aged 59.5 ( 55;66 ) years , who were included into ATLANTIKA study and r and omized to 3 groups : group A - active therapy with stable dose of atorvastatin ( 10 mg/day ) ( n=52 ) , active therapy with titration of atorvastatin dose from 10 to 80 mg/day ( n=50 ) , group C - common therapy which could include lipid lowering drugs ( n=46 ) . At baseline there were no statistically significant differences between groups in main demographical , laboratory and instrumental parameters . Median EDVD was 5.4 ( 3.5 ; 8.0 ) , 5.1 ( 3.9 ; 7.6 ) and 5.6 ( 3.2 ; 8.1)% in groups A , B , and C , respectively . After 12 and 24 weeks of observation statistically significant increases of brachial artery EDVD occurred only in group B ( by 27.2 and 31.9 % , respectively ) . There was no statistically significant positive dynamics of EDVD in groups A and C. Results of the presented work show that for achievement of statistically significant positive vascular effect it is necessary to titrate dose of atorvastatin until target level of low density lipoprotein cholesterol ( < 2.5 mmol/l ) is achieved . Vascular effect of therapy with atorvastatin in a fixed dose 10 mg/day is inferior to that of aggressive therapy , however it is substantially superior to common treatment ABSTRACT Objectives : In a 24-week , open-label , r and omized , parallel-group study , we compared the efficacy and metabolic effects , beyond low density lipoprotein cholesterol (LDL-C)-lowering , of atorvastatin ( ATV ) and rosuvastatin ( RSV ) in cardiovascular diseasefree subjects with primary hyperlipidaemia , treated to an LDL-C target ( 130 mg/dL ) . Methods : After a 6‐week dietary lead-in period , patients were r and omized to RSV 10 mg/day ( n = 60 ) or ATV 20 mg/day ( n = 60 ) . After 6 weeks on treatment the dose of the statin was increased ( to RSV 20 mg/day or ATV 40 mg/day ) if the treatment goal was not achieved . A control group of healthy volunteers ( n = 60 ) was also included for the validation of baseline serum and urinary laboratory parameters . The primary outcome was the percentage of patients reaching the LDL‐C goal ; secondary outcomes were changes in lipid and non-lipid metabolic parameters . Results : A total of 45 patients ( 75.0 % ) in the RSV-treated group and 43 ( 71.7 % ) in the ATV-treated group achieved the treatment target at the initial dose . Both regimens were generally well tolerated and there were no withdrawals due to treatment-related serious adverse events . Similar significant reductions in total cholesterol , LDL‐C , apolipoprotein ( apo ) B , triglycerides , apoB/apoA1 ratio , fibrinogen and high-sensitivity C‐reactive protein levels were seen . RSV had a significant high density lipoprotein cholesterol (HDL‐C)-raising effect and showed a trend towards increasing apoA1 levels . Glycaemic control and renal function parameters were not influenced by statin therapy . ATV , but not RSV , showed a significant hypouricaemic effect . Conclusions : RSV and ATV were equally efficacious in achieving LDL‐C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration . RSV seems to have a significantly higher HDL‐C-raising effect , while ATV lowers serum uric acid levels
In the meta-regression analysis , changes in plasma cortisol concentrations following statin therapy were found to be independent of treatment duration .
Results of this meta- analysis of RCTs suggest a significant elevation in plasma cortisol levels following statin therapy
This study aim ed to perform a systematic review and meta- analysis of r and omized controlled trials ( RCTs ) in order to calculate the effect size of statin therapy in changing plasma cortisol concentrations .