human
***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: Objective —To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol , The Evaluation of Choline Fenofibrate ( ABT-335 ) on Carotid Intima-Media Thickness ( cIMT ) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy ( FIRST ) trial evaluated the effects of fenofibric acid ( FA ) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin . Approach and Results —This multicenter , double-blind , placebo-controlled study was performed in patients with mixed dyslipidemia ( fasting triglycerides , ≥150 mg/dL ; high-density lipoprotein cholesterol , ⩽45 [ men ] or 55 mg/dL [ women ] ; low-density lipoprotein cholesterol , ⩽100 mg/dL once and averaging ⩽105 mg/dL ) and a history of coronary heart disease or risk equivalent . Patients on background atorvastatin ( continued on starting dose or titrated to 40 mg , if needed ) were r and omized to FA 135 mg or placebo . The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT , measured by ultrasound . In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy , rate of change in posterior-wall cIMT was similar with FA plus atorvastatin ( −0.006 mm/y ) versus atorvastatin monotherapy ( 0.000 mm/y ; P=0.22 ) . FA plus atorvastatin was favored ( P<0.05 ) in 5 of 24 prespecified subgroups : age ≥60 years , history of coronary artery disease , cIMT > 0.795 mm , triglycerides 170 to 235 mg/dL , and statin use at entry . Adverse events were consistent with the known safety profiles of both drugs ; however , FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy ( 6.5 % versus 0.9 % ) . Conclusions —Compared with atorvastatin monotherapy , FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia 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 BACKGROUND Although cardiovascular disease and low high-density lipoprotein ( HDL ) cholesterol are common in people with renal insufficiency , data addressing the cardiovascular benefits of fibric acid derivatives in this population are sparse . We conducted a post hoc subgroup analysis of a r and omized double-blind , placebo-controlled trial to determine whether gemfibrozil is effective and safe for secondary prevention of cardiovascular events in individuals with chronic renal insufficiency ( CRI ) . METHODS Using an analysis plan that was developed a priori , we analyzed data from the Veterans ' Affairs High-Density Lipoprotein Intervention Trial ( VA-HIT ) study ; a r and omized trial of gemfibrozil versus placebo in 2531 men with established coronary disease , an HDL cholesterol level of 40 mg/dL ( 1.0 mmol/L ) or less , and a low-density lipoprotein ( LDL ) cholesterol level of 140 mg/dL ( 3.6 mmol/L ) or less . Of these , 1046 men had CRI as defined by creatinine clearance < /=75 mL/min using the Cockcroft-Gault equation , 99.8 % of whom had either mild or moderate renal impairment ( creatinine clearance 60 - 75 or 30 - 59.9 mL/min , respectively ) . RESULTS The incidence of the primary outcome ( coronary death or nonfatal myocardial infa rct ion ) was lower in participants with CRI who received gemfibrozil compared to placebo [ hazard ratio ( HR ) 0.73 ; 95 % CI 0.56 - 0.96 , P= 0.02 ) . The cumulative incidence of the primary end point was reduced from 24.3 % to 18.2 % . In subjects with CRI , gemfibrozil also significantly reduced the risk of the combined outcome of coronary death , nonfatal myocardial infa rct ion , or stroke ( HR 0.74 , 95 % CI 0.58 - 0.95 , P= 0.02 ) , but not the need for coronary revascularization ( HR 0.85 , 95 % CI 0.66 - 1.10 , P= 0.21 ) or total mortality ( HR 1.03 , 95 % CI 0.78 - 1.35 , P= 0.85 ) . The overall incidence of adverse effects was similar in individuals receiving gemfibrozil and placebo . However , the risk of sustained increases in serum creatinine was increased in gemfibrozil recipients compared with placebo ( 5.9 vs. 2.8 % , P= 0.02 ) . CONCLUSION Gemfibrozil appears effective for secondary prevention of cardiovascular events in individuals with mild to moderate chronic renal insufficiency and HDL cholesterol of 40 mg/dL or less . However , the benefit and safety of gemfibrozil in people with more severe impairment of kidney function requires further study 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 OBJECTIVE To determine whether serum lipid intervention , in addition to conventional diabetes treatment , could alter cardiovascular outcomes in type 2 diabetes . RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects ( 117 men , 47 women ) without a history of clinical cardiovascular disease r and omized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospect ively for a minimum of 3 years . Serial biochemical and noninvasive vascular assessment s , carotid and femoral artery B-mode ultrasound measurements , and those pertaining to coronary heart disease (CHD)— clinical history , the World Health Organization ( WHO ) cardiovascular question naire , and resting and exercise electrocardiogram (ECG)—were recorded . RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride ( −32 vs. 4 % , P = 0.001 ) , total cholesterol ( −7 vs. −0.3 % , P = 0.004 ) , and total−to-HDL cholesterol ratio ( −12 vs. −0.0 % , P = 0.001 ) , and an 
    Output:
    
agent
Subgroup analyses showed the benefit of fibrates on the primary composite outcome to be consistent irrespective of age , gender , and diabetes mellitus .
Moderate evidence showed that the fibrate class can be effective in the secondary prevention of composite outcome of non-fatal stroke , non-fatal MI , and vascular death .
However , this beneficial effect relies on the inclusion of clofibrate data , a drug that was discontinued in 2002 due to its unacceptably large adverse effects .
***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: Objective —To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol , The Evaluation of Choline Fenofibrate ( ABT-335 ) on Carotid Intima-Media Thickness ( cIMT ) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy ( FIRST ) trial evaluated the effects of fenofibric acid ( FA ) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin . Approach and Results —This multicenter , double-blind , placebo-controlled study was performed in patients with mixed dyslipidemia ( fasting triglycerides , ≥150 mg/dL ; high-density lipoprotein cholesterol , ⩽45 [ men ] or 55 mg/dL [ women ] ; low-density lipoprotein cholesterol , ⩽100 mg/dL once and averaging ⩽105 mg/dL ) and a history of coronary heart disease or risk equivalent . Patients on background atorvastatin ( continued on starting dose or titrated to 40 mg , if needed ) were r and omized to FA 135 mg or placebo . The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT , measured by ultrasound . In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy , rate of change in posterior-wall cIMT was similar with FA plus atorvastatin ( −0.006 mm/y ) versus atorvastatin monotherapy ( 0.000 mm/y ; P=0.22 ) . FA plus atorvastatin was favored ( P<0.05 ) in 5 of 24 prespecified subgroups : age ≥60 years , history of coronary artery disease , cIMT > 0.795 mm , triglycerides 170 to 235 mg/dL , and statin use at entry . Adverse events were consistent with the known safety profiles of both drugs ; however , FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy ( 6.5 % versus 0.9 % ) . Conclusions —Compared with atorvastatin monotherapy , FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia 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 BACKGROUND Although cardiovascular disease and low high-density lipoprotein ( HDL ) cholesterol are common in people with renal insufficiency , data addressing the cardiovascular benefits of fibric acid derivatives in this population are sparse . We conducted a post hoc subgroup analysis of a r and omized double-blind , placebo-controlled trial to determine whether gemfibrozil is effective and safe for secondary prevention of cardiovascular events in individuals with chronic renal insufficiency ( CRI ) . METHODS Using an analysis plan that was developed a priori , we analyzed data from the Veterans ' Affairs High-Density Lipoprotein Intervention Trial ( VA-HIT ) study ; a r and omized trial of gemfibrozil versus placebo in 2531 men with established coronary disease , an HDL cholesterol level of 40 mg/dL ( 1.0 mmol/L ) or less , and a low-density lipoprotein ( LDL ) cholesterol level of 140 mg/dL ( 3.6 mmol/L ) or less . Of these , 1046 men had CRI as defined by creatinine clearance < /=75 mL/min using the Cockcroft-Gault equation , 99.8 % of whom had either mild or moderate renal impairment ( creatinine clearance 60 - 75 or 30 - 59.9 mL/min , respectively ) . RESULTS The incidence of the primary outcome ( coronary death or nonfatal myocardial infa rct ion ) was lower in participants with CRI who received gemfibrozil compared to placebo [ hazard ratio ( HR ) 0.73 ; 95 % CI 0.56 - 0.96 , P= 0.02 ) . The cumulative incidence of the primary end point was reduced from 24.3 % to 18.2 % . In subjects with CRI , gemfibrozil also significantly reduced the risk of the combined outcome of coronary death , nonfatal myocardial infa rct ion , or stroke ( HR 0.74 , 95 % CI 0.58 - 0.95 , P= 0.02 ) , but not the need for coronary revascularization ( HR 0.85 , 95 % CI 0.66 - 1.10 , P= 0.21 ) or total mortality ( HR 1.03 , 95 % CI 0.78 - 1.35 , P= 0.85 ) . The overall incidence of adverse effects was similar in individuals receiving gemfibrozil and placebo . However , the risk of sustained increases in serum creatinine was increased in gemfibrozil recipients compared with placebo ( 5.9 vs. 2.8 % , P= 0.02 ) . CONCLUSION Gemfibrozil appears effective for secondary prevention of cardiovascular events in individuals with mild to moderate chronic renal insufficiency and HDL cholesterol of 40 mg/dL or less . However , the benefit and safety of gemfibrozil in people with more severe impairment of kidney function requires further study 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 OBJECTIVE To determine whether serum lipid intervention , in addition to conventional diabetes treatment , could alter cardiovascular outcomes in type 2 diabetes . RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects ( 117 men , 47 women ) without a history of clinical cardiovascular disease r and omized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospect ively for a minimum of 3 years . Serial biochemical and noninvasive vascular assessment s , carotid and femoral artery B-mode ultrasound measurements , and those pertaining to coronary heart disease (CHD)— clinical history , the World Health Organization ( WHO ) cardiovascular question naire , and resting and exercise electrocardiogram (ECG)—were recorded . RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride ( −32 vs. 4 % , P = 0.001 ) , total cholesterol ( −7 vs. −0.3 % , P = 0.004 ) , and total−to-HDL cholesterol ratio ( −12 vs. −0.0 % , P = 0.001 ) , and an 
    Output:
    