***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Studies have shown that treatment of hyperlipidemia , especially lowering of plasma LDL levels , retards the progression of coronary atherosclerosis and prevents clinical cardiovascular events . No such studies have focused on subjects with low levels of HDL cholesterol . METHODS AND RESULTS We r and omly assigned 395 post-coronary bypass men , who had an HDL cholesterol concentration < or = 1.1 mmol/L and LDL cholesterol < or = 4.5 mmol/L , to receive gemfibrozil 1200 mg/d or placebo . Coronary angiography was performed at baseline and after , on average , 32 months of therapy . Changes in coronary dimensions were assessed by computer-assisted analysis . Average on-trial serum triglyceride concentrations were 1.69+/-0.68 and 1.02+/-0.37 , total cholesterol 5.48+/-0.68 and 4.83+/-0.63 , LDL cholesterol 3.84+/-0.59 and 3.39+/-0.56 , and HDL cholesterol 0.88+/-0.15 and 0.98+/-0.17 mmol/L in the placebo and gemfibrozil groups , respectively ( mean+/-SD , each P<.001 ) . The change in per-patient means of average diameters of native coronary segments was -0.04+/-0.11 mm in the placebo group and -0.01+/-0.10 mm in the gemfibrozil group ( P=.009 ) . The equivalent changes in minimum luminal diameters of stenoses were -0.09+/-0.18 and -0.04+/-0.15 mm , respectively ( P=.002 ) . A similar , albeit nonsignificant , trend toward treatment benefit was found in the predefined primary study end point , segments unaffected by grafts and those distal to graft insertions . In aortocoronary bypass grafts , 23 subjects ( 14 % ) assigned to placebo had new lesions in the follow-up angiogram , compared with 4 subjects ( 2 % ) assigned to gemfibrozil ( P<.001 ) . CONCLUSIONS Gemfibrozil therapy retarded the progression of coronary atherosclerosis and the formation of bypass-graft lesions after coronary bypass surgery in men with low HDL cholesterol as their main lipid abnormality Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p < 0.00001 ) , and the respective probabilities of escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p < 0.00001 ) in the risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients 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 A cooperative study in 20 Veterans Administration hospitals investigated the effect of clofibrate on morbidity and mortality due to atherosclerotic vascular disease in men with either an established cerebral infa rct ion or transient cerebrovascular ischemic attacks ( TIA ) . Follow-up observations were made for up to 4.5 years in 532 patients assigned on a r and om basis to placebo medication or to treatment with 2 gm of clofibrate daily . Baseline and follow-up cholesterol and triglyceride levels were measured . Recurrence of cerebral infa rct ion was increased in patients receiving clofibrate as compared to controls . The incidence of new myocardial infa rct ion and new TIA was similar in both groups . Despite the more frequent strokes in treated patients , they had a decrease in mortality , partially explained by a lower death rate from these recurrences . There was no correlation between pretreatment lipid ( cholesterol and triglyceride ) values and the result of therapy . Use of clofibrate , however , was associated with a slight reduction of cholesterol and a sustained fall in triglyceride . These findings do not support recently published reports that clofibrate reduces the occurrence of myocardial ischemia ; however , the investigative design and type of data collected in these various studies are different and make it difficult to compare results BACKGROUND Lipid-lowering secondary -prevention trials of coronary artery disease ( CAD ) have implicated triglyceride-rich lipoproteins as the main determinants of angiographic progression after elevated LDL cholesterol levels have been lowered with therapy . The present study focuses on the lipoprotein determinants of angiographic CAD progression in men with low HDL cholesterol concentration as their main baseline lipid abnormality who underwent 32 months of r and omized therapy with gemfibrozil or placebo .  METHODS AND RESULTS Men who had undergone coronary bypass surgery ( n=372 ) completed a r and omized , placebo-controlled study with gemfibrozil 1200 mg/d . They were selected primarily for HDL cholesterol levels that corresponded to the lowest third for middle-aged men . Average baseline lipid and lipoprotein levels were serum triglyceride , 1.60 ; serum cholesterol , 5.17 ; ultracentrifugally separated LDL cholesterol , 3.43 ; HDL2 cholesterol , 0.41 ; and HDL3 cholesterol , 0 . 61 mmol/L. In the gemfibrozil group , these levels were reduced on average by 40 % , 9 % , and 6 % or increased by 5 % and 9 % , respectively . On-trial IDL and LDL triglyceride and cholesterol levels significantly predicted global angiographic progression , taking into account changes in native segments and in bypass grafts . HDL3 but not HDL2 cholesterol concentration was associated with protection against progression , especially focal disease in native coronary lesions . VLDL was the lipoprotein most predictive of new lesions in vein grafts ; IDL was also significantly related . CONCLUSIONS This study exp and s the previous evidence of the triglyceride-rich lipoproteins , especially IDL , as predictors of angiographic progression of CAD but does not negate the significance of mildly elevated LDL levels . Of the HDL subfractions , only HDL3 was protective in this group of men selected for their low initial HDL levels BACKGROUND We investigated whether combination therapy with a statin plus a fibrate , as compared with statin monotherapy , would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease . METHODS We r and omly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo .  The primary outcome was the first occurrence of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS The annual rate of the primary outcome was 2.2 % in the fenofibrate group and 2.4 % in the placebo group ( hazard ratio in the fenofibrate group , 0.92 ; 95 % confidence interval [ CI ] , 0.79 to 1.08 ; P=0.32 ) . There were also no significant differences between the two study groups with respect to any secondary outcome . Annual rates of death were 1.5 % in the fenofibrate group and 1.6 % in the placebo group ( hazard ratio , 0.91 ; 95 % CI , 0.75 to 1.10 ; P=0.33 ) . Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex , with a benefit for men and possible harm for women ( P=0.01 for interaction ) , and a possible interaction according to lipid subgroup , with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol ( P=0.057 for interaction ) . CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events , nonfatal myocardial infa rct ion , or nonfatal stroke , as compared with simvastatin alone . These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . 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 
    Output:
    
Conclusions Our study indicated that fibrate therapy might play an important role in reducing the risk of fatal stroke in patients with previous diabetes , cardiovascular disease or stroke .
However , it did not have an effect on the incidence of stroke