title: Sulodexide in the treatment of intermittent claudication. Results of a randomized, double-blind, multicentre, placebo-controlled study. Olive oil- and fish oil-enriched diets modify plasma lipids and susceptibility of LDL to oxidative modification in free-living male patients with peripheral vascular disease: the Spanish Nutrition Study. Double-blind multicenter trial on a new medium molecular weight glycosaminoglycan. Current therapeutic effects and perspectives for clinical use. Effect of extra-virgin olive oil and fish-oil supplementation on plasma lipids and susceptibility of low-density lipoprotein to oxidative alteration in free-living spanish male patients with peripheral vascular disease. Lowering of HDL2b by probucol partly explains the failure of the drug to affect femoral atherosclerosis in subjects with hypercholesterolemia. A Probucol Quantitative Regression Swedish Trial (PQRST) Report. The Cholesterol Lowering Atherosclerosis Study (CLAS): design, methods, and baseline results. Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease. Effects of 3-Glucosaminoglycan Sulfate on Hemorheologic Parameters in Hyperlipidemic Peripheral Vascular Disease (PVD) Patients Effects of colestipol-niacin therapy on human femoral atherosclerosis. Increased plasma levels of tissue factor pathway inhibitor (TFPI) after n-3 polyunsaturated fatty acids supplementation in patients with chronic atherosclerotic disease. Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment. Bezafibrate in men with lower extremity arterial disease: randomised controlled trial Design and intermediate results of the Lower Extremity Arterial Disease Event Reduction (LEADER)* trial of bezafibrate in men with lower extremity arterial disease [ISRCTN41194621] Rationale and design of the Arterial Disease Multiple Intervention Trial (ADMIT) pilot study. Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids. The Oxford Cholesterol Study Group. Genetic determinants of the response to bezafibrate treatment in the lower extremity arterial disease event reduction (LEADER) trial. Probucol Quantitative Regression Swedish Trial: new angiographic technique to measure atheroma volume of the femoral artery. Comparison of computer- and human-derived coronary angiographic end-point measures for controlled therapy trials. Cholesterol Reduction With Atorvastatin Improves Walking Distance in Patients With Peripheral Arterial Disease Effects of Policosanol and Ticlopidine in Patients with Intermittent Claudication: A Double-Blinded Pilot Comparative Study Treatment of Intermittent Claudication with Antiplatelet Agents A comparison of low versus standard dose pravastatin therapy for the prevention of cardiovascular events in the elderly: the pravastatin anti-atherosclerosis trial in the elderly (PATE). Compliance to multiple interventions in a high risk population. Efficacy and safety of cerivastatin and pravastatin in the treatment of primary hypercholesterolemia. The effect of probucol on low density lipoprotein oxidation and femoral atherosclerosis. Plasma lipid levels and platelet and neutrophil function in patients with vascular disease following fish oil and olive oil supplementation. Lowering of Plasma Viscosity by the Oral Administration of the Glycosaminoglycan Sulodexide in Patients with Peripheral Vascular Disease The MRC/BHF Heart Protection Study: preliminary results. Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. Effects of Policosanol and Lovastatin in Patients with Intermittent Claudication: A Double-Blind Comparative Pilot Study Randomised controlled trial of the treatment of hyperlipidaemia on progression of atherosclerosis. Effect of sulodexide on blood viscosity in patients with peripheral vascular disease. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial. Fish oil supplementation in patients with stable claudication. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. Effects of Probucol versus Aspirin and versus Brachytherapy on Restenosis after Femoropopliteal Angioplasty: The PAB Randomized Multicenter Trial Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease. The Effectiveness of Glycosaminoglycans in Peripheral Vascular Disease Therapy: A Clinical and Experimental Trial A Double-Blind, Placebo-Controlled Study of the Effects of Policosanol in Patients with Intermittent Claudication Decrease in P-selectin levels in patients with hypercholesterolaemia and peripheral arterial occlusive disease after lipid-lowering treatment The role of lipids and antioxidative factors for development of atherosclerosis. The Probucol Quantitative Regression Swedish Trial (PQRST). Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Sunflower oil does not protect against LDL oxidation as virgin olive oil does in patients with peripheral vascular disease. The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST). A Long-Term Study of Policosanol in the Treatment of Intermittent Claudication The treatment of intermittent claudication with betapyridyl carbinol over two years. Effective and safe modification of multiple atherosclerotic risk factors in patients with peripheral arterial disease. A controlled trial of plasma lipid reduction in peripheral atherosclerosis—an interim report Reducing blood cholesterol levels in patients with peripheral vascular disease: dietitian or diet fact sheet? Cost-effectiveness of simvastatin in people at different levels of vascular disease risk: economic analysis of a randomised trial in 20,536 individuals. Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study. Effects of dietary manipulation on vascular status of patients with peripheral vascular disease. The peripheral circulation and treatment of hyperlipoproteinemias. Niacin treatment increases plasma homocyst(e)ine levels. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. [Statins in the treatment of patients with arterial occlusive disease of the lower extremities]. Effect of niacin, warfarin, and antioxidant therapy on coagulation parameters in patients with peripheral arterial disease in the Arterial Disease Multiple Intervention Trial (ADMIT). Xanthinol nicotinate in peripheral vascular disease. TREATMENT OF HYPERLIPIDAEMIA RETARDS PROGRESSION OF SYMPTOMATIC FEMORAL ATHEROSCLEROSIS: A Randomised Controlled Trial
abstract: AIMS Patients with peripheral arterial obstructive disease require treatment to prevent major cardiovascular events and to relieve intermittent claudication . The walking performance of peripheral arterial obstructive disease patients was used to evaluate the usefulness of sulodexide , a glycosaminoglycan containing fast moving heparin and dermatan sulphate . METHODS AND RESULTS A r and omized , multicentre , double-blind , placebo-controlled study was performed in 286 patients with Leriche-Fontaine stage II peripheral arterial obstructive disease . Patients received placebo ( n=143 ) or sulodexide ( n=143 ) for 27 weeks . The primary end-point was the doubling of the pain-free walking distance at the end of treatment , and this was achieved by 23.8 % of patients treated with sulodexide and 9.1 % of those on placebo ( P=0.001 ) . The pain-free walking distance increased on average ( + /-SE ) by 83.2+/-8.6 m ( + 64.7 % from baseline ) with sulodexide and 36.7+/-6.2 m ( + 29.9 % from baseline ) with placebo ( P=0.001 ) . The maximum walking distance increased by 142.3+/-15.8 m ( + 76.0 % from baseline ) and 54.5+/-8.4 m ( + 27.9 % from baseline ) ( P<0.001 ) , respectively . Results for patients with type II diabetes were similar to those for non-diabetic patients .  Plasma fibrinogen decreased with sulodexide , but increased with placebo . CONCLUSION Sulodexide improved the walking ability of peripheral arterial obstructive disease patients to a significantly greater extent than placebo , with a concurrent significant decrease in fibrinogen . The treatment was well tolerated The present study describes a clinical trial in which Spanish patients suffering from peripheral vascular disease ( Fontaine stage II ) were given specific lipid supplements . Design ed as a longitudinal intervention study , patients were provided with olive oil for 3 months , followed by a 3 month wash-out period , then supplemented with a combination of fish oil and olive oil for the final 3 months . Changes in plasma and lipoprotein fatty acid composition and susceptibility of LDL to in vitro oxidation were examined . Furthermore , lipid-supplement-induced changes in LDL properties were measured as relative electrophoretic mobility and macrophage uptake . In addition , thirteen patients not provided with olive oil and fish oil were included as a control group and twenty healthy age-matched individuals were used as a reference group . A complete clinical study and a nutritional survey concerning food habits and lifestyle were performed every 3 months . Yao indices and claudicometry did not change significantly with dietary intervention although changes in plasma lipid composition suggested an improvement in the condition of the patients . The intake of the fish-oil supplement result ed in significantly increased plasma levels of eicosapentaenoic acid ( 20:5n-3 ) and docosahexaenoic acid ( 22:6n-3 ) in comparison with baseline concentrations , olive-oil and control groups . Fish-oil consumption significantly decreased plasma triacylglycerol levels compared with the olive-oil period , control and reference groups . The susceptibility of LDL to Cu-mediated oxidation was lower in the patients consuming olive oil and the fish-oil supplement than in the control group , and the uptake of LDL by macrophages was significantly lower in the group supplemented with fish oil . In conclusion , consumption of olive oil together with a dietary supplement of fish oil may be useful in the nutritional management of patients suffering from peripheral vascular disease in terms of increasing plasma n-3 long-chain polyunsaturated fatty acids and decreasing susceptibility of LDL to oxidation The ability of glycosaminoglycans to bind to a wide number of biologically active macromolecules has already been investigated . Recent clinical trials on the possible therapeutic benefits of glycosaminoglycans must be placed in perspective , even if they appear to be particularly encouraging , especially as regards the glycosaminoglycan effects on certain coagulation factors . A multicenter , medium-term , double-blind , crossover trial was performed by several Italian Lipid Clinics to determine whether administration of a medium molecular weight glycosaminoglycan ( Sulodexide ) has a significant clinical effect . Patients affected by peripheral vascular disease and /or hyperlipidemia ( type IIa , IIb and IV ) were su bmi tted to a 4-week wash-out period , followed by parenteral Sulodexide ( S ) or placebo ( P ) administration for 2 weeks , another 2 week wash-out period , parenteral crossover drug or P administration for 2 weeks and , finally , oral S administration for 6 months . Sulodexide lowered plasma viscosity and plasma fibrinogen in all patients . There was also a drop in triglycerides together with a rise in apo A-I and HDL-C in type IV hyperlipoproteinemics , whereas there was no significant effect on total or LDL-plasma cholesterol in type IIa and IIb patients . Moreover , there was a percent increase in peak flow and rest flow in the lower limbs of peripheral vascular disease patients . No side effects or intolerance phenomena were detected . The results indicate that Sulodexide administration may be useful in long-term treatment of patients with peripheral vascular disease and a concomitant increase in plasma triglycerides and /or fibrinogen and /or viscosity The aim of this study was to analyse the in vivo effect of a diet rich in extra-virgin olive oil and a fish-oil supplement on plasma and lipoprotein fatty-acid composition and on LDL susceptibility to oxidative modification in free-living Spanish male patients with peripheral vascular disease . A total of 12 patients were included in the experimental group which received extra virgin olive oil and a fish oil supplement ( group OF ) . On the other h and , 13 patients which had refined olive oil as the main visible fat were considered as Control group . Plasma triglycerides decreased significantly after three months of dietary intervention . The LDL and plasma fatty-acid pattern in the group OF was characterized by a significant increase in n-3 polyunsaturated fatty acids , mainly 20:5 n-3 and 22:6 n-3 . The slopes of LDL oxidative susceptibility were similar between baseline and endpoint values in both groups . However , the uptake of oxidized LDL by macrophages was significantly reduced in OF patients in comparison with the Control group . In conclusion , the daily intake of about 40 g/d of extra-virgin olive oil in combination with a daily supplement of 16 g of fish oil for 3 months in patients with peripheral vascular disease leads to a plasma-lipid profile less atherogenic than in patients having refined olive oil as the main visible food fat . The simultaneous consumption of alpha-tocopherol and natural antioxidants provided by extra-virgin olive oil seems to have a protective effect on the LDL susceptibility to oxidative modifications in spite of a higher proportion of n-3 polyunsaturated fatty acids The aim of the Probucol  Quantitative Regression Swedish Trial ( PQRST ) ( n = 303 ) was to investigate whether probucol ( 0.5 g BID ) added to diet and cholestyramine ( 8 g BID ) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic ( > 6.86 mmol/L ) subjects .  Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery . In this report we studied in a representative subgroup ( n = 72 ) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective . We analyzed the effects of treatment on HDL particle size subclasses . Probucol lowered the relative level of HDL2b , comprising the largest HDL particles , by 53 % and the protein concentration of HDL2b by 67 % . The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety . The change in lumen volume correlated significantly with change in HDL , ie , HDL cholesterol ( r = .34 , P < .01 ) , HDL2 cholesterol ( r = .37 , P < .01 ) , HDL2b protein ( r = .44 , P < .001 ) , and the relative HDL2b value ( r = .51 , P < .001 ) . The corresponding values for relative HDL2b , distribution calculated on the active ( n = 35 ) and placebo ( n = 37 ) groups separately were also significant ( r = .39 and .32 , respectively ; both P < .05 ) . The correlation between drug-induced change in the relative HDL2b concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction . ( ABSTRACT TRUNCATED AT 250 WORDS The Cholesterol Lowering Atherosclerosis Study ( CLAS ) is a prospect i ve , placebo-controlled , angiographic trial design ed to test the hypothesis that aggressive lowering of LDL cholesterol with concomitant increase in HDL cholesterol will reverse or retard the atherosclerotic process . Specifically , CLAS was design ed to determine whether combined therapy with colestipol plus niacin will produce clinical ly significant change in coronary , carotid , and femoral artery atherosclerosis and coronary bypass graft lesions . To this purpose , 188 subjects were r and omized to diet plus drug or diet plus placebo .  We report on method ological aspects of planning and evaluating this study , including the choice of the study population , procedures for recruitment , the experimental design including sample size considerations , methods for evaluating outcome , and methods for evaluating compliance to treatment . Comparison of baseline data indicated no significant differences between groups at the time of r and omization . Subjects were predominantly male , Caucasian , 54 years of age , 20 % above ideal weight , with normal blood pressure . The average age at bypass was 50 years . The average lipids were cholesterol ( 243 mg/dL ) , HDL ( 45 mg/dL ) , and LDL ( 168 mg/dL ) . Finally , the distribution of baseline coronary stenosis was equivalent between the two groups ( average number of lesions per subject = 10.6 ) BACKGROUND AND AIMS epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis . The aim of this study was to perform a r and omized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis . Main outcome measures were : cholesterol and lipoprotein concentrations ; haemostatic and rheological variables ; the ankle brachial pressure index ; walking distance ; and cardiovascular events and death . METHODS 120 men and women with stable intermittent claudication were r and omized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids , or placebo . RESULTS 39 ( 65.0 cent ) of those taking fatty acids and 36 ( 60.0 cent ) of those taking placebo completed the trial . Lipid concentrations did not differ significantly during the trial . In those taking fatty acids , haematocrit was significantly higher than in the placebo group after 6 months ( 46.1 cent compared with 44.6 cent , P < /= 0.01 ) , and systolic blood pressure was significantly lower after 2 years ( 150|mmHg compared with 161.8|mmHg , < /= 0.05 ) . There was no difference in walking distance , but there was a small reduction in non-fatal coronary events in the fatty acid group ( 10 cent compared with 15 cent , P > 0.05 ) . CONCLUSIONS a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure , but no other significant benefits on risk factors . The trend towards fewer coronary events in those taking fatty acids warrants further investigation The effects of 3-glucosaminoglycan sulfate on lipids and the hemorheologic parameters were observed in a preliminary double-blind crossover study in 30 hyperlipidemic peripheral vascular disease ( PVD ) patients . Parenteral adminis tration of the test drug was associated with a reduction in serum lipids , espe cially in triglyceride levels , and a lowering of fibrinogen , plasma viscosity , and whole blood viscosity levels . These effects justify the drug 's use in the treatment of PVD , especially when associated with hypertriglyceridemia and hemorheo logic disturbances The 2-year therapy effect on femoral atherosclerosis was evaluated in the Cholesterol Lowering Atherosclerosis Study ( CLAS ) , a r and omized , placebo-plus-diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men with previous coronary bypass surgery . Different diet compositions were prescribed to enhance the differential in blood cholesterol responses between the two groups . The annual rate of change in computer-estimated atherosclerosis ( CEA ) , a measure of lumen abnormality , was evaluated between treatment groups . A significant per-segment therapy effect was found in segments with moderately severe atherosclerosis ( p less than 0.04 ) and in proximal segments ( p less than 0.02 ) . When segmental CEA measures were combined into a per-patient score using an adaptation of the National Heart , Lung , and Blood Institute scoring procedure , a significant therapy effect was observed ( p less than 0.02 ) . Total variance of the annual change rate in CEA was as predicted from pilot studies , but measurement variation was larger . The therapy effect observed in femoral arteries , although significant , was less marked than the strong and consistent benefit previously reported for both native coronary arteries and aortocoronary bypass grafts This double-blind , r and omised , controlled study examined the effect of a daily dosage of 3 g n-3 polyunsaturated fatty acids ( n-3 PUFA ) on plasma lipids and some haemostatic factors in 40 patients with chronic atherosclerotic diseases .  Serum lipids , factor VII , tissue factor pathway inhibitor ( TFPI ) and prothrombin activation fragment 1 + 2 ( F1 + 2 ) were measured at baseline and after 2 , 8 , and 16-week supplementation of either n-3 PUFA or corn oil . Administration of n-3 PUFA promptly lowered serum triglycerides and increased LDL-cholesterol ( -32 % and + 33 % , respectively , after 2 weeks of treatment ) while a significant increase ( + 31 % ) in HDL-cholesterol was documented at the end of the observation period . Treatment with n-3 PUFA induced a progressive significant increase of TFPI plasma levels ( + 21 % after 16 weeks ; p = 0.029 ) . TFPI activity was significantly correlated with LDL-cholesterol , and multiple stepwise regression analysis showed that LDL-cholesterol was the most important predictor of TFPI activity . Plasma levels of the inhibitor showed also a very high parallelism in their trend over time ( ANOVA model for homogeneity of slopes ) with both HDL-cholesterol ( p = 0.82 ) and LDL-cholesterol ( p = 0.67 ) . Patients treated with n-PUFA also showed a significant reduction of F1 + 2 plasma levels ( p = 0.016 ) while no significant changes were detected in plasma factor VII clotting activity . Lipid and haemostatic parameters were not modified at any study time in patients receiving corn oil as placebo . The results of this study confirm the effects of n-3 PUFA administration on plasma lipids and show that in patients with chronic atherosclerotic disease a 16-week supplementation with these compounds induces a small but statistically significant increase of TFPI plasma levels with a parallel down-regulation of the extrinsic pathway of blood coagulation which may be relevant to the antithrombotic activity of fish diet and fish oil derivatives Simvastatin significantly increased treadmill exercise time until onset of intermittent claudication from baseline by 54 seconds ( a 24 % increase , p < 0.0001 ) at 6 months after treatment and by 95 seconds ( a 42 % increase , p < 0.0001 ) at 1 year after treatment . At 6 months and 1 year after treatment with placebo , treadmill exercise time until onset of intermittent claudication was not significantly different from baseline exercise time Objective : To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease . Design : Double blind placebo controlled r and omised trial . Setting : 85 general practice s and nine hospital vascular clinics . Participants : 1568 men , mean age 68.2 years ( range 35 to 92 ) at recruitment . Interventions : Bezafibrate 400 mg daily ( 783 men ) or placebo ( 785 men ) . Main outcome measures : Combination of coronary heart disease and of stroke . All coronary events , fatal and non-fatal coronary events separately , and strokes alone ( secondary end points ) . Results : Bezafibrate did not reduce the incidence of coronary heart disease and stroke . There were 150 and 160 events in the active and placebo groups respectively ( relative risk 0.96 , 95 % confidence interval 0.76 to 1.21 ) . There were 90 and 111 major coronary events in the active and placebo groups respectively ( 0.81 , 0.60 to 1.08 ) , of which 64 and 65 were fatal ( 0.95 , 0.66 to 1.37 ) and 26 and 46 non-fatal ( 0.60 , 0.36 to 0.99 ) . Beneficial effects on non-fatal events were greatest in men aged < 65 years at entry , in whom benefit was also seen for all coronary events ( 0.38 , 0.20 to 0.72 ) . There were no significant effects in older men . There were 60 strokes in those on active treatment and 49 in those on placebo ( 1.34 , 0.80 to 2.01 ) . There were 204 and 195 deaths from all causes in the two groups respectively ( 1.03 , 0.83 to 1.26 ) . Bezafibrate reduced the severity of intermittent claudication for up to three years . Conclusions : Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events , particularly in those aged < 65 years at entry , in whom all coronary events may also be reduced Background Raised levels of both triglycerides and fibrinogen , each of which are reduced by bezafibrate , may contribute to lower extremity arterial disease ( LEAD ) . This condition is characterized by a particularly high incidence of coronary heart disease ( CHD ) and stroke , but is little studied thus far in r and omised controlled trials . Method Patients were recruited through 85 practice s in the British Medical Research Council General Practice Research Framework and through nine hospital vascular clinics . The treatment regimen , which is double-blind and placebo-controlled , is bezafibrate 400 mg/day . The 1568 patients recruited represent 86 % of those eligible at screening . Results None of the anticipated side effects ( mainly gastrointestinal ) differed between the two groups . Nearly 80 % of the total person-years accrued at 3 years were spent on trial treatment . Bezafibrate significantly reduced total cholesterol by approximately 8.0 % and low-density lipoprotein (LDL)-cholesterol by approximately 9.0 % , and increased high-density lipoprotein (HDL)-cholesterol by approximately 11.0 % initially , falling to about 6.0 % at 3 years . Triglycerides were significantly reduced by about 23.0 % and fibrinogen by about 14.0 % . Plasma creatinine rose by approximately 11 % in those on active treatment . All of these effects were highly significant ( P < 0.0001 ) . Bezafibrate had no effect on the level of C-reactive protein ( CRP ) . Conclusion The trial recruited an unusually high proportion of eligible patients , ensuring the general applicability of its results . The fibrinogen-lowering and lipid-modifying effects of bezafibrate were confirmed . Although bezafibrate lowers fibrinogen , it has no effect on CRP ; this suggests that the reduction in fibrinogen is due to an effect on its metabolism rather than suppression of an inflammatory response The primary objectives of the pilot study were to : ( 1 ) evaluate the feasibility of recruiting patients with peripheral arterial disease ( PAD ) ; ( 2 ) measure the efficacy and safety of high-density lipoprotein (HDL)-raising treatment , low-density lipoprotein (LDL)-lowering therapy , antioxidant therapy , antithrombotic therapy , and their combinations ; and ( 3 ) assess adherence to a complex multiple drug regimen . Secondary objectives included measurement of the effect of the interventions on prespecified biochemical markers , maintenance of therapy masking ( in particular with niacin ) , and measurement of the intervention 's impact on functional status and on quality of life . To date , no secondary prevention trial has been conducted specifically among patients with PAD . Intermittent claudication affects about 0.5 % to 1.0 % of persons aged > 35 years . There is a striking increase in incidence of PAD with age , particularly among those aged > 50 years in both sexes , although men are twice as likely as women to develop PAD . The Arterial Disease Multiple Intervention Trial was a double-blind r and omized pilot trial of 468 participants with documented PAD . A 2 x 2 x 2 factorial design was used to evaluate the effect of 3 interventions . The pilot incorporated several major novel design features : first , the use of a simple noninvasive method ( measurement of ankle brachial index ) to identify a population with either symptomatic or asymptomatic PAD ; and second , a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as needed in the intervention and control group . Two other arms , the antioxidant arm ( consisting of beta-carotene and vitamins E and C ) and the antithrombotic arm ( using warfarin ) were also added . Adherence to therapy was measured by pill count , and success in treatment was measured by the proportion of values in target range for HDL , LDL , and the international normalized ratio The Oxford Cholesterol Study is a r and omized placebo-controlled trial design ed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large , long-term trial of the effects of cholesterol-lowering drug therapy on mortality . At present there is only limited evidence from r and omized comparisons of the effects of HMG-CoA reductase inhibitors , such as simvastatin , on thrombogenic , as distinct from atherogenic , pathways in coronary heart disease . The present sub- study was carried out to assess the effects of simvastatin on a range of haemostatic variables , as well as on free fatty acids and on lipoprotein fractions not studied in detail previously . At an average of about 2 years after starting study treatment , non-fasting blood sample s were obtained from a sequential sample of 162 participants who had been r and omly allocated to receive 40 mg ( 54 patients ) or 20 mg ( 57 patients ) daily simvastatin or matching placebo treatment ( 51 patients ) . Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included . The principal comparisons were to be of those allocated simvastatin ( i.e. 20 and 40 mg doses combined ) vs those allocated placebo . Among patients allocated simvastatin , marginally significant lower factor VII antigen levels ( 12.10 % + /- 6.08 of st and ard ; 2P < 0.05 ) and non-significantly lower factor VII coagulant activity ( 8.24 % + /- 4.99 of st and ard ) and fibrinogen concentrations ( 0.10 + /- 0.08 g. l-1 ) were observed . In contrast , plasminogen activator inhibitor activity was significantly higher ( 2.62 + /- 1.03 IU ; 2P < 0.01 ) among patients allocated simvastatin . No significant differences were seen in the other haemostatic factors studied ( e.g. prothrombin fragment 1.2 , factor XII and C1 inhibitor ) . Total free fatty acid concentration was marginally significantly reduced ( 2P = 0.02 ) with simvastatin , but none of the reductions in individual free fatty acids was significant . Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo . Compared with placebo , simvastatin produced significant decreases not only in LDL cholesterol ( 1.74 + /- 0.15 mmol.1(-1 ) : 2P < 0.0001 ) but also in VLDL cholesterol ( 0.28 + /- 0.08 mmol.1(-1 ) ; 2P < 0.001 ) and IDL cholesterol ( 0.17 + /- 0.03 mmol.1(-1 ) ; 2P < 0.0001 ) . There were also lower triglyceride levels associated with LDL ( 0.07 + /- 0.01 mmol.1(-1 ) ; 2P < 0.0001 ) , IDL ( 0.03 + /- 0.01 mmol.1(-1 ) ; 2P < 0.01 ) and VLDL ( 0.27 + /- 0.14 ; 2P = 0.05 ) . The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects . Given the associations of haemostatic factors with coronary heart disease incidence , larger r and omized comparisons of the HMG-CoA reductase inhibitors ( and of the newer fibrates which may produce greater effects ) are needed to provide more reliable estimates of the extent to which they influence these variables Genetic determinants of baseline levels and the fall in plasma triglyceride and fibrinogen levels in response to bezafibrate treatment were examined in 853 men taking part in the lower extremity arterial disease event reduction ( LEADER ) trial . Three polymorphisms in the peroxisome proliferator activated receptor alpha ( PPARalpha ) gene were investigated ( L162V , G > A in intron 2 and G > C in intron 7 ) , two in the apolipoprotein CIII ( APOC3 ) gene ( -482C > T and -455T > C ) and one in the beta-fibrinogen ( FIBB ) gene ( -455G > A ) . The presence of diabetes ( n=158 ) was associated with 15 % higher triglyceride levels at baseline compared to non-diabetics ( n=654 ) ( P<0.05 ) . Among the diabetic group , carriers of the PPARalpha intron 7 C allele had 20 % lower triglyceride levels compared to homozygotes for the common G allele ( P<0.05 ) , with a similar ( non-significant ) trend for the L162V polymorphism , which is in linkage disequilibrium with the intron 7 polymorphism . For the APOC3 gene , carriers of the -482 T allele had 13 % lower baseline triglyceride levels compared to -482C homozygotes ( P<0.02 ) , but no effect was observed with the -455T > C substitution . In the non-diabetic patients , the PPARalpha V162 allele was significantly associated with 9 % higher baseline triglyceride levels ( P<0.03 ) and a similar , but non-significant trend was seen for the intron 7 polymorphism . Overall , triglyceride levels fell by 26 % with 3 months of bezafibrate treatment , and current smokers showed a poorer response compared to ex/non-smokers ( 23 % fall compared to 28 % P=0.03 ) , but none of the genotypes examined had a significant influence on the magnitude of response . Carriers of the -455A polymorphism of the FIBB gene had , as expected , marginally higher baseline fibrinogen levels , 3.43 versus 3.36 g/l ( P=0.055 ) , but this polymorphism did not affect response to treatment . Overall , fibrinogen levels fell by 12 % , with patients with the highest baseline fibrinogen levels showing the greatest decrease in response to bezafibrate . For both the intron 2 and the L162V polymorphisms of the PPARalpha gene there was a significant interaction ( both P<0.01 ) between genotype and baseline levels of fibrinogen on the response of fibrinogen levels to bezafibrate , such that individuals carrying the rare alleles in the lowest tertile showed essentially no overall decrease compared to a 0.18 g/l fall in homozygotes for the common allele . Thus while these genotypes are a minor determinant of baseline triglyceride and fibrinogen levels , there is little evidence from this study that the magnitude of response to bezafibrate treatment in men with peripheral vascular disease is determined by variation at these loci The Probucol Quantitative Regression Swedish Trial is study ing the development of atherosclerosis in hyperlipidemic patients through the use of digitized femoral arteriographic examinations . In a 20-cm segment of the femoral artery , cross-sectional areas are calculated using an algorithm that was introduced by Hilal and Crawford . Changes in atheroma volume are measured in repeat arteriographic examinations . This report describes the radiologic technique , the scanning procedure and the image analysis The Cholesterol Lowering Atherosclerosis Study , a r and omized angiographic clinical trial , demonstrated the beneficial effect of niacin/colestipol plus diet therapy on coronary atherosclerosis . Outcome was determined by panel-based estimates ( viewed in both still and cine modes ) of percent stenosis severity and change in native artery and bypass graft lesions . Computer-based quantitative coronary angiography ( QCA ) was also used to measure lesion and bypass graft stenosis severity and change in individual frames closely matched in orientation , opacification , and cardiac phase . Both methods jointly evaluated 350 nonoccluded lesions . The correlation between QCA and panel estimates of lesion size was 0.70 ( p less than 0.0001 ) and for change in lesion size was 0.28 ( p = 0.002 ) . Agreement between the two methods in classifying lesion changes ( i.e. , regression , unchanged , or progression ) occurred for 60 % ( 210 of 350 ) of the lesions kappa + /- SEM = 0.20 + /- 0.05 , p less than 0.001 ) . The panel identified 442 nonoccluded lesions for which QCA stenosis measurements could not be obtained . Lesions not measurable by QCA included those with stenosis greater than 85 % that could not be reliably edge tracked , segments with diffuse or ecstatic disease that had no reliable reference diameter , and segments for which matched frames could not be located . Seventy-nine lesions , the majority between 21 % and 40 % stenosis , were identified and measured by QCA but were not identified by the panel . This comparison study demonstrates the need to consider available angiographic measurement methods in relation to the goals of their use Background —Cholesterol modification reduces cardiovascular events in patients with atherosclerosis , including those with peripheral arterial disease . The purpose of this study was to determine whether cholesterol lowering with atorvastatin improves walking performance in patients with intermittent claudication . Methods and Results —This r and omized , double-blind , parallel- design study included 354 persons with claudication attributable to peripheral arterial disease . Patients were treated with placebo , atorvastatin ( 10 mg per day ) , or atorvastatin ( 80 mg per day ) for 12 months . The outcome measures included change in treadmill exercise time and patient-reported measures of physical activity and quality of life based on question naires . Maximal walking time after 12 months of treatment with atorvastatin did not change significantly . However , there was improvement in pain-free walking time after 12 months of treatment for the 80-mg ( P = 0.025 ) group compared with placebo . A physical activity question naire demonstrated improvement in ambulatory ability for the 10- and 80-mg groups ( P = 0.011 ) , whereas 2 quality of life instruments , the Walking Impairment Question naire and Short Form 36 Question naire , did not show significant change . Conclusions —Atorvastatin improves pain-free walking distance and community-based physical activity in patients with intermittent claudication . When treated with atorvastatin , patients with peripheral arterial disease may experience improvement in symptoms to complement the anticipated reduction in cardiovascular events reported in other studies of statins Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects . The present study was undertaken to compare the effects of policosanol and ticlopidine in patients with moderately severe intermittent claudication ( IC ) . The study had a 4-week baseline step , followed by a 20-week double-blinded , r and omized treatment period . Twenty-eight eligible patients were r and omized to  policosanol 10 mg  or ticlopidine  250 mg tablets twice daily ( bid ) . Walking distances in a treadmill ( constant speed 3.2 km/hr , slope 10 ° , temperature 25 ° C ) were assessed before and after 20 weeks of treatment . Both groups were similar at baseline . Compared with baseline , policosanol significantly increased ( p<0.01 ) mean values of initial ( ICD ) and absolute ( ACD ) claudication distances from 162.1 to 273.2 m and from 255.8 to 401.0 m , respectively . Ticlopidine also raised significantly ( p<0.01 ) ICD ( 166.2 to 266.3 m ) and ACD ( 252.9 to 386.4 m ) . Comparisons between groups did not show significant differences . Policosanol , but not ticlopidine , significantly ( p<0.05 ) , but modestly , increased the ankle/arm pressure ratio . After 10 weeks , policosanol significantly ( p<0.001 ) lowered low-density lipoprotein-cholesterol ( LDL-C ) , total cholesterol ( TC ) ( p<0.01 ) , and TC/HDL-C and raised ( p<0.05 ) high-density lipoprotein-cholesterol ( HDL-C ) . At study completion , policosanol  lowered ( p<0.001 ) LDL-C ( 30.2 % ) , TC ( 16.9 % ) , and TC/HDL-C ( 33.9 % ) , increased ( p<0.01 ) HDL-C ( + 31.7 % ) , and left triglycerides  unchanged . Ticlopidine did not affect the lipid profile variable . Policosanol induced modest , but significant , reductions ( p<0.01 ) of fibrinogen levels compared with baseline and ticlopidine . Treatments were well tolerated and did not impair safety indicators .  Three ticlopidine patients ( 21.4 % ) withdrew from the trial , only 1 owing to a serious adverse experience ( AE ) ( unstable angina ) . Three other ticlopidine patients experienced mild AE ( headache , diarrhea , and acidity ) . It is concluded that policosanol ( 10 mg bid ) can be as effective as ticlopidine ( 250 mg bid ) for improving walking distances of claudicant patients , and it could be advantageous for the global risk of these individuals owing to its cholesterol-lowering effects . This study is , however , just a pilot comparison , so that further studies in larger sample sizes are needed for definitive conclusions of the comparative effects of both drugs on patients with IC In a double-blind study , 296 patients with intermittent claudication ( Fontaine stage II ) were treated with 250 mg ticlopidine twice daily , 500 mg aspirin every third day plus 75 mg dipyridamole three times daily , or 300 mg xanthinol nicotinate three times daily for 6 months . Ticlopidine and aspirin/dipyridamole , but not xanthinol nicotinate , improved platelet aggregation , reduced β-thromboglobulin , platelet factor IV and fibrinopeptide A concentrations , and increased antithrombin III concentrations and red blood cell filterability . No changes in lipid profiles , platelet count or fibrinogen were recorded following any treatment . The doppler systolic blood pressure ratio was improved in patients treated with ticlopidine or aspirin/dipyridamole , but not with xanthinol nicotinate . It is concluded that antiplatelet treatment is useful for the treatment of limb arteriopathy Treatment with low drug doses is generally recommended in the elderly . However , the efficacy of low dose 3-hydroxy-3-methylglutaryl coenzyme A ( HMG CoA ) reductase inhibitor treatment in elderly hypercholesterolemic patients has never been examined . Therefore , we compared the effect of low-dose with st and ard dose pravastatin , an HMG CoA reductase inhibitor , on the incidence of cardiovascular events ( CVEs ) in elderly patients with hypercholesterolemia in a r and omized prospect i ve trial . Subjects aged > or = 60 years ( 73 + /- 6 years ) with serum total cholesterol ( TC ) levels of 220 - 280 mg/dL were r and omized to the low-dose ( groupL , 5 mg/day ; n=334 ) or st and ard dose ( groupS , 10 - 20mg/day ; n= 331 ) . Baseline TC levels were similar in the 2 groups ( 253 + /-15 mg/dL ) . Patients were followed for 3 - 5 years ( mean 3.9 years ) . TC levels decreased from baseline by 11 - 13 % in group L and by 15 - 17 % in groupS. TC levels at 1 year in S and L group were 209 + /- 2 mg/ dL ( 16 + /- 1 % decrease ) and 221+/- 2 mg/dL ( 12 + /- 1 % decrease ) , respectively . Forty two and 29 CVEs occurred in group L and S , respectively . The incidence of CVEs was significantly lower in group S than in group L ( P = 0.046 , generalized Wilcoxon test ; P = 0.096 , log-rank test ) . The risk ratio for group S compared with group L was 0.674 ( 95 % confidence interval : 0.423 - 1.074 ) . Subgroup analyses suggested that the difference in the incidence of CVEs between the 2 groups was more clear in subjects without diabetes mellitus , with TC levels of < 253 mg/dL , and with TG levels of > or = 133 mg/dL. The incidence of CVEs in group S was significantly lower than that in group L in subjects without both diabetes mellitus and previous cardiovascular disease ( P = 0.026 , generalized Wilcoxon test ; P = 0.032 , log rank test ) . These findings suggest that st and ard-dose pravastatin ( 10 - 20 mg/day ) is more effective in reducing the incidence of CVEs in the elderly than low dose pravastatin ( 5 mg/ day ) , especially in nondiabetic elderly patients with mild hypercholesterolemia or previous cardiovascular disease PURPOSE Assess compliance with study medications and examine reasons for noncompliance .  Individuals with peripheral arterial disease present the clinician with a unique combination of symptoms and therapeutic needs ; the treatment of this population has not been adequately studied . METHODS The Arterial Disease Multiple Intervention Trial was a r and omized double-blind placebo-controlled trial that r and omized 468 participants to a combination of antioxidants , niacin and warfarin or matching placebos . Men and women ( mean age 65 yrs ) with peripheral arterial disease and low-density lipoprotein ( LDL ) < 190 mg/dl were enrolled and followed for one year . Compliance to the study medications was measured by pill count for each medication . An overall measure of compliance was determined by combining pill counts from all study visits . RESULTS Mean overall pill counts ranged from 88 to 94 % in the eight treatment groups . No statistically significant differences were found in mean pill counts over time or between active and placebo groups . History of coronary artery disease and number of follow-up visits were associated with higher overall pill counts while low compliance during screening was associated with lower counts during follow-up . Participants with an overall mean pill count < 80 % had more adverse events compared to those with a higher count . Side effects were reported as the reason for missing pills significantly more often in the active versus placebo niacin group . CONCLUSIONS Individuals with peripheral arterial disease were able to comply with the complex drug regimen . The ability of this drug combination to reduce cardiovascular events and improve quality of life warrants study In this r and omized , double-blind , parallel group study , the efficacy and safety of cerivastatin ( 0.3 mg ) and pravastatin ( 20 mg ) were compared in 402 patients with primary hypercholesterolemia with and without documented coronary heart disease or peripheral vascular disease . After 8 weeks of treatment , cerivastatin provided significantly greater reductions than pravastatin in low-density lipoprotein (LDL)-cholesterol ( 31.1 % vs. 26.0 % ; p < 0.0001 ) and total cholesterol ( 21.1 % vs. 17.8 % ; p < 0.0001 ) . A greater proportion of patients treated with cerivastatin than pravastatin achieved > 30 % and > 40 % reductions from baseline in LDL-cholesterol . Both agents also increased high density lipoprotein-cholesterol and reduced triglycerides . Overall , 65.1 % of patients treated with cerivastatin and 63.3 % of patients with pravastatin achieved LDL-cholesterol goals defined by the National Cholesterol Education Program . Both drugs were well tolerated , with most adverse events being mild . These results demonstrate that cerivastatin ( 0.3 mg ) is a highly effective 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor , which enables a large proportion of patients to achieve clinical ly meaningful reductions in LDL-cholesterol The Probucol Quantitative Regression Swedish Trial ( PQRST ) investigated the effect of the lipid lowering and antioxidant drug probucol on the development of atherosclerosis in humans . 303 hypercholesterolemic patients were r and omized to receive either probucol or placebo , in combination with dietary advice and cholestyramine for a three-year period . Probucol was not found to effect progression regression of femoral atherosclerosis significantly as assessed by quantitative arteriography . To evaluate the effectiveness of probucol as an antioxidant during the study period , detailed analyses were performed on 42 of the r and omized patients . During the trial , probucol-treated patients ( n = 26 ) had 15 % lower total cholesterol ( P < 0.01 ) and 35 % lower high density lipoprotein ( HDL ) cholesterol ( P < 0.0001 ) compared with controls ( n = 16 ) . Low density lipoprotein ( LDL ) from probucol treated individuals was more resistant to oxidation by Cu2 + as determined by the lag phase for the formation of conjugated dienes ( 220 + /- 8 vs. 82 + /- 7 min ( mean + /- S.E ) ) , showed a 13 times lower formation of lipid peroxides , a 97 % reduction in macrophage degradation and close to 90 % less decrease in LDL receptor binding following oxidation as compared with controls ( P < 0.001 for all differences ) . The results demonstrate that although probucol provided a significant protection against Cu(2+)-induced oxidative modification of LDL , it lacked effect on the development of femoral atherosclerosis . The relevance of these observations for the proposed role of lipid oxidation in atherosclerosis is discussed This double-blind study was design ed to examine and compare the effects of supplementing the existing diet with fish oil or olive oil on lipids and cell function in patients with peripheral vascular disease . Thirty-two patients with symptomatic and angiographically demonstrated peripheral vascular disease were screened , matched , and r and omly allocated to take either 15 g/d fish oil or olive oil for 4 weeks . Fish oil reduced serum triglyceride levels by 26 % , but increased total cholesterol levels due to a significant increase in both low-density lipoprotein cholesterol ( LDL-C ) and high-density lipoprotein-2 cholesterol ( HDL2-C ) . There was a nonsignificant decrease in HDL3-C levels .  Olive oil reduced total cholesterol levels , accountable to a significantly decrease in LDL-C levels . Serum thromboxane B2 ( TXB2 ) levels remained unchanged following fish oil , but were significantly increased by olive oil .  Urinary excretion of TXB2 and 6-keto-PGF1 alpha was unaffected by either oil supplement . Platelet aggregation , which was measured in platelet-rich plasma in response to two doses of collagen or platelet-activating factor ( PAF ) , was significantly reduced after fish oil , but was increased by olive oil . Following fish oil , there was a significant increase in eicosapentaenoic acid ( EPA , 20:5 ) and docosahexaenoic acid ( DHA , 22:6 ) levels and a decrease in arachidonic acid content of platelet phospholipids . The platelet fatty acid composition after olive oil was unchanged . Fish oil decreased neutrophil leukotriene B4 ( LTB4 ) generation following calcium ionophore stimulation by 33 % , while leukotriene B5 levels increased significantly . Neutrophil PAF production and plasma lyso-PAF were unaffected by either oil . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of the double-blind , crossover , placebo-controlled study was to evaluate whether oral administration of sulodexide , a medium molecular weight glycosaminoglycan , had an effect on whole blood , plasma and serum viscosity , and /or plasma fibrinogen concentrations . The drug was administered orally at a dose of 500 lipoproteinlipase releasing units twice daily for 1 month to two groups of 20 patients with peripheral vascular disease ; one group was administered a placebo – drug sequence and the other a drug – placebo sequence .  Orally administered sulodexide had a marked effect on plasma viscosity and on plasma fibrinogen concentrations , whereas there were no effects on whole blood viscosity . No significant side-effects were observed . The fact that sulodexide was highly effective , even after oral administration , suggests it may be useful for the treatment of patients with atheromatous vascular diseases of the lower limbs requiring chronic therapy The Heart Protection Study ( HPS ) , with over 20,500 subjects , is the largest trial of statin therapy ever conducted . It provides important and definitive new information on women , the elderly , diabetics , and people with low baseline cholesterol pre-treatment and those with prior occlusive non-coronary vascular disease . It is a prospect i ve double blind r and omised controlled trial with a 2 x 2 factorial design investigating prolonged use ( > 5 years ) of simvastatin 40 mg and a cocktail of antioxidant vitamins ( 650 mg vitamin E , 250 mg vitamin C and 20 mg beta-carotene ) . The HPS specifically included patients with high risk for coronary heart disease ( CHD ) but characteristics that excluded them from participation in previous statin trials .  Simvastatin 40 mg treatment showed benefit across all patient groups regardless of age , gender or baseline cholesterol value and proved safe and well tolerated . Results show a 12 % reduction in total mortality , a 17 % reduction in vascular mortality , a 24 % reduction in CHD events , a 27 % reduction in all strokes and a 16 % reduction in non-coronary revascularisations . Among high-risk patients in this western population ( with a minimum total cholesterol [ TC ] > or = 3.5 mmol/l at entry ) there appears to be no threshold cholesterol value below which statin therapy is not associated with benefit ; even among those with pre-treatment cholesterol levels below current national recommended targets . Over the 5.5 year study period patients and their doctors were encouraged to add an active non- study statin to the study regimen if they wished to do so . Thus the trial eventually had only two-thirds complying with the original intention-to-treat design . Nevertheless , results were highly significant for the study statin -- simvastatin 40 mg once daily . Preliminary results of the HPS are negative for the antioxidant vitamin cocktail but provide reassurance that vitamins do no harm This study demonstrates that niacin supplementation decreases plasma fibrinogen and low-density lipoprotein cholesterol in subjects with peripheral vascular disease r and omized to receive niacin , warfarin , antioxidants , or placebo . Changes in fibrinogen levels are highly correlated with changes in low-density lipoprotein cholesterol ( r = 0.61 ; p < 0.009 ) in subjects taking niacin The Cholesterol-Lowering Atherosclerosis Study ( CLAS ) was a r and omized , placebo-controlled , angiographic trial testing combined colestipol hydrochloride and niacin therapy in 162 nonsmoking men aged 40 to 59 years with previous coronary bypass surgery . During two years of treatment there was a 26 % reduction in total plasma cholesterol , a 43 % reduction in low-density lipoprotein cholesterol , plus a simultaneous 37 % elevation of high-density lipoprotein cholesterol . This result ed in a significant reduction in the average number of lesions per subject that progressed ( P less than .03 ) and the percentage of subjects with new atheroma formation ( P less than .03 ) in native coronary arteries . Also , the percentage of subjects with new lesions ( P less than .04 ) or any adverse change in bypass grafts ( P less than .03 ) was significantly reduced . Deterioration in overall coronary status was significantly less in drug-treated subjects than placebo-treated subjects ( P less than .001 ) . Atherosclerosis regression , as indicated by perceptible improvement in overall coronary status , occurred in 16.2 % of colestipol-niacin treated vs 2.4 % placebo treated ( P = .002 ) Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects . The present study was undertaken to compare the effects of policosanol and lovastatin on patients with moderately severe intermittent claudication . The study had a 4-week baseline step , followed by a 20-week double blinded , r and omized treatment period . Twenty-eight patients who met study entry criteria were r and omized to policosanol 10 mg or lovastatin 20 mg tablets once daily  . Walking distances in a treadmill ( constant speed 3.2 km/hr , slope 10 ° , temperature 25 ° C ) were assessed before and after 20 weeks of treatment . Both groups were similar at r and om ization . Compared with baseline , policosanol increased significantly ( p<0.01 ) the initial claudi cation distance ( ICD ) from 160.39 ±15.82 m to 211.31 ±21.48 m ( + 33.7 % ) and the absolute claudication distance ( ACD ) ( p<0.001 ) from 236.39 ±25.44 m to 288.09 ±28.47 m ( + 24.3 % ) ; meanwhile both variables remained unchanged after lovastatin  therapy . Changes in ICD and ACD were significantly larger in the policosanol than in the lovastatin group ( p<0.01 ) . Policosanol , but not lovastatin , significantly increased ( p < 0.05 ) the ankle/arm index , although between-group differences were not significant . The frequency of patients reporting improve ment on quality of life domains was greater in the policosanol than in the lovastatin group . Policosanol significantly ( p < 0.00 1 ) lowered total cholesterol ( TC ) and low-density lipoprotein- cholesterol ( LDL-C ) by 17.5 % and 31.0 % , respectively , and meanwhile increased ( p<0.01 ) high- density lipoprotein-cholesterol ( HDL-C ) levels by 31.5 % . Lovastatin  reduced ( p<0.01 ) TC ( 18.0 % ) , LDL-C ( 22.6 % ) , and ( p<0.05 ) triglycerides ( 9.8 % ) . In addition , policosanol , but not lovastatin , moderately , but significantly , reduced ( p < 0.05 ) fibrinogen levels , so that final values and percent changes in both groups were different ( p<0.01 ) . Treatments were well tolerated . Only 1 lovastatin patient withdrew from the study because of a nonfatal myocardial infa rct ion . Five lovastatin patients , but none from the policosanol group , experienced 6 adverse events ( AE ) ( p<0.01 ) . The present results indicate that policosanol , but not lovastatin , is a suitable alternative to manage patients with intermittent claudication  because of pleiotropic properties beyond its cholesterol-lowering effects Two types of end-point measurement are presently available in clinical trials of the effect of treatment of hyperlipidaemia on cardiovascular disease ; these are the incidence of clinical events and the arteriographic assessment of progression or regression of atherosclerosis . These approaches are briefly review ed . In the present trial , 25 hyperlipidaemic men with symptomatic femoral atherosclerosis underwent biplanar femoral arteriography at baseline .  They were then r and omised into treatment and usual-care groups ; treatment was individualized , comprising a lipid-lowering diet with cholestyramine , nicotinic acid or clofibrate as appropriate for the lipoprotein disorder . Mean cholesterol and triglyceride levels were 19 % and 37 % lower in the treatment group . Arteriography was repeated after a mean period of 19 months . With attention to blinding of observers , changes in arteriograms were quantitated using computerised image analysis and visual methods , and expressed both by patient and by arterial segment . All end-points were in conformity and showed a lower rate of progression of arterial disease in the treatment group , and a higher frequency of segmental regression in treated patients . In this small trial of patients with functionally-significant atherosclerosis , effective treatment of hyperlipidaemia favourably affected the course of the arterial disease Thirty patients with Stage II peripheral vascular disease were treated with sulodexide , a new , medium molecular weight glycosaminoglycan , and placebo using a double-blind , crossover study design . After a 1-month wash-out period , patients were treated for 1 month with one or other trial medication and then crossed over to the alternative preparation for a further month . Measurements were made at baseline and at the end of each treatment period of serum , plasma and whole blood viscosities ( at various shear rates ) , fibrinogen levels and red cell filterability . Tolerance parameters were also assessed at the same times . The results showed that there were statistically significant reductions in plasma and whole blood viscosity and in fibrinogen levels after sulodexide , but not after placebo . Neither treatment had any marked effect on red blood cell filterability . Local and systemic tolerance of the treatment was excellent , and some patients reported an improvement in symptoms whilst they were taking sulodexide ; this , however , could not be quantified in this study . It is suggested that the viscosity and fibrinogen reducing effect of sulodexide make it a useful form of treatment in patients with atheromatous vascular diseases of the lower limbs CONTEXT Although niacin increases low levels of high-density lipoprotein cholesterol ( HDL-C ) , which frequently accompany diabetes , current guidelines do not recommend use of niacin in patients with diabetes because of concerns about adverse effects on glycemic control ; however , this is based on limited clinical data . OBJECTIVE To determine the efficacy and safety of lipid-modifying dosages of niacin in patients with diabetes . DESIGN AND SETTING Prospect i ve , r and omized placebo-controlled clinical trial conducted in 6 clinical centers from August 1993 to December 1995 . PARTICIPANTS A total of 468 participants , including 125 with diabetes , who had diagnosed peripheral arterial disease . INTERVENTIONS After an active run-in period , participants were r and omly assigned to receive niacin ( crystalline nicotinic acid ) , 3000 mg/d or maximum tolerated dosage ( n = 64 with diabetes ; n = 173 without diabetes ) , or placebo ( n = 61 with diabetes ; n = 170 without diabetes ) for up to 60 weeks ( 12-week active run-in and 48-week double-blind ) . MAIN OUTCOME MEASURES Plasma lipoprotein , glucose , hemoglobin A(1c ) ( HbA(1c ) ) , alanine aminotransferase , and uric acid levels ; hypoglycemic drug use ; compliance ; and adverse events , in patients with diabetes vs without who were receiving niacin vs placebo . RESULTS Niacin use significantly increased HDL-C by 29 % and 29 % and decreased triglycerides by 23 % and 28 % and low-density lipoprotein cholesterol ( LDL-C ) by 8 % and 9 % , respectively , in participants with and without diabetes ( P<.001 for niacin vs placebo for all ) . Corresponding changes in participants receiving placebo were increases of 0 % and 2 % in HDL-C and increases of 7 % and 0 % in triglycerides , and increases of 1 % and 1 % in LDL-C. Glucose levels were modestly increased by niacin ( 8.7 and 6.3 mg/dL [ 0.4 and 0.3 mmol/L ] ; P = .04 and P<.001 ) in participants with and without diabetes , respectively . Levels of HbA(1c ) were unchanged from baseline to follow-up in participants with diabetes treated with niacin . In participants with diabetes treated with placebo , HbA(1c ) decreased by 0.3 % ( P = .04 for difference ) . There were no significant differences in niacin discontinuation , niacin dosage , or hypoglycemic therapy in participants with diabetes assigned to niacin vs placebo . CONCLUSIONS Our study suggests that lipid-modifying dosages of niacin can be safely used in patients with diabetes and that niacin therapy may be considered as an alternative to statin drugs or fibrates for patients with diabetes in whom these agents are not tolerated or fail to sufficiently correct hypertriglyceridemia or low HDL-C levels .  JAMA . 2000;284:1263 - Increased blood viscosity occurs in patients with claudication . This increase in viscosity , which is mainly due to elevated fibrinogen levels and a decreased red cell deformability , adversely influences blood flow . In addition to a positive effect on blood pressure , blood lipids , and platelet responsiveness , fish oil may improve blood flow due to a favorable influence on hemorrheology . In a prospect i ve , r and omized , double-blind study , we evaluated the effect of six capsules of fish oil ( 1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid ) versus six capsules of corn oil ( 3 g linoleic acid ) , administered for 4 months , on walking distances , pressure indices during rest and after exercise , blood pressure , red cell deformability , fibrinogen , and lipid levels in 32 patients with stable claudication . No significant changes in walking distances and pressure indices during rest and after exercise occurred , despite a significant increase in red cell deformability in the fish oil group . Fibrinogen levels did not change in either group . In the fish oil group , a favorable change in blood lipids was noted ; high-density cholesterol increased and triglycerides decreased . Mean arterial blood pressure declined to a similar extent in both groups . Thus , short-term supplementation with fish oil does not lead to clinical ly significant improvement of symptoms in patients with stable claudication . This suggests that red cell deformability is of minor importance in the arterial blood flow in the legs of these patients BACKGROUND In patients with high cholesterol levels , lowering the cholesterol level reduces the risk of coronary events , but the effect of lowering cholesterol levels in the majority of patients with coronary disease , who have average levels , is less clear . METHODS In a double-blind trial lasting five years we administered either 40 mg of pravastatin per day or placebo to 4159 patients ( 3583 men and 576 women ) with myocardial infa rct ion who had plasma total cholesterol levels below 240 mg per deciliter ( mean , 209 ) and low-density lipoprotein ( LDL ) cholesterol levels of 115 to 174 mg per deciliter ( mean , 139 ) . The primary end point was a fatal coronary event or a nonfatal myocardial infa rct ion . RESULTS The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group , an absolute difference of 3 percentage points and a 24 percent reduction in risk ( 95 percent confidence interval , 9 to 36 percent ; P = 0.003 ) . Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group , a 26 percent reduction ( P=0.005 ) , and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group , a 23 percent reduction ( P=0.01 ) . The frequency of stroke was reduced by 31 percent ( P=0.03 ) . There were no significant differences in overall mortality or mortality from noncardiovascular causes . Pravastatin lowered the rate of coronary events more among women than among men . The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol . CONCLUSIONS These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels BACKGROUND In patients with coronary heart disease and a broad range of cholesterol levels , cholesterol-lowering therapy reduces the risk of coronary events , but the effects on mortality from coronary heart disease and overall mortality have remained uncertain . METHODS In a double-blind , r and omized trial , we compared the effects of pravastatin ( 40 mg daily ) with those of a placebo over a mean follow-up period of 6.1 years in 9014 patients who were 31 to 75 years of age . The patients had a history of myocardial infa rct ion or hospitalization for unstable angina and initial plasma total cholesterol levels of 155 to 271 mg per deciliter . Both groups received advice on following a cholesterol-lowering diet . The primary study outcome was mortality from coronary heart disease . RESULTS Death from coronary heart disease occurred in 8.3 percent of the patients in the placebo group and 6.4 percent of those in the pravastatin group , a relative reduction in risk of 24 percent ( 95 percent confidence interval , 12 to 35 percent ; P<0.001 ) . Overall mortality was 14.1 percent in the placebo group and 11.0 percent in the pravastatin group ( relative reduction in risk , 22 percent ; 95 percent confidence interval , 13 to 31 percent ; P<0.001 ) . The incidence of all cardiovascular outcomes was consistently lower among patients assigned to receive pravastatin ; these outcomes included myocardial infa rct ion ( reduction in risk , 29 percent ; P<0.001 ) , death from coronary heart disease or nonfatal myocardial infa rct ion ( a 24 percent reduction in risk , P<0.001 ) , stroke ( a 19 percent reduction in risk , P=0.048 ) , and coronary revascularization ( a 20 percent reduction in risk , P<0.001 ) . The effects of treatment were similar for all predefined subgroups . There were no clinical ly significant adverse effects of treatment with pravastatin . CONCLUSIONS Pravastatin therapy reduced mortality from coronary heart disease and overall mortality , as compared with the rates in the placebo group , as well as the incidence of all prespecified cardiovascular events in patients with a history of myocardial infa rct ion or unstable angina who had a broad range of initial cholesterol levels Purpose : To evaluate the effect of probucol and /or of endovascular brachytherapy ( EVBT ) on restenosis after percutaneous transluminal angioplasty ( PTA ) of femoropopliteal arteries . Methods : A total of 335 patients ( 206 men ; mean age 72±9 years ) with intermittent claudication were r and omized according to a 2 × 2 factorial design to 1 of the 4 groups : probucol , placebo , EVBT , and EVBT+probucol . Probucol ( 1 g/d ) or placebo were given in double-blinded fashion 1 month before and for 6 months after PTA . Gamma irradiation ( 192Iridium , 14 Gy , 5-mm reference depth ) was r and omly applied in an unblinded manner from a noncentered endoluminal catheter . All patients received aspirin ( 100 mg/d ) . Primary endpoint was restenosis ( > 50 % diameter reduction ) detected by duplex ultrasound 6 months after PTA . Secondary endpoints included clinical and hemodynamic assessment . Results : Restenosis in patients undergoing EVBT was 17 % ( 23/133 ) versus 35 % ( 50/142 ) in patients without EVBT ( p<0.001 ) ; in patients treated with probucol versus placebo , the rates were 23 % ( 31/135 ) and 30 % ( 43/140 , p<0.001 ) . Three quarters ( 77 % , 102/133 ) of patients were free of claudication after EVBT therapy versus 61 % ( 87/142 ) without EVBT ( p<0.05 ) . Need for target vessel revascularization was 6 % ( 8/133 ) with EVBT versus 14 % ( 20/142 ) without EVBT ( p<0.01 ) . Late thrombotic occlusions occurred in 4 % ( 6/133 ) , exclusively in patients treated with EVBT after stent implantation . Conclusions : Endovascular brachytherapy significantly reduces restenosis , improves symptoms , and reduces re interventions after PTA of femoropopliteal arteries . Probucol reduces restenosis but has no additive effect when combined with brachytherapy OBJECTIVES This study compared the efficacy and safety of atorvastatin , fluvastatin , lovastatin , and simvastatin in patients with documented atherosclerosis treated to U.S. National Cholesterol Education Program ( NCEP ) recommended low-density-lipoprotein ( LDL ) cholesterol concentration ( < or = 100 mg/dl [ 2.59 mmol/liter ] ) . BACKGROUND For patients with advanced atherosclerosis , NCEP recommends lipid-lowering drug therapy if LDL cholesterol remains > or = 130 mg/dl ( 3.36 mmol/liter ) . METHODS A total of 318 men or women with documented atherosclerosis and LDL cholesterol > or = 130 mg/dl ( 3.36 mmol/liter ) and < or = 250 mg/dl ( 6.5 mmol/liter ) , and triglycerides < or = 400 mg/dl ( 4.5 mmol/liter ) participated in this 54-week , multicenter , open-label , r and omized , parallel-group , active-controlled , treat-to-target study . Patients were titrated at 12-week intervals until the LDL cholesterol goal was reached . Number of patients reaching target LDL cholesterol levels and dose to reach target were evaluated . RESULTS At the starting doses , atorvastatin 10 mg produced significantly greater decreases ( p < 0.05 ) in plasma LDL cholesterol than the other treatments . Subsequently , the percentage of patients reaching goal at the starting dose was 32 % for atorvastatin , 1 % for fluvastatin , 10 % for lovastatin and 22 % for simvastatin . Atorvastatin-treated patients required a lower median dose than other treatments . Median doses at week 54 with the last available visit carried forward were atorvastatin 20 mg/day , fluvastatin 40 mg/day + colestipol 20 g/day , lovastatin 80 mg/day , simvastatin 40 mg/day . CONCLUSIONS A significantly greater number ( p < 0.05 ) of patients with confirmed atherosclerosis treated with atorvastatin reached the target LDL cholesterol concentration at the starting dose than patients treated with fluvastatin or lovastatin , and significantly fewer ( p < 0.05 ) patients treated with atorvastatin required combination therapy with colestipol to achieve target LDL cholesterol concentrations than all other statins tested BACKGROUND Previous health economic studies have demonstrated the cost-effectiveness of simvastatin in the treatment of coronary heart disease ( CHD ) based on clinical results of the Sc and inavian Simvastatin Survival Study . A prior analysis evaluated the " cost of getting to goal , " but ignored all costs after titration . However , when evaluating the cost-effectiveness of long-term therapies , it is important to consider the maintenance costs as well . OBJECTIVE The purpose of this study was to evaluate the maintenance costs of treatment with simvastatin versus that of treatment with another more recently available statin , atorvastatin , in a European context . METHODS We assessed the long-term maintenance cost of simvastatin versus atorvastatin in terms of the cost of reducing low-density lipoprotein cholesterol ( LDL-C ) levels to the recommended goals based on a previously published clinical trial in patients with CHD . The analysis focused on the patients in the original clinical trial who were r and omized to treatment with simvastatin or atorvastatin . Patients began therapy with 10 mg of simvastatin or atorvastatin ;  the dose of study drug was titrated every 12 weeks up to 40 mg simvastatin or 80 mg atorvastatin , with the addition of up to 8 g/d of cholestyramine until a modified European Atherosclerosis Society LDL-C goal ( < 2.84 mmol/L ) was reached . As there was no significant difference between the 2 groups in re source utilization for adverse events , only drug costs were included . The calculated average annual maintenance cost was based on the distribution of the final daily dosing regimens and the public drug prices for each regimen . Individual country analyses were conducted using each local currency . RESULTS There was no significant difference between groups in the percentage of patients reaching their LDL-C goal over the study period ( 80 % for simvastatin-treated  pa- tients vs 89 % for atorvastatin-treated  patients , P = 0.135 ) . However , the cost of maintaining a similar percentage of patients at their appropriate LDL-C levels was significantly lower in the  simvastatin group compared with the atorvastatin group in 13 of the 17 countries assessed . In the remaining 4 countries , there was a cost advantage for simvastatin , but it did not reach statistical significance . CONCLUSIONS Across Europe there was a significant reduction in the cost of maintaining patients at their appropriate LDL-C levels with simvastatin versus atorvastatin . The results of this analysis , along with the proven clinical benefits of simvastatin , support the use of this drug as the treatment of choice in the secondary prevention of CHD Thirty patients suffering from peripheral vascular disease ( stage – II according to Fontaine ) were included in a double-blind study aim ed at assessing the efficacy of a high-dose glycosaminoglycan ( GAG ) ( Sulodexide ) both in terms of laboratory parameters , such as lipid metabolism and blood coagulation components , and instrumental procedures ( strain-gauge plethysmography ) . Compared with the fifteen control patients ( treated with placebo ) , the fifteen patients treated with Sulodexide showed a signficant decrease in blood triglycerides and fibrinogen as well as a significantly increased HDL-cholesterol , and positive instrumental changes : at the end of treatment Peak and Rest Flow values – and consequently also Winsor 's index – were significantly increased only in patients treated with Sulodexide This study was undertaken to evaluate the efficacy and tolerability of policosanol , a new cholesterol-lowering drug with concomitant antiplatelet effects , in patients with inter mittent claudication . After a baseline period of 6 weeks , 62 patients were r and omized to receive , under double-blind conditions , either placebo ( 31 patients ) or policosanol ( 31 ) , 10 mg twice daily . Walking distances in a treadmill ( constant speed 3.2 km/hr , slope 10 ° ) were assessed before and after 6 months of treatment . Both groups were similar at r and omization . Policosanol increased significantly ( p<0.01 ) the initial claudication distance from 132.5 ±13.5 m ( baseline ) to 205.7 ±36.3 m ( after therapy ) and the absolute claudication distance ( p<0.0001 ) from 229.5 ±22.0 m to 365.4 _ ±46.9 m ; meanwhile both variables remained unchanged in the placebo group ( p<0.05 ) . The reduction of lower limb symptoms showed a greater benefit in the policosanol group . There was no significant change in either group in the ankle/arm pressure ratio . The treatment was well tolerated . There were 10 discontinuations ( seven placebo , three poli- cosanol ) from the study . Six withdrawals occurred because of adverse events ( AE ) ; all were in placebo patients . There were five serious vascular AEs in the placebo group but none in the policosanol group ( p<0.05 ) . Overall , 12/31 ( 38.7 % ) placebo patients and 3/31 ( 9.7 % ) policosanol patients experienced AEs after r and omization , which showed a lesser incidence of AEs in the policosanol group ( p<0.01 ) . The present study demon strates a beneficial effect of policosanol in patients with intermittent claudication At sites of thrombosis and vascular injury , interactions occur among platelets , leucocytes and endothelial cells . Patients with peripheral arterial occlusive disease ( PAOD ) have been shown to have raised total serum cholesterol and serum triglycerides and increased sP-selectin levels when compared with controls . A total of 31 patients with PAOD and hypercholesterolaemia took part in this three-staged study . Soluble P-selectin ( sP-selectin ) levels were significantly lowered after 12 weeks of fluvastatin treatment ( 157.0 ng/ml versus 113.77 ng/ml , p = 0.01 ) , whereas 12 weeks of placebo treatment had no statistically significant effect on sP-selectin levels ( 150.0 ng/ml versus 139.4 ng/ml ) . An unpaired t-test almost reached statistical significance ( p = 0.051 ) when the levels by which sP-selectin fell after 12 weeks of active or placebo treatment were compared . The placebo group was then put onto long-term , active treatment and sP-selectin levels were significantly lowered by fluvastatin when compared to pre-treatment levels ( 150.0 ng/ml versus 110.0 ng/ml , p = 0.03 ) . By lowering the levels of P-selectin , fluvastatin may not only attenuate atherosclerotic progression but may also decrease the platelet activation associated with PAOD The effect of probucol on the development of atherosclerosis is being investigated in the Probucol Quantitative Regression Swedish Trial ( PQRST ) . Hypercholesterolemic patients are r and omized to receive either probucol 0.5 g twice daily or placebo in a double-blind manner , in combination with dietary therapy and cholestyramine 8 - 16 g daily for a 3-year period . The primary endpoint of the trial is the change in atheroma volume , assessed by annual quantitative angiography involving 20-cm segments of the femoral artery . Data from the open diet and prer and omization phase indicate that probucol added to dietary intervention plus cholestyramine produced highly significant reductions in total ( -17 % ) , low-density lipoprotein ( LDL ; -10 % ) , and high-density lipoprotein ( -30 % ) cholesterol . From a sub population , LDL levels were isolated during different stages of the prer and omization phase . LDL was exposed to the oxidant Cu2 + and binding to fibroblasts as well as degradation by macrophages was measured . The generation of thiobarbituric acid-reactive substances ( TBARS ) was also measured . Probucol prevented degradation of copper-exposed LDL by macrophages and also reduced the formation of TBARS , indicating that probucol protected LDL from oxidation . After the trial concludes in December 1992 , statistical models will be used to investigate how much of the change in atherosclerosis is explained by changes in lipoprotein concentrations and how much is explained by probucol 's antioxidative effects . Thus , other metabolic factors such as dietary intake and circulating levels of lipid soluble vitamins and fatty acids that may modify the possible antioxidative effects of probucol are also measured and will be related to change in atherosclerosis The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery .  Probucol is combined with cholestyramine and dietary management in  hypercholesterolemic patients , and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique . A r and omly selected control group is also being managed by dietary therapy and cholestyramine , but receives placebo instead of probucol . The treatment time in this double-blind trial is 3 years , and femoral angiography is performed yearly . Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals . The basic study design is described here , and some results from the open prer and omization phase of the study are presented BACKGROUND Individuals with diabetes are at increased risk of cardiovascular morbidity and mortality , although typically their plasma concentrations of LDL cholesterol are similar to those in the general population . Previous evidence about the effects of lowering cholesterol in people with diabetes has been limited , and most diabetic patients do not currently receive cholesterol-lowering therapy despite their increased risk . METHODS 5963 UK adults ( aged 40 - 80 years ) known to have diabetes , and an additional 14573 with occlusive arterial disease ( but no diagnosed diabetes ) , were r and omly allocated to receive 40 mg simvastatin daily or matching placebo . Prespecified analyses in these prior disease subcategories , and other relevant subcategories , were of first major coronary event ( ie , non-fatal myocardial infa rct ion or coronary death ) and of first major vascular event ( ie , major coronary event , stroke or revascularisation ) . Analyses were also conducted of subsequent vascular events during the scheduled treatment period . Comparisons are of all simvastatin-allocated versus all placebo-allocated participants ( ie , intention to treat ) , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( 39 mg/dL ) during the 5-year treatment period . FINDINGS Both among the participants who presented with diabetes and among those who did not , there were highly significant reductions of about a quarter in the first event rate for major coronary events , for strokes , and for revascularisations . For the first occurrence of any of these major vascular events among participants with diabetes , there was a definite 22 % ( 95 % CI 13 - 30 ) reduction in the event rate ( 601 [ 20.2 % ] simvastatin-allocated vs 748 [ 25.1 % ] placebo-allocated , p<0.0001 ) , which was similar to that among the other high-risk individuals studied . There were also highly significant reductions of 33 % ( 95 % CI 17 - 46 , p=0.0003 ) among the 2912 diabetic participants who did not have any diagnosed occlusive arterial disease at entry , and of 27 % ( 95 % CI 13 - 40 , p=0.0007 ) among the 2426 diabetic participants whose pretreatment LDL cholesterol concentration was below 3.0 mmol/L ( 116 mg/dL ) . The proportional reduction in risk was also about a quarter among various other subcategories of diabetic patient studied , including : those with different duration , type , or control of diabetes ; those aged over 65 years at entry or with hypertension ; and those with total cholesterol below 5.0 mmol/L ( 193 mg/dL ) . In addition , among participants who had a first major vascular event following r and omisation , allocation to simvastatin reduced the rate of subsequent events during the scheduled treatment period . INTERPRETATION The present study provides direct evidence that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rate of first major vascular events by about a quarter in a wide range of diabetic patients studied . After making allowance for non-compliance , actual use of this statin regimen would probably reduce these rates by about a third . For example , among the type of diabetic patient studied without occlusive arterial disease , 5 years of treatment would be expected to prevent about 45 people per 1000 from having at least one major vascular event ( and , among these 45 people , to prevent about 70 first or subsequent events during this treatment period ) . Statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events  , irrespective of their initial cholesterol concentrations BACKGROUND & AIMS The aim of this study was to compare the in vivo effects of a diet rich in virgin olive oil or sunflower oil on the lipid profile and on LDL susceptibility to oxidative modification in free-living Spanish male patients with peripheral vascular disease . METHODS A total of 20 Spanish male subjects diagnosed with peripheral vascular disease were r and omly divided into two groups ( n = 10 ) receiving different supplements , virgin olive oil and sunflower oil for 4 months . RESULTS The adaptation of patients to the experimental supplements was demonstrated since plasma and LDL fatty acids composition reflected dietary fatty acids . No differences in triglycerides , total cholesterol , LDL-cholesterol or HDL-cholesterol concentrations were found between the groups of patients . A significantly higher LDL susceptibility to oxidation was observed after sunflower oil intake in comparison with virgin olive oil , in spite of an increase in LDL alpha-tocopherol concentration in sunflower oil group . CONCLUSIONS The results of the present study provide further evidence that sunflower-oil-enriched diets does not protect LDL against oxidation as virgin olive oil does in patients with peripheral vascular disease The Probucol Quantitative Regression Swedish Trial tested whether treatment of hypercholesterolemic persons with probucol for 3 years affected femoral atherosclerosis . The primary end point was the change in atheroma volume estimated as change in lumen volume of the femoral artery assessed by quantitative arteriography . Three hundred three patients with visible atherosclerosis were r and omized to probucol 0.5 g , twice daily , or to placebo . All patients were given diet and cholestyramine , 8 to 16 g/day . Twenty-nine patients were excluded because of inadequate primary end point measurements . The mean age of the remaining 274 subjects ( 158 were men ) was 55 years . Seventeen percent had intermittent claudication and 24 % had angina pectoris . After 3 years , the probucol-treated patients had 17 % lower serum cholesterol , 12 % lower low-density lipoprotein cholesterol , 24 % lower total high-density lipoprotein cholesterol , and 34 % lower high-density lipoprotein2 cholesterol levels than control subjects . All lipoprotein differences between the treatment groups remained highly significant during the trial . There was no statistically significant change in lumen volume between the probucol and the control group . Furthermore , there was no difference between the treatment groups with regard to change in arterial edge roughness or amount of aorto-femoral atherosclerosis ; neither were there any differences between the treatment groups with regard to change in ST-segment depressions on exercise tests or ankle/arm blood pressure ( secondary end points ) . In the control group , lumen volume increased ( p < 0.001 ) and roughness of the femoral artery decreased ( p < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects . This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication . The study consisted of a 6-week single-blind , placebo-controlled run in phase , followed by a 2-year double-blind , r and omized treatment step . Fifty-six patients who met study entry criteria were r and omized to receive placebo or poli cosanol 10 mg twice daily . Walking distances on a treadmill ( constant speed 3.2 km/h , slope 10 ° , temperature 25 ° C ) were assessed before and after 6 , 12 , 18 , and 24 months of treatment . Both groups were similar at r and omization . After 6 months of therapy , policosanol significantly increased ( p < 0.0 1 ) the initial claudication distance from 125.9 ±8.7 m to 201.1 ±24.8 m and the absolute claudication distance from 219.5 ± 14.1 m to 380.7 ±50.2 m. Both variables remained unchanged in the placebo group ( p<0.01 ) . These effects did not wear off but improved after long-term therapy , so that final values were 333.5 ±28.6 m ( initial claudication distance ) and 648.9 ±54.1 m ( absolute claudication distance ) ; both significantly greater ( p<0.0001 ) than those obtained in the placebo group , which showed values of 137.9 ±21.8 m ( initial claudication distance ) and 237.7 ±28.1 m ( absolute claudication distance ) , respectively . At study completion , 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50 % ( p < 0.001 ) . Policosanol , but not placebo , significantly increased the ankle/arm pressure index . In addition , from month 6 up to study completion , the frequency of patients reporting improve ment of lower limb symptoms was greater in the policosanol group than in the placebo group . The treatment was tolerated well . There were 16 withdrawals ( 12 placebo , 4 policosanol ) from the study . Eight patients in the placebo group experienced a total of 10 serious adverse events , 8 of which were vascular events , compared with none in the policosanol group ( p<0.01 ) . In addition , 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study . The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication Abstract Forty-six patients with clinical ly significant peripheral atherosclerosis were r and omly allocated into two groups ; one receiving tablets of betapyridyl carbinol , up to 1800 mg daily , the other receiving a placebo . Patients were assessed clinical ly and their performance on a treadmill measured over intervals for two years . Plasma lipids were also measured . There was a slightly significant improvement in clinical findings after two years in those receiving drug treatment but no difference in symptoms . Treadmill performance appeared to improve equally in both placebo and drug treated groups . The plasma cholesterol fell significantly in the treated group compared the controls but the plasma triglycerides were not altered . Drop-outs from the trial did not differ significantly between the two groups . Two cases of hepatocellular dysfunction were attributable to betapyridyl carbinol BACKGROUND Patients with peripheral arterial disease ( PAD ) are at an increased risk of cardiovascular mortality and morbidity and thus are an excellent group in whom to evaluate the feasibility and the effect of an aggressive multifactorial intervention on atherosclerotic vascular disease risk factors . The Arterial Disease Multiple Intervention Trial ( ADMIT ) was design ed to determine the efficacy , safety , and compliance of an multifactorial therapy on selected atherosclerotic disease risk factors in patients with PAD . METHODS By a 2 x 2 x 2 factorial design , eligible participants ( N = 468 ) were r and omly assigned to low-dose warfarin , antioxidant vitamins , and niacin or its corresponding placebo , and followed up for 1 year . All participants were encouraged to use aspirin . Pravastatin was added to the drug regimen for those who needed to reduce LDL cholesterol to recommended levels . RESULTS Niacin increased HDL cholesterol levels by 30 % , with the majority of effect achieved at a dosage of 500 mg twice daily . Warfarin had an anticoagulant effect . The antioxidant vitamins result ed in a significant increase in vitamin E , C , and beta-carotene plasma levels . Overall , compliance was high and few adverse effects were reported . CONCLUSIONS ADMIT demonstrates that it is both feasible and safe to modify multiple atherosclerotic disease risk factors effectively with intensive combination therapy in patients with PAD The effects of plasma lipid reduction on the progression of femoral atherosclerosis have been studied in 24 hyperlipidaemic patients with stable intermittent claudication . The patients were r and omized into treatment or ‘ usual‐care ’ groups , the former receiving lipid‐lowering therapy by diet and drugs , and the latter no such treatment . Biplanar femoral arteriography was performed before and after a mean period of 19 months . In the treatment group plasma total cholesterol was decreased by a mean of 25 per cent and plasma triglyceride by more than 40 per cent . Plasma lipids were unchanged in the usual‐care group . Significantly fewer arterial segments showed detectable progression in the treatment group ( P < 0·01 ) . In addition , the mean increment in plaque area ( mm2 per segment per year ) in the treatment group was only 34 per cent of that in the usual‐care group ( P = 0.06 ) A r and omized trial was performed to test the hypothesis that , among patients with peripheral vascular disease , no difference is achieved in the magnitude of the reduction in blood cholesterol levels as a result of advice which is provided by a dietitian and that which is provided by a diet fact sheet .  Fifty-nine patients were allocated at r and om either to a " dietitian " group ( n = 31 ) or to a " diet fact sheet " group ( n = 28 ) . Dietary advice which was provided by a dietitian involved two personal interviews ; the diet fact sheet was prepared by the NSW Department of Health . Twenty-two and 23 members of each group , respectively , returned for follow-up at three months . The mean cholesterol level fell by 8.5 % among the " dietitian " group but only by 1.9 % among the " diet fact sheet " group . The difference of 0.47 mmol/L in the total cholesterol level reduction between the two groups was statistically significant ( P = 0.02 ; 95 % confidence interval , -0.88 to -0.07 mmol/L ) . It appears that individual advice which is provided by a dietitian is more successful in leading to a reduction in blood cholesterol levels than is the administration of a diet fact sheet , even though this particular diet fact sheet appears to be excellent and is used widely . In view of the large numbers of patients and of persons in the population as a whole who would benefit from a reduction in blood cholesterol levels , and the expense of individual advice to be provided by a dietitian , explorations of cost-effective methods of providing dietary advice are needed BACKGROUND Statin therapy reduces the rates of heart attack , stroke , and revascularisation among a wide range of individuals . Reliable assessment of its cost-effectiveness in different circumstances is needed . METHODS 20,536 adults ( aged 40 - 80 years ) with vascular disease or diabetes were r and omly allocated 40 mg simvastatin daily ( 10,269 ) or placebo ( 10,267 ) for an average of 5 years . Comparisons were made of hospitalisation and statin costs ( 2001 UK prices ) during the scheduled treatment period between all simvastatin-allocated versus all placebo-allocated participants . Cost-effectiveness was estimated among different categories of participant . FINDINGS Allocation to simvastatin was associated with a highly significant 22 % ( 95 % CI 16 - 27 ; p<0.0001 ) proportional reduction in hospitalisation costs for all vascular events , with similar proportional reductions in every subcategory of participant studied . During an average of 5 years , estimated absolute reductions in vascular event costs per person allocated 40 mg simvastatin daily ranged from UK 847 pounds sterling ( SE 137 ) in the highest risk quintile studied to 264 pounds sterling ( 48 ) in the lowest . Mean excess cost of statin therapy among participants allocated simvastatin was 1497 pounds sterling ( 8) , with similar absolute increases in every subcategory . Costs of preventing a major vascular event with 40 mg simvastatin daily ranged from 4500 pounds sterling ( 95 % CI 2300 - 7400 ) among participants with a 42 % 5-year major vascular event rate to 31,100 pounds sterling ( 22,900 - 42,500 ) among those with a 12 % rate ( corresponding to 5-year major coronary event rates of 22 % and 4 % , respectively ) . INTERPRETATION Statin therapy is cost effective for a wider range of individuals with vascular disease or diabetes than previously recognised ( particularly with lower-priced generics ) . It would be appropriate to consider reducing the estimated level of vascular event risk at which statin therapy is recommended We report the results of a r and omized single-centre study design ed to assess the effects of simvastatin on blood lipids , blood biochemistry , haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study . Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were r and omized , following a 2-month placebo ' run-in ' period , to receive 40 mg daily simvastatin , 20 mg daily simvastatin or matching placebo .  Their mean age was 63 years , 85 % were male , 62 % had a history of prior myocardial infa rct ion ( MI ) , and the mean baseline total cholesterol was 7.0 mmol.l-1 . Median follow-up in the present report is 3.4 years . Eight weeks after r and omization , 40 mg daily simvastatin had reduced non-fasting total cholesterol by 29.2 % + /- 1.1 ( 2.03 + /- 0.08 mmol.l-1 ) and 20 mg daily simvastatin had reduced it by 26.8 % + /- 1.0 ( 1.87 + /- 0.07 mmol.l-1 ) . Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol ( 40.8 % + /- 1.6 and 38.2 % + /- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively ) , but simvastatin also reduced triglycerides substantially ( 19.0 % and 17.3 % ) and produced a small increase in HDL cholesterol ( 6.4 % and 4.8 % ) . These effects were largely sustained over the next 3 years , with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years ( 25.7 % + /- 1.9 reduction ) than did 20 mg daily simvastatin ( 22.2 % + /- 1.8 ) . There were no differences between the treatment groups in the numbers of reports of ' possible adverse effects ' of treatment or of a range of different symptoms or conditions ( including those related to sleep or mood ) recorded at regular clinic follow-up . Mean levels of alanine aminotransferase , aspartate aminotransferase and creatine kinase were slightly increased by treatment , but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels . A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo , with no difference in the numbers of patients with low platelet counts . In summary , the simvastatin regimens studied produced large sustained reductions in total cholesterol , LDL cholesterol and triglyceride and small increases in HDL cholesterol . They were well tolerated , with no evidence of serious side-effects during the first 3 years of this study . ( ABSTRACT TRUNCATED AT 400 WORDS In a one-year , double-blind clinical trial , 45 patients with peripheral vascular disease ( PVD ) were r and omly assigned to either the American Heart Association Hyperlipidemia Diet C ( n = 20 ) or a low-fat , high-fiber , complex carbohydrate diet similar to the Pritikin Maintenance Diet ( n = 25 ) . Vascular status and blood lipid levels were monitored at 0 , 2 , 4 , 6 , and 12 months . Walking distance increased significantly in both groups , with no difference between groups . No vascular parameters changed significantly , suggesting that increased walking distance was due to improved metabolic capacity of the muscle . A trend toward lower blood lipid values was observed , with no significant differences within or between groups . We conclude that while patients with PVD benefit from a program of diet and exercise , there is no apparent advantage to the more difficult complex carbohydrate diet Forty patients with hyperlipoproteinemia were followed 4 - 9.3 years by non-invasive tests of their lower extremity circulation .  Twenty-eight patients were treated by diet and /or drugs , and 12 patients were controls .  Although all patients had abnormal non-invasive tests , only 15 patients had intermittent claudication . Seven patients had improved circulation tests while 13 showed a deterioration in the tests ; 20 patients had no changes . The patients who showed improvement in tests had the highest incidence of intermittent claudication and the lowest average ankle to brachial artery systolic blood pressure index . Although treatment patients had a significant decrease in total cholesterol , triglycerides , and VLDL , no significant differences were found when the results of the circulation tests were analyzed according to treatment or control status of the patients , to abnormal lipid patterns , or , ignoring treatment status , to a decrease in lipids . The patients who showed a deterioration in tests had a significantly higher total cholesterol level at the beginning of , but not during , the study and did not significantly decrease their triglycerides . No significant changes occurred in HDL , LDL , or VLDL . This study presents a methodology for the long-term , non-invasive assessment of peripheral arterial disease and a pilot study for its application . Despite the small number of patients studied , the failure to demonstrate benefit would discourage a larger clinical trial of this treatment protocol BACKGROUND Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease . The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin  compared with placebo . Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels . METHODS The Arterial Disease Multiple Intervention Trial , a multicenter r and omized , placebo-controlled trial , examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease . RESULTS During the screening phase , titration of niacin dose from 100 mg to 1000 mg daily result ed in a 17 % increase in mean plasma homocyst(e)ine level from 13.1 + /- 4.4 micromol/L to 15.3 + /- 5.6 micromol/L ( P < .0001 ) . At 18 weeks after r and omization , there was an absolute 55 % increase from baseline in mean plasma homocyst(e)ine levels in the niacin group and a 7 % decrease in the placebo group ( P = .0001 ) . This difference remained statistically significant at the end of follow-up at 48 weeks . CONCLUSIONS Niacin substantially increased plasma homocyst(e)ine levels , which could potentially reduce the expected benefits of niacin associated with lipoprotein modification . However , plasma homocyst(e)ine levels can be decreased by folic acid supplementation . Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial BACKGROUND Lower blood cholesterol concentrations have consistently been found to be strongly associated with lower risks of coronary disease but not with lower risks of stroke . Despite this observation , previous r and omised trials had indicated that cholesterol-lowering statin therapy reduces the risk of stroke , but large-scale prospect i ve confirmation has been needed . METHODS 3280 adults with cerebrovascular disease , and an additional 17256 with other occlusive arterial disease or diabetes , were r and omly allocated 40 mg simvastatin daily or matching placebo . Subgroup analyses were prespecified of first " major vascular event " ( ie , non-fatal myocardial infa rct ion or coronary death , stroke of any type , or any revascularisation procedure ) in prior disease subcategories . Subsidiary outcomes included any stroke , and stroke sub-type . Comparisons are of all simvastatin-allocated versus all placebo-allocated participants ( ie , " intention-to-treat " ) , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( 39 mg/dL ) during the 5-year treatment period . FINDINGS Overall , there was a highly significant 25 % ( 95 % CI 15 - 34 ) proportional reduction in the first event rate for stroke ( 444 [ 4.3 % ] simvastatin vs 585 [ 5.7 % ] placebo ; p<0.0001 ) , reflecting a definite 28 % ( 19 - 37 ) reduction in presumed ischaemic strokes ( p<0.0001 ) and no apparent difference in strokes attributed to haemorrhage ( 51 [ 0.5 % ] vs 53 [ 0.5 % ] ; rate ratio 0.95 [ 0.65 - 1.40 ] ; p=0.8 ) . In addition , simvastatin reduced the numbers having transient cerebral ischaemic attacks alone ( 2.0 % vs 2.4 % ; p=0.02 ) or requiring carotid endarterectomy or angioplasty ( 0.4 % vs 0.8 % ; p=0.0003 ) . The reduction in stroke was not significant during the first year , but was already significant ( p=0.0004 ) by the end of the second year . Among patients with pre-existing cerebrovascular disease there was no apparent reduction in the stroke rate , but there was a highly significant 20 % ( 8 - 29 ) reduction in the rate of any major vascular event ( 406 [ 24.7 % ] vs 488 [ 29.8 % ] ; p=0.001 ) . The proportional reductions in stroke were about one-quarter in each of the other subcategories of participant studied , including : those with coronary disease or diabetes ; those aged under or over 70 years at entry ; and those presenting with different levels of blood pressure or lipids ( even when the pretreatment LDL cholesterol was below 3.0 mmol/L [ 116 mg/dL ] ) . INTERPRETATION Much larger numbers of people in the present study suffered a stroke than in any previous cholesterol-lowering trial . The results demonstrate that statin therapy rapidly reduces the incidence not only of coronary events but also of ischaemic strokes , with no apparent effect on cerebral haemorrhage , even among individuals who do not have high cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rate of ischaemic strokes by about one-quarter and so , after making allowance for non-compliance in the trial , actual use of this regimen would probably reduce the stroke rate by about a third . HPS also provides definitive evidence that statin therapy is beneficial for people with pre-existing cerebrovascular disease , even if they do not already have manifest coronary disease In patients with advanced atherosclerosis manifested by arterial occlusion in the lower extremities without a baseline blood lipid disorder statin treatment caused improvement of the efficiency , i.e. prolongation of the claudication interval , while in a comparable control group without  statins the efficiency deteriorated further . In patients with arterial occlusion of the lower extremities with baseline dyslipidaemia  statin treatment proved protective , i.e. at least it retarded the patients ' complaints . The authors recorded improvement of the prooxidation state which followed after the dynamics of improvement of the impaired blood lipid spectrum . The results admit a possible part played by the pleiotropic effect of statins BACKGROUND Patients with peripheral arterial disease ( PAD ) have high rates of cardiovascular morbidity and mortality , including that caused by associated coronary heart disease and cerebrovascular disease . Previous studies have shown that coagulation parameters are altered in PAD and that altered coagulation may play a critical role in the susceptibility to cardiovascular complications in PAD . It is therefore important to assess the effect of secondary prevention measures on coagulation in patients with PAD . The Arterial Disease Multiple Intervention Trial ( ADMIT ) , a multicenter , r and omized , placebo-controlled trial , was conducted to determine the feasibility of a combined lipid-modifying , antioxidant , and antithrombotic treatment regimen in patients with PAD . The objective of this study was to assess the effect of the ADMIT interventions on coagulation . METHODS ADMIT participants were r and omly assigned to low-dose warfarin , niacin , and antioxidant vitamin cocktail or corresponding placebos in a 2 x 2 x 2 factorial design . Specialized coagulation studies were performed in a subset of 80 ADMIT participants at baseline and after 12 months of treatment . RESULTS Low-dose warfarin ( 1 to 4 mg/d ) result ed in a significant decrease in factor VIIc ( P < .001 ) and in plasma F1.2 ( P = .001 ) . Unexpectedly , niacin treatment also result ed in significant decrease in both fibrinogen ( 48 mg/dL ; P < .001 ) and F1.2 ( P = .04 ) . von Willebr and factor increased after antioxidant vitamin treatment ( P = .04 ) . CONCLUSIONS A regimen of low-dose warfarin effectively modifies coagulation in patients with PAD . Niacin also favorably modifies fibrinogen and plasma F1.2 . Niacin , in addition to its lipid effects , modifies abnormal coagulation factors that accompany PAD In a double-blind control of xanthinol nicotinate ( ' Complamin ' ; ' Complamex ' ) in patients with severe progressive obliterative vascular disease , 25 of 33 patients who completed the trial were helped significantly by the drug , as shown by both clinical and laboratory findings . Placebo helped in 4 of 33 patients . The difference is significant ( p less than 0 - 001 ) . These are the results for the trial period only . The results of follow-up for 6 to 30 months are available in 18 patients : 14 of these still had appreciable help from the drug , which was continued in maintenance doses . It should be noted that 3 of 6 diabetics were no longer helped after 6 months , and that only 3 of a total of 7 patients under the age of 50 were helped ; however 3 of the 4 not helped were diabetics under the age of 50 . Special caution was indicated in the use of the drug in patients who have ischaemic heart disease in addition to their peripheral arterial disease . Side-effects were common , particularly a severe prolonged flush shortly after taking a dose of the drug ; many patients helped by it accepted this side-effect if it occurred . Xanthinol nicotinate reduced whole-blood viscosity and cholesterol and fibrinogen in about half of the patients helped . This is a useful drug for about half the patients in whom surgery is not indicated or is contraindicated The effect of plasma lipid reduction on the progression of femoral atherosclerosis was studied in hyperlipidaemic patients with stable intermittent claudication . 24 patients were r and omly assigned to treatment and usual-care groups , the former receiving dietary advice and cholestyramine , nicotinic acid , or clofibrate depending on their lipoprotein phenotype . Biplanar arteriography was performed when the study began and after a mean period of 19 months . Angiograms were assessed visually , with blinding , and by computerised image analysis . Therapy reduced mean plasma total cholesterol by 25 % , mean low density lipoprotein ( LDL ) cholesterol by 28 % , and mean plasma triglycerides by 45 % . Significantly fewer arterial segments showed detectable progression of atherosclerosis in the treatment group . The mean increase in plaque area ( mm2/segment/year ) in the treatment group was only one third of that in the usual-care group . The mean increase in edge irregularity index ( a measure of the severity of disease ) in the treatment group was only 40 % of that in the usual care group . Twice as many arterial segments showed improvement in the treatment group . In both groups changes in edge irregularity index were directly related to plasma LDL cholesterol concentration . This study , the first r and omised controlled trial of its type , provides evidence that effective treatment of hyperlipidaemia favourably influences the natural history of symptomatic peripheral atherosclerosis
target: Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD .
  It may also improve local symptoms .
  Until further evidence on the relative effectiveness of different lipid-lowering agents is available , use of a statin in people with PAD and a blood cholesterol level > /=3.5 mmol/litre is most indicated
background: BACKGROUND Lipid-lowering therapy is recommended for secondary prevention in people with coronary artery disease .
  It may also reduce cardiovascular events and /or local disease progression in people with lower limb peripheral arterial disease ( PAD ) .
  OBJECTIVES To assess the effects of lipid-lowering therapy on all-cause mortality , cardiovascular events and local disease progression in patients with PAD of the lower limb .