Atorvastatin versus Four Statin–Fibrate Combinations in Patients with Familial Combined Hyperlipidaemia N-3 fatty acid supplementation decreases plasma homocysteine in diabetic dyslipidemia treated with statin-fibrate combination. Short-term recovery pattern of plasma fibrinogen after cardiac surgery: A prospective observational study Bezafibrate and simvastatin combination therapy for diabetic dyslipidaemia: efficacy and safety. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. Effects of Antiadhesion preparation on free fibrinogen and fibrin degrading products in abdominal exudates of rabbits postoperatively. Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review Effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen in hyperlipidaemic patients. Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia Kaolin‐activated thromboelastography and standard coagulation assays in cyanotic and acyanotic infants undergoing complex cardiac surgery: a prospective cohort study Lipoprotein(a) in American Indians is low and not independently associated with cardiovascular disease. The Strong Heart Study. The influence of statin-fibrate combination therapy on lipids profile and apolipoprotein A5 in patients with acute coronary syndrome Effect of simvastatin and fenofibrate on endothelium in Type 2 diabetes. Prolonged statin administration does not act on the cell-mediated immunity of HIV-infected dyslipidemic patients treated with a steady and effective highly active antiretroviral therapy. A two-year prospective study of statin versus fibrate administration. Ten-year all-cause mortality in presumably healthy subjects on lipid-lowering drugs (from the Prospective Epidemiological Study of Myocardial Infarction [PRIME] prospective cohort). Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. Effects of atorvastatin versus fenofibrate on lipoprotein profiles, low-density lipoprotein subfraction distribution, and hemorheologic parameters in type 2 diabetes mellitus with mixed hyperlipoproteinemia. Lipid lowering agents, cognitive decline, and dementia: the three-city study. [Effects of thromboprophylaxis duration on coagulation indicators after total hip replacement]. Efficacy of combination of atorvastatin and micronised fenofibrate in the treatment of severe mixed hyperlipidemia Statins and the risk of pneumonia: a population-based, nested case-control study. Hemostatic effects of bezafibrate and ω-3 fatty acids in isolated hypertriglyceridemic patients. Modulation of plasma fibrinogen levels by ciprofibrate and gemfibrozil in primary hyperlipidaemia.
Background Statin – fibrate combinations are very effective in the treatment of familial combined hyperlipidaemia ( FCHL ) . Nonetheless , they have not been extensively used because of the fear of side effects . Thus , a therapeutic alternative is required for this lipid disorder . Objective To compare the long-term ( one-year ) efficacy of atorvastatin monotherapy with those of four statin – fibrate combinations in 675 FCHL patients . Methods Patients were r and omly assigned to atorvastatin monotherapy ( A 20 mg/day ) n=134 , or pravastatin ( P 20 mg/day)+gemfibrozil ( G 1200 mg/day ) n=135 , simvastatin ( S 20 mg/day)+G ( 1200 mg/day ) n=137 , P ( 20 mg/day)+ciciprofibrate ( C 100 mg/day ) n=135 , and S ( 20 mg/day)+C ( 100 mg/day ) n=134 . Results Twelve patients on statin – fibrate combinations were withdrawn from the study because of side effects : Three because of CK elevation , two because of myalgia and seven due to increase in serum transaminase levels . One patient on A was withdrawn because of persistent epigastric discomfort .  Atorvastatin  reduced low density lipoprotein cholesterol and apoprotein B more than all four combinations ( −45 % vs. maximum −40 % of S+C , and −39 % vs. maximum −32 % of the same combination , respectively , P < 0.001 for both ) , but had a lesser effect on triglycerides ( −38 % vs. maximum −53 % of S+C , P=0.0002 ) and high density lipoprotein cholesterol ( 6 % vs. maximum 21 % of S+G , P=0.0003 ) . The effect of A on plasma fibrinogen was analogous to that of G combinations ( −8 % vs. −9 % of P+G and −11 % of S+G , P = NS vs. baseline and among each other ) and inferior to that of the ciprofibrate combinations ( −8 % vs. −24 % of P+C , P=0.0002 and −26 % S+C , P=0.0001 ) . A had a lower treatment cost and better patient compliance , P=0.04 vs. C combinations and P=0.02 vs. G combinations . Conclusions The data suggest that statin – fibrate combinations have a beneficial effect on all lipid parameters . Atorvastatin monotherapy has a better effect on LDL-C and apoprotein B than statin – fibrate combinations , but a lesser effect on HDL-C , TG and in the case of ciprofibrate combinations , fibrinogen . The clinical significance of these findings should be tested in a large , long-term survival study The aim of this study was to study the effect of adding polyunsaturated fatty acid ( PUFA ) n-3 or placebo ( containing oleic acid ) to a combined statin-fibrate treatment on plasma lipoproteins , lipoperoxidation , glucose homeostasis , total homocysteine ( tHcy ) and microalbuminuria ( MA ) in patients with diabetic dyslipidemia ( DDL ) . Twenty-four patients , who did not fulfill the recommended target lipid values with combined hypolipidemic therapy ( pravastatin 20 mg+micronized fenofibrate 200 mg daily ) , were supplemented with 3.6 g PUFA n-3 daily for 3 months or placebo ( olive oil ) for the next 3 months . The concentrations of plasma lipids , fatty acid ( FA ) profiles of phosphatidylcholine ( PC ) , cholesteryl esters ( CE ) and triglycerides ( TG ) , tHcy levels , concentrations of conjugated dienes ( CD ) in low-density lipoprotein ( LDL ) , and MA were determined in baseline state , after the PUFA n-3 and placebo treatment period . Supplementation with PUFA n-3 led to a significant decrease in plasma tHcy ( -29 % , P < .01 ) and TG ( -28 % , P < .05 ) levels , as well as to a significant decrease in MA ( -24 % , P < .05 ) . The decrease in MA correlated significantly with the increase in total PUFA n-3 ( r = -.509 , P < or = .05 ) and docosahexaenoic acid ( r = -.52 , P < .01 ) in TG . The concentrations of CD in LDL increased significantly ( + 15 % , P < .05 ) . The supplementation with PUFA n-3 to the combined statin-fibrate treatment in patients with DDL decreased the TG and tHcy levels as well as MA . It could lead to decreased risk of atherothrombosis and delay of diabetic nephropathy onset and progression Low plasma fibrinogen level is common after  cardiopulmonary bypass ( CPB ) .  Current substitution practice with fibrinogen concentrate generally follows a single measurement and cut-off values from the literature , whereas early postoperative endogenous fibrinogen kinetics is incompletely described and widely disregarded . The aim of this study was to determine the short-term recovery pattern of plasma fibrinogen after CPB weaning . Our hypothesis was that in the absence of surgical bleeding , CPB-induced hypofibrinogenemia would resolve spontaneously and predictably within a few hours . In a prospect i ve , observational study of 26 patients undergoing conventional CPB ( cCPB ) or minimally invasive extracorporeal circulation ( MiECC )  , Clauss fibrinogen level ( C-FIB ) was determined at 10 closely spaced time points after protamine administration . Primary endpoint was the time to recovery of post-CPB fibrinogen levels to ≥1.5 g/L. C-FIB reached its nadir after protamine administration corresponding to 62 ± 5 % ( mean ± SD ) of the baseline level after cCPB and 68 ± 7 % after MiECC ( p = 0.027 vs. cCPB ) . C-FIB recovered spontaneously at a nearly constant rate of approximately 0.08 g/L per hour . In all patients , C-FIB was ≥1.5 g/L at 4 hours and ≥2.0 g/L at 13 hours after CPB weaning . Following cardiac surgery with CPB and in the absence of surgical bleeding , spontaneous recovery of normal endogenous fibrinogen levels can be expected at a rate of 0.08 g/L per hour . Administration of fibrinogen concentrate triggered solely by a single-point measurement of low plasma fibrinogen some time after CPB is not justified OBJECTIVE To determine the efficacy and safety of a statin-fibrate combination in diabetes patients . DESIGN . : An open 21-month trial in which each patient first received the single drug for 6 months and then a combination of the two for 1 year . SETTING Three lipid clinics in university-based tertiary care hospitals . PATIENTS One hundred and forty-eight patients with type 2 ( non-insulin-dependent , NIDDM ) diabetes mellitus under stable control for 3 months by means of diet and oral hypoglycaemic medication . INTERVENTION Patients from one clinic ( n = 48 ) received bezafibrate slow release ( 400 mg day-1 ) , and patients from the other two clinics ( n = 100 ) received simvastatin 20 mg day-1 . Six months later , all patients were switched to a daily combination of 400 mg bezafibrate slow release and 20 mg simvastatin for 1 year . RESULTS The combination of statin and fibrate led to a 23 % reduction in total cholesterol , 42 % reduction in triglycerides , 29 % reduction in LDL-c , 25 % increase in HDL-c , 10 % decrease in fibrinogen and 19 % reduction of Lp(a ) levels , and a decrease in the cholesterol/HDL-c ratio ( from 8.9 to 5.4 ) in all 148 patients . Cardiovascular ( CV ) event rate was significantly reduced from 9.5 % during the first 6 months of the study to less than 2 % during the last year of the study ( whilst on combination Rx ) . Side-effects with all treatments included only two patients who developed myopathy when on the combined regimen and one on the single statin regimen . However , plasma creatinine phosphokinase ( CPK ) levels doubled ( but remained within the normal range ) in most of the patients on combination therapy , compared with only a mild increase in patients receiving a single medication . CONCLUSIONS The statin and fibrate combination was found to be more efficacious than a single medication for treatment of diabetic dyslipidaemia , as evidence d by improvement in the lipoprotein profile , reductions in Lp(a ) , fibrinogen and CV event rate , and almost no clinical ly significant side-effects OBJECTIVES We compared vascular and metabolic responses ( and adverse responses ) to statin and fibrate therapies alone or in combination in patients with combined hyperlipidemia . BACKGROUND The mechanisms of action for statins and fibrates are distinct . METHODS Fifty-six patients were given atorvastatin 10 mg and placebo , atorvastatin 10 mg and fenofibrate 200 mg , or fenofibrate 200 mg and placebo daily during each two-month treatment period of a r and omized , double-blind , placebo-controlled crossover trial with two washout periods of two months ' each . RESULTS Lipoproteins were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone . Flow-mediated dilator response to hyperemia and plasma high-sensitivity C-reactive protein and fibrinogen levels were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone ( p < 0.001 , p = 0.182 , and p = 0.015 by analysis of variance [ ANOVA ] , respectively ) . The effects of combined therapy or fenofibrate alone on plasma adiponectin levels and insulin sensitivity ( determined by the Quantitative Insulin-Sensitivity Check Index [ QUICKI ] ) were significantly greater than those of atorvastatin alone ( p = 0.022 for adiponectin and p = 0.049 for QUICKI by ANOVA ) . No patients were withdrawn from the study as the result of serious adverse effects . CONCLUSIONS Combination therapy is safe and has beneficial additive effects on endothelial function in patients with combined hyperlipidemia AIM To observe effects of ACOL on fibrinogen ( FIB ) , fibrin degrading products ( FDP ) and changes of FIB and FDP concentration in rabbits with intro-abdominal exu date s during 7 d after major abdominal surgery . METHODS Sixty New Zeal and rabbits were r and omly divided into 4 groups : ACOL group , the control group , DCT group and the normal group . After being modeled , except the normal group , the other 3 groups were treated with different ways for a week ; the intro-abdominal exu date s of rabbits in the 4 groups were drawn for FIB and FDP measurement once daily during 7 d after major abdominal surgery . RESULTS FIB and FDP in the intro-abdominal exu date s altered in a regular way and ACOL could change the concentration of FIB and FDP in the intra-abdominal exu date s after major abdominal surgery . CONCLUSION ACOL can prevent intestinal adhesion by reducing the concentration of FIB and raising that of FDP in the intro-abdominal exu date s after major abdominal surgery Background Diabetic retinopathy ( DR ) is a common microvascular complication of diabetes mellitus , and more than 75 % of patients who have had diabetes for more than 20 years will have some degree of DR . This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age . The current mainstay of treatment is laser photocoagulation , which causes impairment of vision and discomfort to patients . Thus , finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable . Objective To assess the efficacy and safety of the drugs in the statin and /or fibrate groups for the prevention and treatment of DR . Methods In this systematic review , we will select r and omized controlled trials of fibrates or statins used for the treatment or prevention of DR . Our search strategy will include free text terms and controlled vocabulary ( eg , MeSH , Emtree ) for , “ diabetic retinopathy ” , “ statins ” , “ fibrates ” , “ hypolipidemic agents ” , and for drugs from both groups . Data bases that will be used include Medical Literature Analysis and Retrieval System/ PubMed , Embase , Cochrane Central Register of Controlled Trials , Latin American and Caribbean Center on Health Sciences Information , Clinical trials.gov , World Health Organization International Clinical Trials Registry Platform , and OpenGrey , and we will not have language or date limits . Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration ’s tool . We will report structured summaries of the included studies and , if possible , conduct meta-analyses . Results This is a protocol for a systematic review , therefore results are not available . We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion . Conclusions Intensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients . Both macrovascular and microvascular events in diabetic patients appear to have a common pathway , starting with endothelial injury . Thus , prevention and treatment of microvascular events may benefit from the same interventions . In the review for which we have written this protocol , we will assess whether the use of lipid-lowering oral drugs of the statin and /or fibrate groups may prevent and /or retard progression of DR , with the added benefit of preserving visual acuity . Trial Registration PROSPERO Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects . A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent . We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator ( t-PA ) , plasminogen activator inhibitor-1 ( PAI-1 ) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen . Although both fibrates effectively lowered triglyceride and cholesterol levels , no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment . However , both fibrates influenced plasma fibrinogen levels , albeit in a different way . Fibrinogen antigen levels were elevated by 17.6 % ( p < 0.05 ) and 24.3 % ( p < 0.001 ) with gemfibrozil after six and twelve weeks , respectively , whereas with ciprofibrate there was no effect . Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point , no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment . However , after twelve weeks , gemfibrozil enhanced functional fibrinogen levels by 7.2 % ( p < 0.05 ) as assessed by the Clauss mechanical assay , but decreased functional fibrinogen levels by 12.5 % ( p < 0.0001 ) when a Clauss assay based on turbidity was used . After six or twelve weeks of ciprofibrate treatment , functional fibrinogen levels were decreased by 10.1 % ( p < 0.001 ) and 10.5 % ( p < 0.0001 ) , respectively on the basis of Clauss mechanical and by 14.2 % ( p < 0.001 ) and 28.2 % ( p < 0.0001 ) , respectively with the Clauss turbidimetric assay . A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen ( determined by either of the two Clauss assays ) to fibrinogen antigen . Taken together , our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates , by differences in treatment period and /or by the different outcomes of various assay systems . Interestingly , the two fibrates tested both reduced the functionality of fibrinogen Five multicenter , r and omized , double‐blind , placebo‐controlled studies were conducted in France to compare the efficacy and safety of once‐daily simvastatin treatment ( 10–40 mg/day ) with conventional therapy with gemfibrozil 900 mg/day , ciprofibrate 100 mg/day , bezafibrate 400 mg/day , and fenofibrate 300 or 400 mg/day in a total of 800 patients with hypercholesterolemia .  Simvastatin was associated with statistically significantly greater ( p ≪ 0.01 ) mean percent reductions in plasma low‐density lipoprotein ( LDL ) cholesterol compared with each of the five fibrate regimens , even when administered at its recommended starting dose of 10 mg/day . Furthermore , approximately 90 % of patients treated once daily with simvastatin experienced an at least 20 % decrease in plasma LDL cholesterol compared with only 36 to 68 % of patients treated with the individual fibrate agents ( p ≪ 0.05 ) . The effectiveness of simvastatin in reducing LDL cholesterol did not differ as a function of the baseline plasma concentrations of total cholesterol or triglycerides . In contrast , the effectiveness of fibrate therapy in lowering plasma LDL cholesterol levels was significantly diminished ( p ≪ 0.05 ) among patients with triglyceride concentrations  >  1.7 mmol/1 . Plasma highdensity lipoprotein ( HDL ) cholesterol levels were increased by approximately 10 % after treatment with simvastatin or the fibrates . Although fibrate therapy was more effective overall in lowering plasma triglyceride levels , the effectiveness of simvastatin in reducing plasma triglyceride levels was generally 2‐ to 4‐fold greater in patients with hypercholesterolemia associated with triglyceride levels ≫ 2.3 mmol/1 than in those with hypercholesterolemia associated with triglyceride levels < 2.3 mmol/1 . The results of these studies confirm the superiority of simvastatin to st and ard fibrate therapy in reducing plasma levels of total and LDL cholesterol . They further indicate that once‐daily treatment with simvastatin is effective in patients with isolated hypercholesterolemia or hypercholesterolemia associated with elevated triglyceride levels BACKGROUND AND AIMS Several studies report the use of  thromboelatography ( TEG ) to monitor coagulation in pediatric cardiac surgery . The aim of this study was to compare baseline and intraoperative TEG , TEG-functional fibrinogen , and st and ard coagulation assays in children with cyanotic and acyanotic congenital heart disease ( CHD ) undergoing cardiac surgery . METHODS This is a prospect i ve observational study of 63 children aged < 24 months undergoing cardiac surgery with cardiopulmonary bypass ( CPB ) .  Exclusion criteria included preoperative anticoagulant therapy and hepatic failure . We collected blood at anesthesia induction ( T1 ) , at lowest temperature after CPB start ( T2 ) , and after heparin neutralization ( T3 ) .  Coagulation was evaluated by  TEG ( reaction time [ R ] ) , k , alpha-angle , maximum amplitude ( MA ) , MA-fibrinogen ( MA-fib ) , and by st and ard coagulation assays ( prothrombin time , activated partial thromboplastin time , fibrinogen level , platelet [ PLT ] count ) . RESULTS Sixty-three patients were enrolled ( 38 cyanotic and 25 acyanotic ) . Median age was 4 [ IQR 2 - 6 ] months and median weight was 5 [ IQR 3.7 - 6.5 ] kg . Most common surgeries were : ventricular septal defect repair ( n = 13 ) , Fallot correction ( n = 11 ) , and arterial switch operation ( n = 10 ) . Cyanotic and acyanotic children were well matched : R , k , MA , and MA-fib at T1 , T2 , and T3 were not significantly different between cyanotic and acyanotic children . At T2 , significant correlations were showed between MA and PLT count ( r = 0.4 ; P = 0.0008 ) and k and plasma fibrinogen level ( r = -0.54 ; P < 0.0001 ) . At T3 , significant correlations were showed between MA and PLT count ( r = 0.5 ; P < 0.0001 ) , G and PLT count ( r = 0.6 ; P < 0.0001 ) , and MA-fib and plasma fibrinogen level ( r = 0.5 ; P = 0.002 ) . CONCLUSIONS According to our findings , cyanosis does not affect TEG parameters in children with CHD . PLT count and plasma fibrinogen significantly correlated ( are significantly associated ) with MA and MA-fib respectively , suggesting that use of TEG after protamine administration may be prompted for improved hemostatic monitoring in the perioperative phase PURPOSE To evaluate the distribution of  lipoprotein(a ) ( Lp(a ) ) and assess its association to cardiovascular disease ( CVD ) in American Indians . METHODS  Lp(a )  was measured in 3991 American Indians ( aged 45 - 74 years with no prior history of CVD at baseline ) from 13 communities in Arizona , Oklahoma , and South/North Dakota . They were followed prospect ively from 1989 to 1997 for CVD . The distribution of Lp(a ) was examined by center , sex , and diabetic status . Spearman correlation coefficients and Cox regression models were used to evaluate the association of Lp(a ) to CVD . RESULTS A total of 388 participants subsequently developed CVD .  Median Lp(a ) concentration in American Indians was 3.0 mg/dl . This was almost half of that in whites and one sixth in blacks from the CARDIA study measured by the same method . Nondiabetic participants had significantly higher Lp(a ) levels than diabetic participants for both genders . Lp(a ) levels were higher in women than in men for nondiabetic participants , but there was no gender difference for diabetic participants . Correlation analysis showed Lp(a ) was significantly negatively correlated with the degree of Indian heritage , insulin , triglycerides ( TG ) , fasting plasma glucose ( FPG ) , and 2-hour plasma glucose ( 2hPG ) , and positively with low-density lipoproteins ( LDL ) , apoprotein B ( apoB ) , and fibrinogen ( FIB ) . In Cox regression models , adjusting for other risk factors , Lp(a ) was no longer a significant predictor of CVD in either diabetic or nondiabetic participants . CONCLUSIONS The lower concentration of Lp(a ) in American Indians and the high correlation with Indian heritage confirm the concept that Lp(a ) concentration is in large part genetically determined . Lp(a ) concentration is not an independent predictor of CVD among American Indians ; it is higher in those who develop CVD because of its positive correlation with LDL , apoB , and FIB Background Statin-fibrate combination therapy has been used to treat patients with acute coronary syndrome ( ACS ) complicated by elevated triglycerides ( TG ) and decreased high density lipoprotein cholesterol ( HDL-C ) . The purpose of this study was to evaluate the influence of the combination therapy on lipids profile and apolipoprotein A5 ( apoA5 ) level in patients with ACS . Methods One hundred and four patients with ACS were recruited and r and omly assigned into two groups : one was statin group ( n = 52 ) , given atorvastatin ( 20 mg QN ) or other statins with equivalent dosages ; the other was combination group ( n = 52 ) , given the same dose of statin plus bezafibrate ( 200 mg BID ) . Follow-up visits were scheduled at the end of 6 and 12 weeks post treatment . Serum apoA5 levels were determined using a commercial available ELISA kit . Results ( 1 ) Compared with that of statin monotherapy , statin-bezafibrate combination treatment not only result ed in a significant reduction of TG , TC and LDL-C levels , ( all p < 0.05 ) , but also led to increases in HDL-C and apoA5 levels ( p < 0.05).(2 ) The percentage changes of TC , TG , LDL-C and apoA5 levels in both groups were even bigger at 12 weeks after treatment than that at 6 weeks ( all p < 0.05 ) . Similarly , the rates of achieving lipid-control target were higher in statin-bezafibrate combination treatment group than those in statin monotherapy group ( all p < 0.05).(3 ) Spearman rank correlation analysis showed that the pre-treatment apoA5 level was positively correlated with TG ( r = 0.359 , p = 0.009 ) . However , a negative correlation was observed between apoA5 and TG ( r = -0.329 , p = 0.017 ) after 12 weeks treatment . Conclusions Statin and fibrate combination therapy is more effective than statin alone in achieving a comprehensive lipid control for ACS patients .  Serum apoA5 elevation after statin and fibrate combination treatment could be due to the synergistic effect of both drugs on hypertriglyceridemia control Statins and fibrates influence endothelial activity and consequently atherogenesis but the mechanisms are not well understood . Twenty Type 2 diabetic patients with dyslipidemia were treated 3 months with simvastatin ( 20 mg daily ) and then 3 months with fenofibrate ( 200 mg daily ) with 2 months of wash-out between the two treatments . Laboratory parameters of oxidative stress , fibrinolysis and endothelial function were evaluated before and at the end of each treatment period . The significant decrease in serum total and LDL-cholesterol concentrations ( P<0.0001 ) caused by simvastatin was associated with an increase in serum N-acetyl-beta-glucosaminidase activity ( P<0.001 ) , ascorbic acid ( P<0.001 ) , plasminogen activator inhibitor ( PAI-1 ) ( P<0.01 ) , vonWillebr and factor ( P<0.05 ) , E-selectin ( P<0.01 ) and vascular endothelial growth factor ( P<0.05 ) concentrations and with a decrease in plasma glutathione ( P<0.01 ) levels . Fenofibrate caused a significant decrease in serum triglyceride concentration ( P<0.0001 ) associated with a decrease in plasma malondialdehyde ( P<0.001 ) and an increase in plasma PAI-1 ( P<0.05 ) and P-selectin ( P<0.05 ) concentrations . We conclude that simvastatin and fenofibrate interact , by different mechanisms , with oxidative stress , a key factor in the modification of fibrinolysis and endothelial function in Type 2 diabetes OBJECTIVE To assess whether statin administration for HIV-associated hyperlipidemia has long-term effects on immune recovery ( as expressed by the trend of mean CD4 + lymphocyte count ) , in patients on a virologically-active HAART regimen since 12 months or more . METHODS Single-centre , open-label , prospect i ve study of 301 hyperlipidemic patients treated with statins ( 99 cases , with a predominant hypercholesterolemia ) , fibrates ( 116 subjects , when hypertriglyceridemia prevailed ) , or a isolated dietary/exercise program ( 86 patients , used as a control group ) . Neither epidemiological nor clinical , virological , or immunological differences were detected among the three study groups at baseline . During the subsequent follow-up , patients were excluded from evaluation should virological efficacy was not maintained , and /or initial hypolipidemic therapy was modified or interrupted for any reason . RESULTS The quarterly assessment of mean CD4 + lymphocyte count did not disclose any statistically significant difference among the three study groups , since baseline and until at least 24 consecutive months of follow-up . Our data tend to exclude relevant in vivo negative activities of statins on immune system recovery of HIV-infected individuals who undergo a virologically effective HAART treatment . CONCLUSIONS Multiple , pleiotropic features have been attributed to both statins and fibrates , and also apparently significant effects on laboratory markers of HIV disease progression have been recently cl aim ed or expected . Despite some preliminary in vitro and ex-vivo models , both the main hypolipidemic classes administered for the management of HIV-related dyslipidemia ( both statins and fibrates ) do not seem to act significantly on clinical immune response of patients successfully treated with HAART . Multifactorial pathways are expected to interact with the cell-mediated immune system of HIV-infected patients undergoing successful HAART , and further studies are needed to eluci date whether more subtle immune effects might be prompted by a long-term administration of hypolipidemic drugs in this speciasl setting Lipid-lowering drugs are one of the most prescribed drugs worldwide . The aim was to compare 10-year all-cause mortality according to initial dyslipidemia status and lipid-lowering drug exposure . The PRIME study was a multicenter population -based prospect i ve cohort study of men recruited in 1991 to 1993 , aged 50 to 59 years at baseline , and followed up for 10 years . The 4 groups compared were  normolipidemic , untreated dyslipidemic , and dyslipidemic subjects on fibrate or statin therapy . Data were analyzed using multivariate Cox models . The cohort included 7,722 French men ( statin  group 4.0 % , fibrate group 7.9 % ,  untreated dyslipidemic  subjects 19.0 % , and normolipidemic subjects 69.1 % ) . After 10 years , 4.8 % of the sample was lost to follow-up and 416 deaths occurred ( cancers 53.1 % , cardiovascular diseases 17.1 % , and other 29.8 % ) . After adjustment for center , age , educational level , cardiovascular risk factors , lipids , alcohol intake , and history of cardiovascular and severe chronic diseases , hazard ratios ( HRs ) for all-cause mortality were 0.49 ( 95 % confidence interval [ CI ] 0.26 to 0.94 , p = 0.031 ) for subjects treated with a statin , 0.65 ( 95 % CI 0.42 to 0.99 , p = 0.046 ) for those on fibrate therapy , and 0.76 ( 95 % CI 0.56 to 1.03 , p = 0.080 ) for normolipidemic men compared with untreated dyslipidemic subjects . In the statin group , HRs for death from cardiovascular disease , cancer , and other causes were 0.55 ( p = 0.348 ) , 0.41 ( p = 0.067 ) , and 0.68 ( p = 0.546 ) compared with dyslipidemic subjects , respectively . In the fibrate group , HRs were 0.76 ( p = 0.499 ) , 0.52 ( p = 0.041 ) , and 0.87 ( p = 0.746 ) . In conclusion , in this cohort study carried out in a real-life setting , all-cause mortality was significantly lower in dyslipidemic subjects on fibrate or statin therapy than in untreated dyslipidemic patients . No excess risk of noncardiovascular death was observed In view of the evidence linking plasma high density lipoprotein (HDL)-cholesterol levels to a protective effect against coronary artery disease and the widespread use of fibrates in the treatment of hyperlipidemia , the goal of this study was to analyze the influence of fibrates on the expression of apolipoprotein ( apo ) A-II , a major protein constituent of HDL . Administration of fenofibrate ( 300 mg/d ) to 16 patients with coronary artery disease result ed in a marked increase in plasma apo A-II concentrations ( 0.34 + /- 0.11 to 0.45 + /- 0.17 grams/liter ; P < 0.01 ) . This increase in plasma apo A-II was due to a direct effect on hepatic apo A-II production , since fenofibric acid induced apo A-II mRNA levels to 450 and 250 % of control levels in primary cultures of human hepatocytes and in human hepatoblastoma HepG2 cells respectively . The induction in apo A-II mRNA levels was followed by an increase in apo A-II secretion in both cell culture systems . Transient transfection experiments of a reporter construct driven by the human apo A-II gene promoter indicated that fenofibrate induced apo A-II gene expression at the transcriptional level . Furthermore , several other peroxisome proliferators , such as the fibrate , Wy-14643 , and the fatty acid , eicosatetraynoic acid ( ETYA ) , also induced apo A-II gene transcription . Unilateral deletions and site-directed mutagenesis identified a sequence element located in the J-site of the apo A-II promoter mediating the responsiveness to fibrates and fatty acids . This element contains two imperfect half sites spaced by 1 oligonucleotide similar to a peroxisome proliferator responsive element ( PPRE ) . Cotransfection assays showed that the peroxisome proliferator activated receptor ( PPAR ) transactivates the apo A-II promoter through this AII-PPRE . Gel retardation assays demonstrated that PPAR binds to the AII-PPRE with an affinity comparable to its binding affinity to the acyl coA oxidase (ACO)-PPRE . In conclusion , in humans fibrates increase plasma apo A-II concentrations by inducing hepatic apo A-II production . Apo A-II expression is regulated at the transcriptional level by fibrates and fatty acids via the interaction of PPAR with the AII-PPRE , thereby demonstrating the pivotal role of PPAR in controlling human lipoprotein metabolism Diabetic dyslipoproteinemia characterized by hypertriglyceridemia , low high-density lipoprotein ( HDL ) cholesterol , and often elevated low-density lipoprotein ( LDL ) cholesterol with predominance of small , dense LDL is a strong risk factor for atherosclerosis . It is unclear whether fibrate or statin therapy is more effective in these patients . We compared atorvastatin ( 10 mg/day ) with fenofibrate ( 200 mg/day ) , each for 6 weeks separated by a 6-week washout period in 13 patients ( 5 men and 8 women ; mean age 60.0+/-6.8 years ; body mass index 30.0+/-3.0 kg/m2 ) with type 2 diabetes mellitus ( hemoglobin A1c 7.3+/-1.1 % ) and mixed hyperlipoproteinemia ( LDL cholesterol 164.0+/-37.8 mg/dl , triglycerides 259.7+/-107 mg/dl , HDL cholesterol 48.7+/-11.0 mg/dl ) using a r and omized , crossover design . Lipid profiles , LDL subfraction distribution , fasting plasma viscosity , red cell aggregation , and fibrinogen concentrations were determined before and after each drug . Atorvastatin decreased all LDL subfractions ( LDL cholesterol , -29 % ; p < 0.01 ) including small , dense LDL .  Fenofibrate predominantly decreased triglyceride concentrations ( triglycerides , -39 % ; p < 0.005 ) and induced a shift in LDL subtype distribution from small , dense LDL ( -31 % ) to intermediate-dense LDL ( + 36 % ) . The concentration of small , dense LDL was comparable during therapy to both drugs ( atorvastatin 62.8+/-19.5 mg/dl , fenofibrate 63.0+/-18.1 mg/dl ) . Both drugs induced an increase in HDL cholesterol  ( atorvastatin + 10 % , p < 0.05 ; fenofibrate + 11 % , p = 0.06 ) . In addition , fenofibrate decreased fibrinogen concentration ( -15 % , p < 0.01 ) associated with a decrease in plasma viscosity by 3 % ( p < 0.01 ) and improved red cell aggregation by 15 % ( p < 0.05 ) , whereas atorvastatin did not affect any hemorheologic parameter . We conclude that atorvastatin and fenofibrate can improve lipoprotein metabolism in type 2 diabetes . However , the medications affect different aspects of lipoprotein metabolism The aim of this prospect i ve cohort study was to evaluate the effects of lipid lowering agent ( LLA ) intake on cognitive function in 6,830 community-dwelling elderly persons .  Cognitive performance ( global cognitive functioning , visual memory , verbal fluency , psychomotor speed , and executive function ) , clinical diagnosis of dementia , and fibrate and statin use , were evaluated at baseline , and 2 , 4 , and 7 year follow-up . Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics , mental and physical health including vascular risk factors , and genetic vulnerability ( apolipoprotein E and cholesteryl ester transfer protein ) . For women but not men , fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only ( HR = 1.29 , 95 % CI = 1.09 - 1.54 , p = 0.004 ) , and did not increase risk for incident dementia . This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate ( HR = 1.39 , 95 % CI = 1.08 - 1.79 , p = 0.01 ) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment . For both genders , no significant associations were found between statins ( irrespective of their lipophilicity ) and either cognitive decline or dementia incidence . This prospect i ve study , adjusting for multiple confounders , found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia , but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory OBJECTIVE To compare the effects of short-term and long-term thromboprophylaxis after total hip replacement on coagulation indicators in plasma sample d before and 1 , 7 and 35 days post-operation . METHODS A total of 40 patients scheduled for elective total hip replacement were r and omly assigned into the short-term ( n = 20 ) or long-term ( n = 20 ) thromboprophylaxis groups on oral rivaroxaban 10 mg once daily for 7 or 35 days . The primary efficacy hemostatic variables included thrombin-antithrombin complexes ( TAT ) , prothrombin fragment 1 + 2 ( F1t2 ) , D-dimer and fibrinogen ( Fib ) preoperatively and at Days 1 , 7 and 35 postoperatively . And ultrasonography was performed on all patients preoperatively and at days 7 and 35 postoperatively to exclude deep vein thrombosis of lower extremities . RESULTS None of them had deep vein thrombosis ( DVT ) of lower extremities . Among them , TAT , F1 + 2 , D-dimer and Fib post-operation were higher than those preoperative baseline values . TAT and D-dimer peaked at day 1 postoperatively while the peaks of F1 + 2 and Fib appeared at day 7 postoperatively . At Day 35 post-operation , the levels of TAT and F1 + 2 in the long-term thromboprophylaxis group were significantly lower than those of the short-term thromboprophylaxis group ( P < 0.05 ) . CONCLUSION The status of hypercoagulability may sustain at least 35 days after total hip replacement . Though not completely eliminated , it can still be reduced by prolonged thromboprophylaxis . However , according to ultrasonography , the effects of short-term and long-term thromboprophylaxis on the incidence rate of DVT remain to be further explored Abstract . Objectives : In patients with mixed lipid disorders , monotherapy may not effectively control all lipid abnormalities . We undertook this study to assess the efficacy of fenofibrate in combination with atorvastatin in patients with severe mixed dyslipidemia . Methods : This was an 18-week , open-label study conducted in our lipid clinic . After a 6-week dietary baseline phase , patients received 200 mg/day micronised fenofibrate for 6 weeks . At the end of this period the subjects discontinued this treatment and received 40 mg/day atorvastatin for 6 weeks . Finally 200 mg/day of micronised fenofibrate was added to the statin therapy . Results : Administration of micronised fenofibrate reduced serum triglycerides ( P<0.01 ) and total cholesterol and low-density lipoprotein ( LDL ) cholesterol ( P<0.05 for both parameters ) , while it evoked a significant increase in serum high-density lipoprotein ( HDL ) cholesterol levels ( P<0.05 ) . Atorvastatin monotherapy induced a more pronounced decrease of total and LDL cholesterol . However , plasma triglycerides , although significantly lower than baseline values ( P<0.05 ) , were higher than the values observed during treatment with fenofibrate . Moreover , serum HDL cholesterol concentrations were higher during fibrate therapy than during the statin one . During the combination therapy , the decrease in triglycerides was greater than that observed with fenofibrate alone , while the decrease in LDL cholesterol was more pronounced than that observed with atorvastatin alone . Conclusion : The combination of atorvastatin with micronised fenofibrate in patients with severe mixed dyslipidemia may have a favourable effect on some major coronary artery disease risk factors STUDY OBJECTIVE To determine if the use of statins affects pneumonia-related outpatient visits , hospitalizations with survival , and deaths . DESIGN Population -based , retrospective , nested case-control analysis . DATA SOURCE United Kingdom-based General Practice Research Data base . PARTICIPANTS The study population ( 134,262 patients aged > or = 30 yrs ) consisted of 55,118 patients who took statins and /or fibrates , 29,144 patients with hyperlipidemia not taking lipid-lowering agents , and 50,000 r and omly selected patients without hyperlipidemia and without lipid-lowering treatment .  MEASUREMENTS AND MAIN RESULTS We identified 1253 patients with pneumonia and matched them with 4838 control subjects based on age , sex , general practice , and index date . After adjusting for comorbidity and frequency of visits to general practitioners , we calculated the risks ( odds ratios with 95 % confidence intervals ) of uncomplicated pneumonia , hospitalization for pneumonia with survival , and fatal pneumonia in participants who used  statins compared with those who did not . Current statin users had a significantly reduced risk of fatal pneumonia ( adjusted odds ratio 0.47 , 95 % confidence interval 0.25 - 0.88 ) and slightly but not significantly reduced risks of uncomplicated pneumonia and pneumonia hospitalization with survival . Recent or past statin use and fibrate use at any time were not associated with a reduced risk of pneumonia . CONCLUSION Current use of statins was associated with a reduced risk of pneumonia . The risk reduction was particularly strong in the subgroup of patients with fatal pneumonias This study aim ed to compare the effects of ω-3 fatty acids and fibrate treatment on plasma levels and activities of hemostatic risk factors on glucose and lipid metabolism in subjects with isolated hypertriglyceridemia . Seventy-three subjects with elevated triglyceride levels were allocated into one of the following treatment options : bezafibrate ( 200 mg twice daily ) , ω-3 fatty acids ( 1 g twice daily ) or placebo . Plasma lipids , glucose homeostasis markers ( fasting and 2-h post-glucose load plasma glucose levels and HOMA ) , as well as plasma levels/activities of fibrinogen , factor VII and PAI-1 were determined at baseline , on the day of r and omization , and after 4 and 12 weeks of the treatment . Not only did bezafibrate  improve plasma lipids , but it also increased glucose sensitivity and tended to reduce post-glucose loads of plasma glucose . Except for the reduction in plasma triglycerides , ω-3 fatty acids produced no effect on the lipid profile and insulin sensitivity . Both treatment options reduced , to similar extents , plasma levels of fibrinogen and PAI-1 and factor VII coagulant activity . Our study indicates that , although fibrates exhibit more-pronounced metabolic effects than do ω-3 fatty acids , both these treatment options are equipotent in producing a complex beneficial effect on hemostasis in isolated hypertriglyceridemic subjects An elevated plasma fibrinogen level is increasingly accepted as an independent risk indicator of cardiovascular disease . This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels . One group of agents with this capacity are the fibric acid derivatives , e.g. ciprofibrate and gemfibrozil . We studied fibrinogen levels after 12 weeks of treatment with ciprofibrate  ( n = 48 ) and gemfibrozil  ( n = 51 ) in hypercholesterolenic patients . The correlation of the decrease in fibrinogen with lipid lowering and the contribution of the acute phase and genetic polymorphisms to this decrease were also evaluated . After 12 weeks of treatment , the fibrinogen levels were significantly decreased ( p < 0.0005 ) with both drugs , although the decrease in the ciprofibrate group ( mean 3.4 g/l pre-treatment to 2.4 g/l after 12 weeks ) was larger than in the gemfibrozil group ( mean 3.4 g/l to 3.0 g/l ) . The lipid lowering effect was comparable for the two drugs but there was no correlation for either ciprofibrate or gemfibrozil between the lipid lowering and the magnitude or the velocity of the fibrinogen lowering effect . An attenuation of the major regulatory mechanism of plasma fibrinogen levels , the acute phase reaction , was invoked as the underlying mechanism . However , pre-treatment C-reactive protein levels were not increased and did not change after treatment . Moreover , no effects of the polymorphisms of the fibrinogen beta-gene on the decrease of the plasma fibrinogen levels were observed . This suggests that a new , as yet unknown , mechanism is involved in fibrinogen lowering by fibrates
Monotherapy with either fibrates or statins suggested a significantly greater effect of fibrates in lowering plasma Fib concentrations .
According to these findings , mechanisms associated with fibrinogen metabolism might be responsible for the distinct effects of statins and fibrates in reducing cardiovascular endpoints
BACKGROUND Several studies suggest differences between fibrates and statins in lowering plasma fibrinogen ( Fib ) concentrations , but the evidence is not definitive .
Therefore , the aim of this meta- analysis of head-to-head r and omized trials was to compare the efficacy of statins and fibrates on plasma Fib concentrations .