title: Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Determinants of Variable Response to Statin Treatment in Patients With Refractory Familial Hypercholesterolemia Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial--FAT). Efficacy of combination of atorvastatin and micronised fenofibrate in the treatment of severe mixed hyperlipidemia Modulation of plasma fibrinogen levels by ciprofibrate and gemfibrozil in primary hyperlipidaemia. 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. Hemorheologic and Coagulative Pattern in Hypercholesterolemic Subjects Treated with Lipid-Lowering Drugs Statin therapy and levels of hemostatic factors in a healthy population: the Multi-Ethnic Study of Atherosclerosis. Effects of atorvastatin 10 mg and fenofibrate 200 mg on the low-density lipoprotein profile in dyslipidemic patients: A 12-week, multicenter, randomized, open-label, parallel-group study. Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular low-density lipoprotein immunoadsorption apheresis. The Effect of Atorvastatin on Serum Lipids, Lipoprotein(a) and Plasma Fibrinogen Levels in Primary Dyslipidaemia – A Pilot Study Involving Serial Sampling Comparison of bezafibrate and simvastatin in the treatment of dyslipidaemia in patients with NIDDM. Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients. A randomized pilot trial of low‐dose combination lipid‐lowering therapy following coronary artery bypass grafting Atherogenic risk reduction in patients with dyslipidaemia. comparison between bezafibrate and lovastatin. Effects of gemfibrozil on insulin sensitivity and on haemostatic variables in hypertriglyceridemic patients. Effects of fluvastatin and bezafibrate combination on plasma fibrinogen, t-plasminogen activator inhibitor and C reactive protein levels in coronary artery disease patients with mixed hyperlipidaemia (FACT study). Fluvastatin Alone and in Combination Treatment. Effects of atorvastatin versus fenofibrate on lipoprotein profiles, low-density lipoprotein subfraction distribution, and hemorheologic parameters in type 2 diabetes mellitus with mixed hyperlipoproteinemia. Beneficial effects of the addition of fenofibrate to statin therapy in patients with acute coronary syndrome after percutaneous coronary interventions. Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study. Combined bezafibrate and simvastatin treatment for mixed hyperlipidaemia. Comparison of bezafibrate versus lovastatin for lowering plasma insulin, fibrinogen, and plasminogen activator inhibitor-1 concentrations in hyperlipemic heart transplant patients. The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia. Effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen in hyperlipidaemic patients. Gemfibrozil reduces thrombin generation in patients with combined hyperlipidaemia, without influencing plasma fibrinogen, fibrin gel structure or coagulation factor VII. Effects of simvastatin and ciprofibrate alone and in combination on lipid profile, plasma fibrinogen and low density lipoprotein particle structure and distribution in patients with familial combined hyperlipidaemia and coronary artery disease Multicenter comparison of micronized fenofibrate and simvastatin in patients with primary type IIA or IIB hyperlipoproteinemia. The peroxisome proliferator-activated receptor alpha agonist fenofibrate has no effect on insulin sensitivity compared to atorvastatin in type 2 diabetes mellitus; a randomised, double-blind controlled trial.
abstract: OBJECTIVE This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile , in comparison to each drug alone , in patients with type 2 diabetes and combined hyperlipidemia ( CHL ) . RESEARCH DESIGN AND METHODS A total of 120 consecutive patients , who were free of coronary artery disease ( CAD ) at entry , were studied for a period of 24 weeks . These patients were r and omly assigned to atorvastatin ( 20 mg/day , n = 40 ) , micronized fenofibrate ( 200 mg/day , n = 40 ) , or a combination of both ( atorvastatin 20 mg/day plus fenofibrate 200 mg/day , n = 40 ) . The effect of treatment on LDL cholesterol , triglycerides ( TGs ) , HDL cholesterol , apolipoprotein A-I and B , lipoprotein(a ) , and plasma fibrinogen ( PF ) was recorded . Moreover , the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated . RESULTS No patient was withdrawn from the study because of side effects . The atorvastatin-fenofibrate combination reduced total cholesterol by 37 % , LDL cholesterol by 46 % , TGs by 50 % , and PF by 20 % , whereas it increased HDL cholesterol by 22 % ( P < 0.0001 for all ) . These changes were significantly better than those of both monotherapies . Of the patients on drug combination , 97.5 % reached the LDL cholesterol treatment goal of < 100 mg/dl , 100 % reached the desirable TG levels of < 200 mg/dl , and 60 % reached the optimal HDL cholesterol levels of > 45 mg/dl . These rates were significantly higher than those of both monotherapies . Combined treatment reduced the 10-year probability for myocardial infa rct ion from 21.6 to 4.2 % . CONCLUSIONS The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL . It improved patients ' CAD risk status significantly more than each drug alone Abstract —Interindividual variability in low density lipoprotein ( LDL ) cholesterol ( LDL-C ) response during treatment with statins is well documented but poorly understood . To investigate potential metabolic and genetic determinants of statin responsiveness , 19 patients with refractory heterozygous familial hypercholesterolemia were sequentially treated with placebo , atorvastatin ( 10 mg/d ) , bile acid sequestrant , and the 2 combined , each for 4 weeks . Levels of LDL-C , mevalonic acid ( MVA ) , 7-&agr;-OH-4-cholesten-3-one , and leukocyte LDL receptor and hydroxymethylglutaryl coenzyme A reductase mRNA were determined after each treatment period . Atorvastatin ( 10 mg/d ) reduced LDL-C by an overall mean of 32.5 % . Above-average responders ( & Dgr;LDL-C −39.5 % ) had higher basal MVA levels ( 34.4±6.1 & mgr;mol/L ) than did below-average responders ( & Dgr;LDL-C −23.6 % , P < 0.02 ; basal MVA 26.3±6.1 & mgr;mol/L , P < 0.01 ) . Fewer good responders compared with the poor responders had an apolipoprotein E4 allele ( 3 of 11 versus 6 of 8 , respectively;P < 0.05 ) . There were no baseline differences between them in 7-&agr;-OH-4-cholesten-3-one , hydroxymethylglutaryl coenzyme A reductase mRNA , or LDL receptor mRNA , but the latter increased in the good responders on combination therapy ( P < 0.05 ) . Severe mutations were not more common in poor than in good responders . We conclude that poor responders to statins have a low basal rate of cholesterol synthesis that may be secondary to a genetically determined increase in cholesterol absorption , possibly mediated by apolipoprotein E4 . If so , statin responsiveness could be enhanced by reducing dietary cholesterol intake or inhibiting absorption OBJECTIVE It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia . Studies assessing the effects of fibrates on endothelium have been neglected . Therefore , we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia . METHODS 29 otherwise healthy males ( aged 47.4+/-7.8 years ) with combined hyperlipidaemia ( total cholesterol 7.55+/-1.20 mmol/l , triglycerides 5.41+/-4.54 mmol/l ) were included into the r and omised , single-blind , cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily -- each of the drugs for a period of 10 weeks . Analysed biochemical parameters were as follows : serum total- , LDL- and HDL-cholesterol , apolipoproteins A-I and B , triglycerides , fibrinogen , uric acid , C-reactive protein ( CRP ) , insulin , and homocysteine . Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery . Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow ( PBF ) representing the level of reactive hyperaemia and traditional flow-mediated dilatation ( FMD ) . RESULTS We observed a small improvement in FMD after both fenofibrate and atorvastatin ( from 2.26 % to 2.98 % and 2.87 % , respectively ; NS ) . PBF increased from 448 ml/min to 536 ml/min after fenofibrate ( P=0.04 ) and to 570 ml/min after atorvastatin ( P=0.03 ) . The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly ( P-values of 0.82 and 0.47 for FMD and PBF , respectively ) . Significant correlations ( P<0.01 ) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP ( r=-0.60 ) and between both FMD and PBF , and insulinaemia ( r=-0.48 and -0.56 , respectively ) only during treatment with fenofibrate . CONCLUSIONS Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference . The PBF was superior to FMD for the detection of this improvement . The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy . The improvement of vascular reactivity during treatment with fenofibrate ( opposed to atorvastatin ) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance . The PBF was more reproducible than FMD because of considerably lower intra-subject variability 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 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 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 The effects on the coagulative and rheologic pattern of two lipid-lowering drugs , bezafibrate and simvastatin , were studied in 36 hypercholesterolemic subjects . Patients were r and omly divided into two groups ( 18 subjects each ) and received bezafibrate R 400 mg/day or simvastatin 10 - 40 mg/day over a twelve week period . Besides a decrease in plasma fibrinogen and fibrinopeptide A ( p<0.001 both ) , bezafibrate induced a reduction of factor VIIc and VIIIc activity ( p<0.001 both ) , while antithrombin 3 activity was increased ( p<0.001 ) and the hemorheologic pattern was greatly improved ( p<0.001 ) . Simvastatin caused a slight decrease in factor VIIIc activity and a moderate reduction of beta thromboglobulin . The efficacy of bezafibrate in reducing the activation of the coagulative cascade and improving the hemorheologic pattern has been con firmed ; the peculiar triglycerides- and fibrinogen-lowering effect of the drug , not observed with simvastatin , could be responsible for these modifications BACKGROUND HMG-CoA reductase inhibitors ( statins ) reduce the risk of venous thromboembolism ( VTE ) in healthy people .  Statins reduce levels of inflammation biomarkers ; however , the mechanism for the reduction in VTE risk is unknown . AIM In a large cohort of healthy people , we studied associations of statin use with plasma hemostatic factors related to VTE risk . METHODS Cross-sectional analyses were performed in the Multi-Ethnic Study of Atherosclerosis ( MESA ) , a cohort study of 6814 healthy men and women aged 45 - 84 years , free of clinical cardiovascular disease at baseline ; 1001 were using statins at baseline . Twenty-three warfarin users were excluded . Age , race and sex-adjusted mean hemostatic factor levels were compared between statin users and non-users , and multivariable linear regression models were used to assess associations of statin use with hemostatic factors , adjusted for age , race/ethnicity , education , income , aspirin use , hormone replacement therapy ( in women ) , and major cardiovascular risk factors . RESULTS Participants using statins  had lower adjusted levels of D-dimer ( - 9 % ) , C-reactive protein ( - 21 % ) and factor VIII ( - 3 % ) than non-users ( P < 0.05 ) . Homocysteine and von Willebr and factor levels were non-significantly lower with statin use . Higher fibrinogen ( 2 % ) and plasminogen activator inhibitor-1 ( 22 % ) levels were observed among statin users than among non-users ( P < 0.05 ) . Further adjustment for LDL and triglyceride levels did not attenuate the observed differences in these factors with statin use . CONCLUSIONS Findings of lower D-dimer , FVIII and C-reactive protein levels with statin use suggest hypotheses for mechanisms whereby statins might lower VTE risk . A prospect i ve study or clinical trial linking these biochemical differences to VTE outcomes in  statin users and non-users is warranted BACKGROUND Elevated plasma low-density lipoprotein cholesterol ( LDL-C ) concentrations are highly atherogenic , especially the small , dense LDL ( sdLDL ) species . Fenofibrate has been reported to shift the LDL profile by decreasing the sdLDL subfraction and increasing larger LDL subclasses . Atorvastatin , anantihyperlipidemic agent , has been reported to reduce plasma total cholesterol ( TC ) and triglyceride ( TG ) concentrations and thus could modify the LDL profile . OBJECTIVE The aim of this study was to compare the effects of fenofi brate and atorvastatin on st and ard lipid concentrations and the LDL profile . METHODS In this r and omized , open-label , parallel-group study , men and women aged 18 to 79 years with type II primary dyslipidemia , defined as LDL-C ≥160 and TG 150 to 400 mg/dL , after a 4- to 6-week washout period while eating an appropriate diet , were r and omized to receive either atorvastatin 10 mg once daily or fenofi-brate 200 mg once daily  . Plasma lipid concentrations and cholesterol and apolipoprotein ( apo ) B ( reflecting the LDL particle number ) in each LDL subfraction prepared by ultracentrifiigation were determined at baseline and after 12 weeks of treatment . Tolerability was assessed using adverse events ( AEs ) obtained on laboratory analysis and vital sign measurement . Adherence was assessed by counting unused drug supplies . RESULTS A total of 165 patients ( 117 men , 48 women ; mean [ SD ] age , 50.1 [ 10.7 ] years ; mean TC concentration , 289 mg/dL ) were r and omized to receive atorvastatin ( n = 81 ) or fenofibrate ( n = 84 ) . Compared with fenofibrate , atorvastatin was associated with a significantly greater mean ( SD ) percentage decrease in TC ( 27.0 % [ 12.3 % ] vs 16.5 % [ 12.9 % ] ; P < 0.001 ) , calculated LDL-C ( 35.4 % [ 15.8 % ] vs 17.3 % [ 17.2 % ] ; P < 0.001 ) , TC/high-density lipoprotein cholesterol ( HDL-C ) ratio ( 29.1 % [ 16.3 % ] vs 22.9 % [ 15.9 % ] ; P = 0.001 ) , and apoB ( 30.3 % [ 12.7 % ] vs 19.6 % [ 15.5 % ] ; P < 0.001 ) . Compared with atorvastatin , fenofibrate was associated with a significantly greater decrease in TG ( 37.2 % [ 25.9 % ] vs 20.2 % [ 27.3 % ] ; P < 0.001 ) and a significantly greater increase in HDL-C concentration ( 10.4 % [ 15.7 % ] vs 4.6 % [ 12.1 % ] ; P = 0.017 ) . Fibrinogen concentration was significantly different between the 2 groups ( P = 0.002 ) ; it was decreased with fenofibrate use ( 4.6 % [ 23.7 % ] ) and was increased with atorvastatin use ( 5.7 % [ 23.5 % ] ) . Atorvastatin did not markedly affect the LDL distribution ; it was associated with a homogeneous decrease in cholesterol and apoB concentrations in all subfractions , whereas fenofibrate was associated with a marked movement toward a normalized LDL profile , shifting the sdLDL subfractions toward larger and less atherogenic particles , particularly in those patients with baseline TG ≥200 mg/dL. No serious AEs related to the study treatments were reported . A total of 5 AEs were observed in 8 patients , including : abdominal pain , 3 patients ( 2 in the atorvastatin group and 1 in the fenofibrate group ) ; abnormal liver function test results , 1 ( fenofibrate )  ; increased creatine Phosphokinase activity , 2 ( atorvastatin )  ; gastrointestinal disorders , 1 ( fenofibrate ) ; and vertigo , 1 ( fenofibrate ) . CONCLUSION In these dyslipidemic patients  , fenofibrate treatment was associated with an improved LDL subfraction profile beyond reduction in LDL-C , particularly in patients with elevated TG concentration , whereas atorvastatin was associated with equally reduced concentrations of cholesterol and apoB in all LDL subfractions independent of TG concentrations Low-density lipoprotein ( LDL ) apheresis is a treatment option in patients with coronary artery disease and elevated LDL cholesterol concentrations if maximal drug therapy fails to achieve adequate LDL cholesterol reduction . This therapy is more effective when combined with strong lipid-lowering drugs , such as atorvastatin . However , conflicting data have been published concerning the effect of atorvastatin on fibrinogen concentration . Therefore , we investigated the effect of atorvastatin compared to simvastatin on fibrinogen concentration and other hemorheological parameters in patients treated by weekly LDL apheresis .  Hemorheological parameters were , studied twice in 9 patients ( 4 female , 5 male , 54.0+/-8.9 years ) with coronary artery disease treated by weekly LDL immunoadsorption , once during concomitant simvastatin therapy ( 40 mg daily ) and once during atorvastatin therapy ( 40 mg daily ) .  Fibrinogen concentration , plasma and blood viscosity at different shear rates , parameters of red cell aggregation at stasis and shear rate 3/s , and erythrocyte filterability were determined 7 days after the last LDL apheresis after each drug had been given for a minimum for 8 weeks . Fibrinogen concentration did not show any statistically significant difference during therapy with atorvastatin ( 3.09+/-0.36 g/L ) compared to simvastatin ( 3.13+/-0.77 g/L ) . Plasma and blood viscosity as well as erythrocyte filterability were also unchanged . The increase in red cell aggregation at stasis during atorvastatin treatment ( 5.82+/-1.00 U versus 4.89+/-0.48 U during simvastatin ; p < 0.05 ) was inversely correlated with a lower high-density liprotein ( HDL ) cholesterol concentration ( 1.17+/-0.21 mmol/L versus 1.31+/-0.30 mmol/L during simvastatin ; p < 0.05 ) . LDL cholesterol showed a strong trend to lower concentrations during atorvastatin ( 4.14+/-0.61 mmol/L versus 4.56+/-0.66 mmol/L during simvastatin ; p = 0.07 ) , despite a reduced plasma volume treated ( 3,547+/-1,239 ml during atorvastatin versus 3,888+/-1,206 mL during simvastatin ; p < 0.05 ) . In conclusion , fibrinogen concentration and other hemorheological parameters were unchanged during atorvastatin compared to simvastatin therapy with the exception of a higher red cell aggregation at stasis . Therefore , with respect to hemorheology , we conclude that atorvastatin should not be withheld from hypercholesterolemic patients regularly treated with LDL immunoadsorption Summary We conducted an open-label study to test the effects of atorvastatin on serum lipids , lipoprotein(a ) [ Lp(a ) ] and plasma fibrinogen levels .  A total of 90 dyslipidaemic , nonsmoking patients ( 45 patients with primary hypercholesterolaemia and 45 patients with primary mixed hyperlipidaemia ) aged 48 ± 11 years were studied . The patients were treated with 20 mg of atorvastatin for 24 weeks , in a single nocturnal dose . At baseline and every eight weeks , the fasting lipid profile , together with serum Lp(a ) and plasma fibrinogen levels ( Clauss method ) , were measured . Atorvastatin was highly effective in normalising the serum lipid profile . No significant change in median serum Lp(a ) levels was observed in the whole group of patients ( 0.14 g/l before , vs. 0.16 g/l after , treatment ) as well as in patients with raised ( > 0.30 g/l ) baseline levels ( n = 32 ) . A small non-significant increase of plasma fibrinogen was found ( 3.04 g/l vs. 3.14 g/l ) after 24 weeks of atorvastatin administration . The effects of atorvastatin on both these variables did not differ in patients with hypercholesterolaemia or mixed hyperlipidaemia . In conclusion , our findings suggest that the effect of atorvastatin  on plasma fibrinogen levels in dyslipidaemic patients without evident vascular disease is not clinical ly relevant . Furthermore , any rise in fibrinogen levels that may occur is likely to be transient in nature . Further studies are necessary to clarify this issue . There was no evidence that atorvastatin  influences serum Lp(a ) levels Fibrates and HMG CoA reductase inhibitors are commonly used in the treatment of diabetic dyslipidaemia . However , these two groups of drugs have not been compared in diabetic patients in a r and omized controlled trial . Therefore , a multicentre study was performed in 73 subjects with non-insulin-dependent ( Type 2 ) diabetes mellitus ( NIDDM ) and combined hyperlipidaemia ( serum cholesterol 6.2 - 10.0 mmol l(-1 ) , serum triglycerides 2.3 - 10.0 mmol l(-1 ) ) , comparing the efficacy of 400 mg bezafibrate with 10 mg simvastatin in a double-blind fashion . Treatment with bezafibrate during 12 weeks reduced serum triglycerides significantly more than simvastatin ( -41 % vs -22 % , p < 0.001 ) and increased HDL cholesterol more ( bezafibrate : + 17 % vs simvastatin : + 9 % , p < 0.05 ) . LDL cholesterol levels decreased by 14 % ( p < 0.001 ) during simvastatin and increased by 21 % ( p < 0.01 ) during bezafibrate . This increase in LDL cholesterol was positively correlated with fasting serum triglycerides ( p < 0.001 ) and was associated with a reduction of the serum apolipoprotein B concentration , suggesting an increase in LDL particle size . Metabolic control of diabetes ( fasting glycaemia ; HbA1c ) and insulin secretion ( C-peptide levels ) were unaffected by both treatments . The incidence of side-effects during treatment was similar for both drugs . Thus , 400 mg bezafibrate mainly increases HDL cholesterol and lowers serum triglycerides but at the expense of an increase in LDL cholesterol ; 10 mg simvastatin lowers LDL cholesterin more effectively but has a smaller effect on HDL cholesterol and triglycerides Previous studies suggested that certain lipid-lowering drugs such as statins suppress ubiquinone , affect mitochondrial function , and may have deleterious effect on skeletal or cardiac muscles with potentially serious clinical consequences , especially in patients with established coronary heart disease and left ventricular dysfunction . In this double-blind study , we assessed the effects of 20 mg simvastatin ( S , n = 32 ) or 200 mg micronized fenofibrate ( F  , n = 32 ,  control group ) on rest and exercise left ventricular function in hypercholesterolemic survivors of a previous Q-wave acute myocardial infa rct ion . Left ventricular radionuclide imaging was performed at rest and during submaximal exercise and global and segmental ( nine segment regional wall-motion score ) ejection fractions were measured before treatment and 12 weeks later . Serum ubiquinone was reduced after treatment ( p = 0.03 ) in the S but not the F group , whereas total and low-density lipoprotein ( LDL ) cholesterol were significantly reduced in both groups . Before treatment , mean global ejection fraction was 52.1+/-12.2 % and 49.3+/-11.8 % at rest in F and S patients , respectively , and increased ( 56.0+/-13.7 % in F and 52.1+/-12.9 % in S ) at peak exercise ( no difference between groups ) . After treatment , the increase in ejection fraction tended to be lower in S ( 0 ) than in F ( + 3.8 % ) but not significantly . However , ejection fraction at rest increased after treatment in S ( p = 0.009 ) but not in F. Subgroup analyses indicated that the improvement in rest ejection fraction in S was essentially observed in patients with ejection fraction < 40 % ( n = 8 , + 6 % ) , whereas it was stable in patients with ejection fraction > 40 % ( + 1.8 % ) . Finally , the numbers of akinetic or hypokinetic segments at rest and during exercise were not different in the two groups before and after treatment . Mean maximal exercise load ( 113+/-23 watts in F vs. 104+/-27 W in S before treatment ) was not modified by the treatment ( 111+/-21 and 104+/-27 W ) . Thus a 12-week lipid-lowering treatment with either S or F did not negatively alter left ventricular function during exercise in dyslipidemic patients with established coronary heart disease and did not affect their ability to exercise . The improvement in left ventricular function at rest after simvastatin in patients with left ventricular dysfunction warrants confirmation in further studies with large sample size Vein graft atherosclerosis is a common and serious complication of coronary artery bypass grafting ( CABG ) . There is mounting evidence that lipoprotein abnormalities play an equally important role in the development of lesions in saphenous vein grafts after CABG as in native coronary vessel disease . The potential benefit of low‐dose lipid lowering combination therapy in these patients has not been investigated . In a r and omized , double‐blind , placebo‐controlled study , we compared the efficacy and safety of a low‐dose combination of colestipol 10 g and simvastatin 10 mg/day ( CS ) to colestipol 10 mg and bezafibrate 400 mg/day ( CB ) for 2 months in 33 patients with serum total cholesterol > 6.5 mmol/l and triglyceride < 4.5 mmol/l who had undergone CABG for severe coronary artery disease . In the CS group , total cholesterol decreased by 29 % and low‐density lipoprotein ( LDL ) cholesterol by 42 % ; similarly , CB reduced total cholesterol by 17 % , LDL cholesterol by 23 % , triglyceride by 19 % , and increased high‐density lipoprotein ( HDL ) cholesterol by 14 % . Lipoprotein ( a ) and hemostatic factors were unaffected by either therapy in this study . Both combination therapies were well tolerated with no significant clinical or biochemical side effects . We conclude that low‐dose combinations of colestipol and simvastatin or colestipol and bezafibrate are effective and well tolerated in the management of moderate hyperlipidemia in patients who had undergone CABG OBJECTIVE To examine the atherogenic risk-reducing effect of bezafibrate and lovastatin . DESIGN , SETTING , PATIENTS , INTERVENTIONS Double-blind , r and omized clinical trial of male and female patients with moderate hypercholesterolaemia with or without hypertriglyceridaemia . Two months dietary treatment followed by 400 mg sustained release bezafibrate every day or 20 mg lovastatin every day for 6 months . Patients recruited ( n = 561 ) and treated ( n = 524 ) by primary care physicians throughout Austria . MAIN OUTCOME MEASURES Multifactorial assessment of atherogenic risk profile . RESULTS Bezafibrate increased high density lipoprotein cholesterol by 16 % , lovastatin by 10 % ( P < 0.05 ) . Bezafibrate decreased low density lipoprotein cholesterol by 20 % , lovastatin by 27 % ( P < 0.001 ) . Bezafibrate decreased total cholesterol by 15 % , lovastatin by 18 % ( P < 0.001 ) . Bezafibrate reduced triglycerides by 29 % , lovastatin by 13 % ( P < 0.001 ) ; and fibrinogen by 9.4 % and 3.0 % , respectively . Fibrinogen reduction as a result of bezafibrate administration was dependent on starting levels . The risk ratio cholesterol : high density lipoprotein cholesterol ( baseline both 6.1 ) reduction was 27 % in both groups . The low : high density lipoprotein ratio ( baseline : 4.1/4.2 ) reduction reached 31 % and 34 % respectively . Coronary events ' probability ( calculated from multifactorial risk functions ) were greatly reduced by both agents ( 41%/33 % ) . Hypertriglyceridaemic patients had a higher initial global coronary risk and profited more from treatment . Bezafibrate was significantly better tolerated ( P < 0.001 ) than lovastatin ; most events were gastrointestinal ( 6 vs 14 , ns ) or as a result of creatine phosphokinase elevations ( 3 vs 12 , P < 0.05 ) . CONCLUSIONS Both treatments significantly reduced the risk parameters for developing coronary heart disease , and calculated multifactorial coronary risk was similarly decreased . When selecting a drug for moderate dyslipidaemia and if haemostatic regulation is disturbed , the additional effect of bezafibrate on elevated fibrinogen levels should be considered In order to assess the efficacy of gemfibrozil on lipid and haemostatic parameters in patients with plurimetabolic syndrome , a multicenter double-blind placebo controlled , parallel study was carried out in 56 patients with primary hypertriglyceridemia and glucose intolerance . These patients had elevated PAI activity and antigen and t-PA antigen levels at rest and after venous occlusion . Gemfibrozil reduced plasma triglyceride levels ( P<0.001 ) , whereas it increased free fatty acids ( P<0.05 ) and high density lipoprotein cholesterol levels ( P<0.05 ) . In those patients reaching normalization of plasma triglyceride levels ( triglyceride reduction > or = 50 % ) ( n=15 ) , insulin levels ( P<0.05 ) as well as the insulin resistance index were reduced by gemfibrozil treatment , suggesting an improvement of the insulin resistance index in this patient subgroup . Gemfibrozil treatment did not affect plasma fibrinolysis or fibrinogen levels , despite marked reduction of plasma triglycerides and improvement of the insulin sensitivity associated with triglyceride normalization AIM OF THE STUDY We studied the effects of fluvastatin and bezafibrate in monotherapy and in combination on plasma fibrinogen , t-plasminogen activator inhibitor ( PAI-1 ) and C reactive protein ( CRP ) in patients with coronary artery disease ( CAD ) and mixed hyperlipidaemia . DESIGN In this r and omised , double blind , multicentre trial 333 patients with stable angina pectoris or previous myocardial infa rct ion or coronary revascularisation and mixed hyperlipidaemia ( LDL-cholesterol 135 - 250 mg/dl and triglycerides ( TG ) 180 - 400 mg/dl ) were r and omised to fluvastatin 40 mg , bezafibrate 400 mg , fluvastatin 20 mg + bezafibrate 400 mg or fluvastatin 40 mg + bezafibrate 400 mg treatments for 24 weeks . RESULTS Plasma fibrinogen significantly decreased after treatment with the combinations fluvastatin+bezafibrate ( -14 and -16 % ) and with bezafibrate monotherapy ( -9 % ) . No significant reduction was observed after fluvastatin monotherapy ( -4 % ) . No significant changes were observed in PAI-1 and CRP plasma levels . Combination therapy significantly decreased both LDL-C and TG , and significantly increased HDL-C. CONCLUSIONS The combined effects on fibrinogen and plasma lipids achieved by fluvastatin and bezafibrate combination treatment might be more useful than the simple reduction of cholesterol in preventing ischaemic cardiovascular disease 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 OBJECTIVE To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors , especially plasma fibrinogen , in patients with acute coronary syndrome ( ACS ) requiring percutaneous coronary interventions . METHODS A r and omized , non-blinded , prospect i ve study with parallel group design . One hundred two ACS patients who underwent angioplasty were r and omly assigned to atorvastatin ( 20 mg/day , n=25 ) , simvastatin ( 40 mg/day , n=27 ) , atorvastatin-fenofibrate ( 10 mg/day-200 mg/day ) combination ( n=25 ) or simvastatin-fenofibrate ( 20 mg/day-200 mg/day ) combination ( n=25 ) . The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments . RESULTS All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines . The addition of fenofibrate to statin monotherapy produced further benefits to the reduction in triglyceride and very low-density lipoprotein levels , and caused an increase in high-density lipoprotein levels . All the treatment groups showed a significant decrease in the plasma fibrinogen levels . Plasma fibrinogen did not correlate with study parameters such as age , body weight , hemo-dynamic characteristics and lipoprotein levels . Statin monotherapy as well as its combination with fenofibrate produced a significant decrease in the fibrinogen levels . CONCLUSIONS The addition of fenofibrate to statins seems to be beneficial in patients with ACS . Statins decreased plasma fibrinogen significantly , contrary to results from various reports , and the addition of fenofibrate further enhanced this reduction of the novel risk factor fibrinogen BACKGROUND Coadministration of statin and fenofibrate monotherapies is frequently used to treat patients with dyslipidemia ; however , a fixed-dose combination ( FDC ) tablet is not currently marketed . OBJECTIVE This study evaluates a new FDC tablet of atorvastatin 40 mg and fenofibrate 100 mg . METHODS This was a 12-week , multicenter , double-blind , r and omized , parallel-group Phase IIb study . Adults with dyslipidemia ( non-HDL-C > 130 mg/dL and triglycerides [ TG ] > or = 150 but < or = 500 mg/dL ) were r and omly assigned in a 1:1:1 ratio to receive the FDC , atorvastatin 40 mg , or fenofibrate 145 mg for 12 weeks . Study medication was taken once daily in the evening , without regard to meals . Patients attended follow-up visits after 4 , 8 , and 12 weeks of the double-blind treatment . The primary efficacy end points were the mean percentage changes from baseline to the final visit ( week 12 ) in non-HDL-C , HDL-C , and TG . Secondary variables were LDL-C , VLDL-C particle concentration , total cholesterol , apolipoprotein B , lipoprotein ( a ) , high-sensitivity C-reactive protein , fibrinogen , homocysteine , creatinine , myeloperoxidase , and lipoprotein-associated phospholipase A2 . Tolerability was assessed by adverse events , laboratory parameters , vital signs , physical examinations , and ECGs . RESULTS Patients ( n = 220 ) were aged 26 to 87 years ; 115 ( 52.3 % ) were men and 105 ( 47.7 % ) were women ; 189 ( 85.9 % ) were white , 17 ( 7.7 % ) were black , and 15 ( 6.8 % ) were Hispanic or Latino ; and mean ( SD ) weight was 200.5 ( 40.85 ) lb ( range , 103.5 - 367.4 lb ) . Previous treatments were statins ( 25.9 % [ 57/220 ] ) , fibrates ( 1.8 % [ 4/220 ] ) , and dietary supplements ( 25.5 % [ 56/220 ] ) ; 57.7 % ( 127/220 ) of patients were treatment naive . Use of the FDC was associated with an improvement in non-HDL-C ( -44.8 % ) that was significantly greater than with fenofibrate monotherapy ( -16.1 % ; P < 0.001 ) but was not significantly different from that with atorvastatin monotherapy ( -40.2 % ; P = NS ) . HDL-C increased significantly more in the FDC group ( 19.7 % ) than with atorvastatin ( 6.5 % ; P < 0.001 ) but was not significantly different from fenofibrate ( 18.2 % ; P = NS ) . TG lowering in the FDC group ( -49.1 % ) was significantly greater than with both atorvastatin ( -28.9 % ; P < 0.001 ) and fenofibrate ( -27.8 % ; P = 0.001 ) . LDL-C lowering in the FDC group ( -42.3 % ) was significantly greater than with fenofibrate ( -13.9 % ; P < 0.001 ) but not significantly different from atorvastatin ( -43.1 % ; P = NS ) . The FDC had either comparable or significantly greater improvements in other lipid variables and multiple secondary variables . The FDC was generally well tolerated ; the tolerability profile was consistent with those of atorvastatin and fenofibrate monotherapies . Treatment-emergent adverse events ( ie , those occurring after the first dose of study medication ) were recorded in 43 of 73 patients ( 58.9 % ) for the FDC , 49 of 74 ( 66.2 % ) for atorvastatin , and 48 of 73 ( 65.8 % ) for fenofibrate . CONCLUSIONS In this 12-week study , patients with dyslipidemia treated with the 40/100-mg atorvastatin/ fenofibrate FDC had a significantly greater reduction in TG than those treated with atorvastatin 40 mg or higher-dose fenofibrate 145 mg . Treatment with the FDC was also associated with a significantly greater reduction in non-HDL-C compared with fenofibrate alone and a greater increase in HDL-C compared with atorvastatin alone . All treatments were generally well tolerated The safety and efficacy of combined bezafibrate-simvastatin therapy was evaluated in 49 patients with diet-resistant mixed hyperlipidaemia ( type IIb ) . After a two-month placebo phase , patients were r and omized to receive either Bezafibrate Slow Release ( SR ) 400 mg mane or simvastatin 20 mg nocte followed by three months combination therapy . Total cholesterol , triglycerides and high-density lipoprotein ( HDL ) cholesterol were measured at monthly intervals . Apolipoproteins ( apo ) A1 and B , lipoprotein ( a ) [ Lp(a ) ] and fibrinogen were measured before and after each treatment . Simvastatin was more effective than Bezafibrate SR in reducing total cholesterol ( 2.0 vs. 1.1 mmol/l , p = 0.003 ) and lowering LDL cholesterol ( 1.7 vs. 0.4 mmol/l , p = 0.0001 ) whereas Bezafibrate SR was more effective in reducing triglycerides ( by 41 % vs. 17 % , p = 0.001 ) and fibrinogen ( by 23 % vs. 3 % , p = 0.004 ) . Compared with simvastatin monotherapy , combined drug therapy induced further reductions in triglycerides ( by 26 % , p = 0.0003 ) and apoB ( by 11 mg/dl , p = 0.03 ) and an increase in apoA1 ( by 21 mg/dl , p = 0.0008 ) . Symptomatic and biochemical adverse events did not occur more frequently on combined drug therapy than on monotherapy . The combination of bezafibrate and simvastatin was more effective in controlling mixed hyperlipidaemia than either drug alone and did not provoke more adverse events Accelerated coronary artery disease is the most serious obstacle to long-term survival in heart transplant recipients . Hyperlipemia , hyperinsulinism , and changes in endothelial cell hemostatic function have been implicated in cardiac allograft vascular disease . Both lovastatin and bezafibrate are safe , effective , and well tolerated therapies for hyperlipidemia . Our study compares the effect of these lipid-lowering drugs in 21 patients with post-heart transplantation hyperlipidemia on different risk factors related to insulin resistance syndrome . Patients were given the same diet for 3 months , then r and omized to lovastatin or bezafibrate for a period of 8 weeks , and crossed over to an additional 8 weeks of either bezafibrate or lovastatin . Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment . Transplant patients had higher insulin ( 35 + /- 3 vs 24 + /- 3 microIU/L ) , fibrinogen ( 298 + /- 15 vs 261 + /- 14 mg/dl ) , and plasminogen activator inhibitor-1 ( PAI-1 ) ( 17 + /- 2 vs 11.7 + /- 2 arbitrary units/ml ) plasma levels than controls . Significant decreases in insulin ( -37 + /- 3 % ) , fibrinogen ( -12 + /- 4 % ) , and PAI-1 plasma levels ( -18 + /- 12 % ) were only observed after bezafibrate treatment . In conclusion , bezafibrate decreases plasma insulin , fibrinogen , and PAI-1 in hyperlipidemic heart transplant recipients Hyperlipidemia is an important risk factor for atherosclerosis . Hemorheological factors contribute to morbidity and mortality in patients with dyslipidemia . We evaluated the effects of 3 antihyperlipidemic drugs ( pravastatin , atorvastatin , and fenofibrate ) , which have different mechanisms of action and different patterns of action on lipid profiles , on erythrocyte deformability and fibrinogen levels in patients with type IIa and type IIb hyperlipidemia . Twenty-one patients ( 4 men and 17 women ) with type IIa and IIb hyperlipidemia were r and omized to 3 drugs ( pravastatin 20 mg/d , atorvastatin 10 mg/d , fenofibrate 250 mg/d ) for 8 weeks . Plasma glucose , total cholesterol , triglyceride , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) analysis were performed on a BM-Hitachi 747 - 200 autoanalyzer ( Hitachi-Roche , Tokyo , Japan ) . Fibrinogen analysis was performed according to Clauss method . Erythrocyte deformability was assessed with cell transit analysis device . There was no significant difference in body mass index , lipid profile , fibrinogen level , and erythrocyte deformability index values among the groups before treatment ( P > .05 ) . In all groups , there were statistically significant reductions in total LDL-C levels ( P < .05 ) . The triglyceride levels were significantly reduced in the atorvastatin and fenofibrate groups ( P < .05 ) , but not in the pravastatin group ( P > .05 ) . There was no significant change in HDL-C levels during the treatment with statins ( P > .05 ) , but there was a significant increase in the fenofibrate group ( P < .05 ) . Mean erythrocyte deformability index was improved in all the groups ( P < .05 ) . There was no significant change in fibrinogen levels during the treatment of pravastatin and atorvastatin ( P > .05 ) , but in fenofibrate group , fibrinogen levels were significantly decreased ( P < .05 ) . The 3 groups of antihyperlipidemic drugs have beneficial effects on the erythrocyte deformability index . Only fenofibrate has significant beneficial effects on the fibrinogen levels 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 A double-blind , placebo-controlled , cross-over study was conducted in 21 men with combined hyperlipoproteinaemia to examine if lipid-lowering treatment with gemfibrozil ( 10 - 12 weeks ) affects blood coagulation and fibrin gel structure at rest or during mental stress . Gemfibrozil lowered plasma triglycerides by 57 + /- 4 % , whereas high density lipoprotein ( HDL ) cholesterol increased by 22 + /- 5 % . Gemfibrozil lowered the triglyceride content of low density lipoprotein ( LDL ) . Gemfibrozil reduced the plasma concentrations of thrombin-antithrombin complex ( TAT ) and prothrombin fragment F1 + 2 ( F1 + 2 ) , both at rest and during mental stress . However , there were no effects of gemfibrozil treatment on the plasma concentrations of fibrinogen , factor VII antigen , activated factor VII ( VIIa ) or activated factor XII ( XIIa ) , or on fibrin gel structure . Acute mental stress per se did not influence coagulation factors , reaction products or fibrin gel structure , or their responses to the study drug . Thus , gemfibrozil reduced thrombin generation in men with combined hyperlipoproteinaemia , without influencing the plasma levels of fibrinogen , VIIa and XIIa , or fibrin gel structure . Attenuation of thrombin generation may contribute to the primary -preventive effects of gemfibrozil on coronary heart disease Background Hypolipidaemic agents do not usually normalize all of the multiple lipoprotein abnormalities in patients with familial combined hyperlipidaemia ( FCHL ) . The effect of the simvastatin-ciprofibrate combination in comparison with each drug alone on the lipoprotein abnormality patterns was studied in patients with FCHL and coronary artery disease ( CAD ) . Methods Sixty patients ( 53 men and seven women ) , mean age 52 years ( range 36–60 years ) , were studied . After a 4-week placebo period , patients were r and omly assigned to three groups . The first group ( n = 20 ) received simvastatin ( 20 mg daily ) , the second group ( n = 20 ) ciprofibrate ( 100 mg daily ) and the third group ( n = 20 ) the combination of both drugs for a 1 2-week period . Parameters measured were as follows : plasma fibrinogen , total cholesterol , triglycerides , low density lipoprotein ( LDL ) , very low density lipoprotein , intermediate density lipoprotein , and high density lipoprotein cholesterol , as well as LDL subfraction distribution and structure by density gradient ultracentrifugation . Apoproteins ( apo ) B and Al were assessed by immunoturbidometry . Results At baseline , apoB , LDL cholesterol and triglycerides were increased , whereas LDL particles were small and dense . ApoB was significantly reduced by all three interventions . Drug combination and ciprofibrate significantly reduced plasma fibrinogen ( -24 and −25 % , respectively ; P < 0.001 ) and triglycerides ( -51 and −49 % , respectively ; P < 0.001 ) . Drug combination and simvastatin significantly reduced LDL cholesterol ( -25 and −22 % , respectively ; P < 0.001 ) compared with ciprofibrate ( -10 % ; P<0.01 ) . Ciprofibrate and drug combination  increased LDL particle size ( parameter K −0.24 versus −0.61 and −0.30 versus −0.62 , respectively ; P < 0.001 ) , whereas simvastatin had no significant effect on LDL particle size . The cholesterol content of LDL particles was reduced with ciprofibrate and the drug combination only in the dense LDL particles ( LDL3–5 ) and increased in the light ( LDL1–2 ) subfractions , whereas simvastatin reduced the cholesterol content of all LDL subfractions except LDL2 . Ciprofibrate and drug combination reduced the triglyceride content of al ! LDL subfractions . Conclusion Combined treatment with simvastatin and ciprofibrate  effectively reduced plasma fibrinogen , triglycerides , total and LDL cholesterol and increased LDL particle size in patients with FCHL and CAD . These effects might induce a clinical benefit for these patients In 12 weeks of active treatment , we compared the efficacy and safety of a new ( micronized ) formulation of fenofibrate ( F ) ( 200 mg/day ) with that of simvastatin ( S ) ( 20 mg/day ) , an inhibitor of hydroxy-methyl-glutaryl coenzyme A (HMG-CoA)-reductase . Men and women with primary hyperlipoproteinemia ( HLP ) with low-density lipoprotein ( LDL ) cholesterol level 180 - 300 mg/dl and triglyceride level < 500 mg/dl had dietary treatment for 8 weeks , and 133 ( 2 of 3 type IIa , 1 of 3 type IIb HLP ) were r and omized . The decrease in total cholesterol differed between type IIa patients ( F - 17.9 vs. S - 25.8 % ) , the decrease in triglyceride levels between the type II b groups ( F - 52.8 vs. S - 14 % ) , whereas the degree of decrease in LDL cholesterol ( F - 20.9 vs. S - 34.9 % ) differed among all patients . Despite the difference in LDL cholesterol decrease , no difference was noted in total apolipoprotein ( apo ) B lowering ( F - 20.8 and S - 26.5 % ) . Increases in high-density lipoprotein ( HDL ) cholesterol ( F + 18.5 vs. S + 15 % ) differed specifically in type IIb patients ( F + 33.6 vs. S + 11.4 % ) , accompanied by a more pronounced increase in apo AI with fenofibrate ( F + 10.5 % vs. S no change ) . Improvement in the ratios of total cholesterol/HDL cholesterol and apo AI/apo B occurred similarly with both drugs . Only fenofibrate , not simvastatin , decreased both fibrinogen ( -10.3 vs. + 3.6 % ) and uric acid ( -25 % vs. no change ) in type IIa and type IIb patients . Safety parameters reflected drug-specific known side effects , underscoring the safety of both drugs in addition to their efficacy in lipid lowering . Besides its advantages in type IIb hyperlipidemia , micronized fenofibrate proved a potent drug in decreasing total and LDL cholesterol and in very effectively decreasing apo B-containing lipoproteins , which is a recommendation for its use in primary hypercholesterolemia AIMS Assess insulin sensitivity after treatment with a selective PPAR-alpha agonist compared to an HMG CoA reductase inhibitor in human subjects with type 2 diabetes mellitus . METHODS Thirteen subjects with Type 2 diabetes mellitus were studied in a double-blind crossover design with 4-week placebo run-in and washout and 12-week treatment periods , r and omised to micronised fenofibrate 267 mg or atorvastatin 10 mg daily followed by the alternate drug in the second period . Insulin resistance was measured using the isoglycaemic hyperinsulinaemic clamp method with isotope dilution . RESULTS Weight , physical activity and other medications did not change . Total cholesterol ( mean + /- st and ard error ) was 4.60+/-0.21 versus 3.9+/-0.22 mmol/L after fenofibrate and atorvastatin respectively , p<0.05 . LDL was 2.70+/-0.19 versus 1.95+/-0.23 mmol/L , p<0.05 and triglyceride 1.64+/-0.23 versus 1.84+/-0.26 mmol/L , p<0.05 . Insulin-stimulated whole-body glucose disposal ( 35.4+/-3.1 versus 33.2+/-3.0 μmol/kg/min ) and nadir endogenous glucose production ( 6.2+/-1.4 versus 7.0+/-1.1 μmol/kg/min ) revealed no significant differences in effects of the treatments . CONCLUSIONS In human subjects with Type 2 diabetes mellitus there were characteristic differences in lipid profile changes but no difference in insulin sensitivity after treatment with micronised fenofibrate compared to atorvastatin . This study finds no evidence of increased insulin sensitivity using this selective PPAR-alpha agonist over a commonly used statin at these doses
target: 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: 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 .