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: Background — There is no r and omized , double-blind trial testing the prognostic effect of highly purified omega-3 fatty acids in addition to current guideline -adjusted treatment of acute myocardial infa rct ion . Methods and Results — OMEGA is a r and omized , placebo-controlled , double-blind , multicenter trial testing the effects of omega-3-acid ethyl esters-90 ( 1 g/d for 1 year ) on the rate of sudden cardiac death in survivors of acute myocardial infa rct ion , if given in addition to current guideline -adjusted treatment . Secondary end points were total mortality and nonfatal clinical events .  Patients ( n=3851 ; female , 25.6 % ; mean age , 64.0 years ) were r and omized in 104 German centers 3 to 14 days after acute myocardial infa rct ion from October 2003 until June 2007 .  Acute coronary angiography was performed in 93.8 % and acute percutaneous coronary intervention in 77.8 % of all patients . During a follow-up of 365 days , the event rates were ( omega and control groups ) as follows : sudden cardiac death , 1.5 % and 1.5 % ( P=0.84 ) ; total mortality , 4.6 % and 3.7 % ( P=0.18 ) ; major adverse cerebrovascular and cardiovascular events , 10.4 % and 8.8 % ( P=0.1 ) ; and revascularization in survivors , 27.6 % and 29.1 % ( P=0.34 ) . Conclusions — Guideline -adjusted treatment of acute myocardial infa rct ion results in a low rate of sudden cardiac death and other clinical events within 1 year of follow-up , which could not be shown to be further reduced by the application of omega-3 fatty acids . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00251134 BACKGROUND The Lyon Diet Heart Study is a r and omized secondary prevention trial aim ed at testing whether a Mediterranean-type diet may reduce the rate of recurrence  after a first myocardial infa rct ion . An intermediate analysis showed a striking protective effect after 27 months of follow-up . This report presents results of an extended follow-up ( with a mean of 46 months per patient ) and deals with the relationships of dietary patterns and traditional risk factors with recurrence . METHODS AND RESULTS Three composite outcomes ( COs ) combining either cardiac death and nonfatal myocardial infa rct ion ( CO 1 ) , or the preceding plus major secondary end points ( unstable angina , stroke , heart failure , pulmonary or peripheral embolism ) ( CO 2 ) , or the preceding plus minor events requiring hospital admission ( CO 3 ) were studied . In the  Mediterranean diet group , CO 1 was reduced ( 14 events versus 44 in the prudent Western-type diet group , P=0.0001 ) , as were CO 2 ( 27 events versus 90 , P=0.0001 ) and CO 3 ( 95 events versus 180 , P=0 . 0002 ) . Adjusted risk ratios ranged from 0.28 to 0.53 . Among the traditional risk factors , total cholesterol ( 1 mmol/L being associated with an increased risk of 18 % to 28 % ) , systolic blood pressure ( 1 mm Hg being associated with an increased risk of 1 % to 2 % ) , leukocyte count ( adjusted risk ratios ranging from 1.64 to 2.86 with count > 9x10(9)/L ) , female sex ( adjusted risk ratios , 0.27 to 0 . 46 ) , and aspirin use ( adjusted risk ratios , 0.59 to 0.82 ) were each significantly and independently associated with recurrence . CONCLUSIONS The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infa rct ion , confirming previous intermediate analyses . Major traditional risk factors , such as high blood cholesterol and blood pressure , were shown to be independent and joint predictors of recurrence , indicating that the Mediterranean dietary pattern did not alter , at least qualitatively , the usual relationships between major risk factors and recurrence . Thus , a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet . It should be associated with other ( pharmacological ? ) means aim ed at reducing modifiable risk factors . Further trials combining the 2 approaches are warranted BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione was conceived as a population , pragmatic trial on patients with recent myocardial infa rct ions conducted in the framework of the Italian public health system . In GISSI-Prevenzione , patients were invited to follow Mediterranean dietary habits , and were treated with up-to- date preventive pharmacological interventions . Long-term n-3 PUFA ( 1 g daily ) but not vitamin E ( 300 mg daily ) , was beneficial for death and for combined death , nonfatal myocardial infa rct ion , and stroke . All the benefit , however , was attributable to the decrease in risk for overall , cardiovascular , cardiac , coronary , and sudden death . At variance with the orientation of a scientific scenario largely dominated by the “ cholesterol-heart hypothesis ” , GISSI-Prevenzione results indicate n-3 PUFA ( virtually devoid of any cholesterol-lowering effect ) as a relevant pharmacological treatment for secondary prevention after myocardial infa rct ion . As to the relevance and comparability of GISSI-Prevenzione results , up to 5.7 lives could be saved every 1000 patients with previous myocardial infa rct ion treated with n-3 PUFA ( 1 g daily ) per year . Such a result is comparable to that observed in the Long-Term Intervention with Pravastatin in Ischaemic Disease ( LIPID ) trial , where 5.2 lives could be saved per 1000 hypercholesterolemic , coronary heart disease patients treated with pravastatin for 1 yr . The choice of a relatively low-dose regimen ( 1-g capsule daily ) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits  , and the pattern of effects seen in GISSI-Prevenzione ( namely , reduction of overall mortality with no decrease in the rate of nonfatal myocardial infa rct ion ) all strongly suggest that n-3 PUFA treatment should be considered a recommended new component of secondary prevention . The importance of this combined/additive effect is further suggested by the analyses of the interplay between diet and n-3 PUFA : There is an interesting direct correlation between size of the effect and “ correctness ” of background diets . It can be anticipated that a conceptual barrier must be overcome : A “ dietary drug ” should be added to “ dietary advice ” , which remains fundamental to allow this statement to become true in clinical practice BACKGROUND Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis . OBJECTIVE The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infa rct ion ( MI ) on subsequent cardiac events and serum lipids . DESIGN Three hundred patients with acute MI were r and omly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil , administered in a double-blind manner over 12 - 24 mo . Median follow-up time was 1.5 y. Clinical follow-up , including the drawing of blood sample s , was performed after 6 wk of treatment and later at 0.5-year intervals . RESULTS Forty-two ( 28 % ) patients in the n-3 group and 36 ( 24 % ) in the corn oil group experienced at least one cardiac event ( cardiac death , resuscitation , recurrent MI , or unstable angina ) . No significant difference in prognosis was observed between groups for single or combined cardiac events . Total cholesterol concentrations decreased in both groups , with no significant intergroup differences . On average , the monthly increase in HDL cholesterol was 1.11 % in the n-3 group and 0.55 % in the corn oil group ( P = 0.0016 ) . Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group , whereas they increased by 0.35%/mo in the corn oil group ( P < 0.0001 ) . CONCLUSION No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids Importance Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events  in people with prior coronary heart disease , but large trials of omega-3 fatty acids have produced conflicting results . Objective To conduct a meta- analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of  fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups . Data Sources and Study Selection This meta- analysis included r and omized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events . Data Extraction and Synthesis Aggregated study -level data were obtained from 10 large r and omized clinical trials . Rate ratios for each trial were synthesized using observed minus expected statistics and variances . Summary rate ratios were estimated by a fixed-effects meta- analysis using 95 % confidence intervals for major diseases and 99 % confidence intervals for all subgroups . Main Outcomes and Measures The main outcomes included fatal coronary heart disease , nonfatal myocardial infa rct ion , stroke , major vascular events , and all-cause mortality , as well as major vascular events in study population subgroups . Results Of the 77 917 high-risk individuals participating in the 10 trials , 47 803 ( 61.4 % ) were men , and the mean age at entry was 64.0 years ; the trials lasted a mean of 4.4 years . The associations of treatment with outcomes were assessed on 6273 coronary heart disease events ( 2695 coronary heart disease deaths and 2276 nonfatal myocardial infa rct ions ) and 12 001 major vascular events . R and omization to omega-3 fatty acid supplementation ( eicosapentaenoic acid dose range , 226 - 1800 mg/d ) had no significant associations with coronary heart disease death ( rate ratio [ R 
    Output:
    
agent
***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 — There is no r and omized , double-blind trial testing the prognostic effect of highly purified omega-3 fatty acids in addition to current guideline -adjusted treatment of acute myocardial infa rct ion . Methods and Results — OMEGA is a r and omized , placebo-controlled , double-blind , multicenter trial testing the effects of omega-3-acid ethyl esters-90 ( 1 g/d for 1 year ) on the rate of sudden cardiac death in survivors of acute myocardial infa rct ion , if given in addition to current guideline -adjusted treatment . Secondary end points were total mortality and nonfatal clinical events .  Patients ( n=3851 ; female , 25.6 % ; mean age , 64.0 years ) were r and omized in 104 German centers 3 to 14 days after acute myocardial infa rct ion from October 2003 until June 2007 .  Acute coronary angiography was performed in 93.8 % and acute percutaneous coronary intervention in 77.8 % of all patients . During a follow-up of 365 days , the event rates were ( omega and control groups ) as follows : sudden cardiac death , 1.5 % and 1.5 % ( P=0.84 ) ; total mortality , 4.6 % and 3.7 % ( P=0.18 ) ; major adverse cerebrovascular and cardiovascular events , 10.4 % and 8.8 % ( P=0.1 ) ; and revascularization in survivors , 27.6 % and 29.1 % ( P=0.34 ) . Conclusions — Guideline -adjusted treatment of acute myocardial infa rct ion results in a low rate of sudden cardiac death and other clinical events within 1 year of follow-up , which could not be shown to be further reduced by the application of omega-3 fatty acids . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00251134 BACKGROUND The Lyon Diet Heart Study is a r and omized secondary prevention trial aim ed at testing whether a Mediterranean-type diet may reduce the rate of recurrence  after a first myocardial infa rct ion . An intermediate analysis showed a striking protective effect after 27 months of follow-up . This report presents results of an extended follow-up ( with a mean of 46 months per patient ) and deals with the relationships of dietary patterns and traditional risk factors with recurrence . METHODS AND RESULTS Three composite outcomes ( COs ) combining either cardiac death and nonfatal myocardial infa rct ion ( CO 1 ) , or the preceding plus major secondary end points ( unstable angina , stroke , heart failure , pulmonary or peripheral embolism ) ( CO 2 ) , or the preceding plus minor events requiring hospital admission ( CO 3 ) were studied . In the  Mediterranean diet group , CO 1 was reduced ( 14 events versus 44 in the prudent Western-type diet group , P=0.0001 ) , as were CO 2 ( 27 events versus 90 , P=0.0001 ) and CO 3 ( 95 events versus 180 , P=0 . 0002 ) . Adjusted risk ratios ranged from 0.28 to 0.53 . Among the traditional risk factors , total cholesterol ( 1 mmol/L being associated with an increased risk of 18 % to 28 % ) , systolic blood pressure ( 1 mm Hg being associated with an increased risk of 1 % to 2 % ) , leukocyte count ( adjusted risk ratios ranging from 1.64 to 2.86 with count > 9x10(9)/L ) , female sex ( adjusted risk ratios , 0.27 to 0 . 46 ) , and aspirin use ( adjusted risk ratios , 0.59 to 0.82 ) were each significantly and independently associated with recurrence . CONCLUSIONS The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infa rct ion , confirming previous intermediate analyses . Major traditional risk factors , such as high blood cholesterol and blood pressure , were shown to be independent and joint predictors of recurrence , indicating that the Mediterranean dietary pattern did not alter , at least qualitatively , the usual relationships between major risk factors and recurrence . Thus , a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet . It should be associated with other ( pharmacological ? ) means aim ed at reducing modifiable risk factors . Further trials combining the 2 approaches are warranted BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione was conceived as a population , pragmatic trial on patients with recent myocardial infa rct ions conducted in the framework of the Italian public health system . In GISSI-Prevenzione , patients were invited to follow Mediterranean dietary habits , and were treated with up-to- date preventive pharmacological interventions . Long-term n-3 PUFA ( 1 g daily ) but not vitamin E ( 300 mg daily ) , was beneficial for death and for combined death , nonfatal myocardial infa rct ion , and stroke . All the benefit , however , was attributable to the decrease in risk for overall , cardiovascular , cardiac , coronary , and sudden death . At variance with the orientation of a scientific scenario largely dominated by the “ cholesterol-heart hypothesis ” , GISSI-Prevenzione results indicate n-3 PUFA ( virtually devoid of any cholesterol-lowering effect ) as a relevant pharmacological treatment for secondary prevention after myocardial infa rct ion . As to the relevance and comparability of GISSI-Prevenzione results , up to 5.7 lives could be saved every 1000 patients with previous myocardial infa rct ion treated with n-3 PUFA ( 1 g daily ) per year . Such a result is comparable to that observed in the Long-Term Intervention with Pravastatin in Ischaemic Disease ( LIPID ) trial , where 5.2 lives could be saved per 1000 hypercholesterolemic , coronary heart disease patients treated with pravastatin for 1 yr . The choice of a relatively low-dose regimen ( 1-g capsule daily ) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits  , and the pattern of effects seen in GISSI-Prevenzione ( namely , reduction of overall mortality with no decrease in the rate of nonfatal myocardial infa rct ion ) all strongly suggest that n-3 PUFA treatment should be considered a recommended new component of secondary prevention . The importance of this combined/additive effect is further suggested by the analyses of the interplay between diet and n-3 PUFA : There is an interesting direct correlation between size of the effect and “ correctness ” of background diets . It can be anticipated that a conceptual barrier must be overcome : A “ dietary drug ” should be added to “ dietary advice ” , which remains fundamental to allow this statement to become true in clinical practice BACKGROUND Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis . OBJECTIVE The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infa rct ion ( MI ) on subsequent cardiac events and serum lipids . DESIGN Three hundred patients with acute MI were r and omly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil , administered in a double-blind manner over 12 - 24 mo . Median follow-up time was 1.5 y. Clinical follow-up , including the drawing of blood sample s , was performed after 6 wk of treatment and later at 0.5-year intervals . RESULTS Forty-two ( 28 % ) patients in the n-3 group and 36 ( 24 % ) in the corn oil group experienced at least one cardiac event ( cardiac death , resuscitation , recurrent MI , or unstable angina ) . No significant difference in prognosis was observed between groups for single or combined cardiac events . Total cholesterol concentrations decreased in both groups , with no significant intergroup differences . On average , the monthly increase in HDL cholesterol was 1.11 % in the n-3 group and 0.55 % in the corn oil group ( P = 0.0016 ) . Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group , whereas they increased by 0.35%/mo in the corn oil group ( P < 0.0001 ) . CONCLUSION No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids Importance Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events  in people with prior coronary heart disease , but large trials of omega-3 fatty acids have produced conflicting results . Objective To conduct a meta- analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of  fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups . Data Sources and Study Selection This meta- analysis included r and omized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events . Data Extraction and Synthesis Aggregated study -level data were obtained from 10 large r and omized clinical trials . Rate ratios for each trial were synthesized using observed minus expected statistics and variances . Summary rate ratios were estimated by a fixed-effects meta- analysis using 95 % confidence intervals for major diseases and 99 % confidence intervals for all subgroups . Main Outcomes and Measures The main outcomes included fatal coronary heart disease , nonfatal myocardial infa rct ion , stroke , major vascular events , and all-cause mortality , as well as major vascular events in study population subgroups . Results Of the 77 917 high-risk individuals participating in the 10 trials , 47 803 ( 61.4 % ) were men , and the mean age at entry was 64.0 years ; the trials lasted a mean of 4.4 years . The associations of treatment with outcomes were assessed on 6273 coronary heart disease events ( 2695 coronary heart disease deaths and 2276 nonfatal myocardial infa rct ions ) and 12 001 major vascular events . R and omization to omega-3 fatty acid supplementation ( eicosapentaenoic acid dose range , 226 - 1800 mg/d ) had no significant associations with coronary heart disease death ( rate ratio [ R 
    Output:
    