OMEGA, a Randomized, Placebo-Controlled Trial to Test the Effect of Highly Purified Omega-3 Fatty Acids on Top of Modern Guideline-Adjusted Therapy After Myocardial Infarction Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: Results of GISSI-prevenzione trial Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia. Randomized, Double-Blind, Placebo-Controlled Trial of Fish Oil and Mustard Oil in Patients with Suspected Acute Myocardial Infarction: The Indian Experiment of Infarct Survival—4 EFFECTS OF CHANGES IN FAT, FISH, AND FIBRE INTAKES ON DEATH AND MYOCARDIAL REINFARCTION: DIET AND REINFARCTION TRIAL (DART) Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial n-3 fatty acids and cardiovascular events after myocardial infarction. Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction (from The Heart Institute of Spokane Diet Intervention and Evaluation Trial). Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial
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 [ RR ] , 0.93 ; 99 % CI , 0.83 - 1.03 ; P = .05 ) , nonfatal myocardial infa rct ion ( RR , 0.97 ; 99 % CI , 0.87 - 1.08 ; P = .43 ) or any coronary heart disease events ( RR , 0.96 ; 95 % CI , 0.90 - 1.01 ; P = .12 ) . Neither did r and omization to omega-3 fatty acid supplementation have any significant associations with major vascular events ( RR , 0.97 ; 95 % CI , 0.93 - 1.01 ; P = .10 ) , overall or in any subgroups , including subgroups composed of persons with prior coronary heart disease , diabetes , lipid levels greater than a given cutoff level , or statin use . Conclusions and Relevance This meta- analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events . It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results Objective To investigate whether dietary supplementation with B vitamins or omega 3 fatty acids , or both , could prevent major cardiovascular events in patients with a history of ischaemic heart disease or stroke . Design Double blind , r and omised , placebo controlled trial ; factorial design . Setting Recruitment throughout France via a network of 417 cardiologists , neurologists , and other physicians . Participants 2501 patients with a history of myocardial infa rct ion , unstable angina , or ischaemic stroke . Intervention Daily dietary supplement containing 5-methyltetrahydrofolate ( 560 μg ) , vitamin B-6 ( 3 mg ) , and vitamin B-12 ( 20 μg ) or placebo ; and containing omega 3 fatty acids ( 600 mg of eicosapentanoic acid and docosahexaenoic acid at a ratio of 2:1 ) or placebo . Median duration of supplementation was 4.7 years . Main outcome measures Major cardiovascular events , defined as a composite of non-fatal myocardial infa rct ion , stroke , or death from cardiovascular disease . Results Allocation to B vitamins lowered plasma homocysteine concentrations by 19 % compared with placebo , but had no significant effects on major vascular events ( 75 v 82 patients , hazard ratio , 0.90 ( 95 % confidence interval 0.66 to 1.23 , P=0.50 ) ) . Allocation to omega 3 fatty acids  increased plasma concentrations of omega 3 fatty acids by 37 % compared with placebo , but also had no significant effect on major vascular events ( 81 v 76 patients , hazard ratio 1.08 ( 0.79 to 1.47 , P=0.64 ) ) . Conclusion This study does not support the routine use of dietary supplements containing B vitamins or omega 3 fatty acids for prevention of cardiovascular disease in people with a history of ischaemic heart disease or ischaemic stroke , at least when supplementation is introduced after the acute phase of the initial event . Trial registration Current Controlled Trials IS RCT N41926726 OBJECTIVE To examine n-3 polyunsaturated fatty acid ( PUFA ) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability . METHODS AND RESULTS Patients awaiting carotid endarterectomy ( n=121 ) were r and omised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery ( median 21 days ) . The fatty acid compositions of plasma and carotid plaque phospholipids , plaque features , and expression of inflammatory genes were determined . The proportion of eicosapentaenoic acid ( EPA ) was higher ( P<0.0001 ) in carotid plaque phospholipids in patients in the n-3 PUFA group . Plaques from patients in the n-3 PUFA group had fewer foam cells ( P=0.0390 ) . There were no other differences between plaques in the two groups with regard to histological characteristics or morphology . Plaque stability was not different between the two groups . However , the EPA content of plaque phospholipids was inversely associated with plaque instability ( P=0.0209 ) , plaque inflammation ( P=0.0108 ) , the number of T cells in the plaque ( P=0.0097 ) and a summary score considering a range of plaque features ( P=0.0425 ) . Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 ( P=0.0055 ) , -9 ( P=0.0048 ) and -12 ( P=0.0044 ) and for interleukin-6 ( P=0.0395 ) and intercellular adhesion molecule 1 ( P=0.0142 ) . CONCLUSIONS Atherosclerotic plaques readily incorporate EPA . A higher plaque EPA content is associated with a reduced number of foam cells and T cells , less inflammation and increased stability A remarkable reduction of plasma concentrations of high-density lipoproteins ( HDL ) , especially of the HDL(2 ) subfraction , is one of the typical lipoprotein alterations found in patients with familial combined hyperlipidemia ( FCHL ) . Fourteen FCHL patients received 4 capsules daily of Omacor ( an omega-3 polyunsaturated fatty acid [ omega3 FA ] concentrate providing 1.88 g of eicosapentaenoic acid [ EPA ] and 1.48 g of docosahexaenoic acid [ DHA ] per day ; Pronova Biocare , Oslo , Norway ) or placebo for 8 weeks in a r and omized , double-blind , crossover study . Plasma triglycerides were 44 % lower , and LDL cholesterol and apoliporpotein (apo)B were 25 % and 7 % higher after Omacor than placebo . HDL cholesterol was higher ( + 8 % ) after Omacor than placebo , but this difference did not achieve statistical significance . Omacor caused a selective increase of the more buoyant HDL(2 ) subfraction ; plasma HDL(2 ) cholesterol and total mass increased by 40 % and 26 % , respectively , whereas HDL(3 ) cholesterol and total mass decreased by 4 % and 6 % . Both HDL(2 ) and HDL(3 ) were enriched in cholesteryl esters and depleted of triglycerides after Omacor . No changes were observed in the plasma concentration of major HDL apolipoproteins , LpA-I and LpA-I : A-II particles , lecithin : cholesterol acyltransferase ( LCAT ) , and cholesteryl ester transfer protein ( CETP ) . The plasma concentration of the HDL-bound antioxidant enzyme paraoxonase increased by 10 % after Omacor . Omacor may be helpful in correcting multiple lipoprotein abnormalities and reducing cardiovascular risk in FCHL patients In a r and omized , placebo-controlled trial , the effects of treatment with fish oil ( eicosapentaenoic acid , 1.08 g/day ) and mustard oil ( alpha-linolenic acid , 2.9 g/day ) were compared for 1 year in the management of 122 patients ( fish oil , group A ) , 120 patients ( mustard oil , group B ) , and 118 patients ( placebo , group C ) with suspected acute myocardial infa rct ion ( AMI ) . Treatments were administered about ( mean ) 18 hours after the symptoms of AMI in all three groups . The extent of cardiac disease , rise in cardiac enzymes , and lipid peroxides were comparable among the groups at entry into the study . After 1 year total cardiac events were significantly less in the fish oil and mustard oil groups compared with the placebo group ( 24.5 % and 28 % vs. 34.7 % , p > 0.01 ) . Nonfatal infa rct ions were also significantly less in the fish oil and mustard oil groups compared with the placebo group ( 13.0 % and 15.0 % vs. 25.4 % , p > 0.05 ) . Total cardiac deaths showed no significant reduction in the mustard oil group ; however , the fish oil group had significantly less cardiac deaths compared with the placebo group ( 11.4 % vs. 22.0 % , p > 0.05 ) . Apart from the decrease in the cardiac event rate , the fish oil and mustard oil groups also showed a significant reduction in total cardiac arrhythmias , left ventricular enlargement , and angina pectoris compared with the placebo group . Reductions in blood lipoproteins in the two intervention groups were modest and do not appear to be the cause of the benefit in the two groups . Diene conjugates showed a significant reduction in the fish oil and mustard oil groups , indicating that a part of the benefit may be caused by the reduction in oxidative stress . The findings of this study suggest that fish oil and mustard oil , possibly due to the presence of n-3 fatty acids , may provide rapid protective effects in patients with AMI . However , a large study is necessary to confirm this suggestion A r and omised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infa rct ion ( MI ) . 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors : a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat , an increase in fatty fish intake , and an increase in cereal fibre intake . The advice on fat was not associated with any difference in mortality , perhaps because it produced only a small reduction ( 3 - 4 % ) in serum cholesterol . The subjects advised to eat fatty fish had a 29 % reduction in 2 year all-cause mortality compared with those not so advised . This effect , which was significant , was not altered by adjusting for ten potential confounding factors . Subjects given fibre advice had a slightly higher mortality than other subjects ( not significant ) . The 2 year incidence of reinfa rct ion plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens . A modest intake of fatty fish ( two or three portions per week ) may reduce mortality in men who have recovered from MI BACKGROUND N-3 polyunsaturated fatty acids ( PUFAs ) from oily fish protect against death from cardiovascular disease . We aim ed to assess the hypothesis that incorporation of n-3 and n-6 PUFAs into advanced atherosclerotic plaques increases and decreases plaque stability , respectively . METHODS We did a r and omised controlled trial of patients awaiting carotid endarterectomy . We r and omly allocated patients control , sunflower oil ( n-6 ) , or fish-oil ( n-3 ) capsules until surgery . Primary outcome was plaque morphology indicative of stability or instability , and outcome measures were concentrations of EPA , DHA , and linoleic acid in carotid plaques ; plaque morphology ; and presence of macrophages in plaques . Analysis was per protocol . FINDINGS 188 patients were enrolled and r and omised ; 18 withdrew and eight were excluded . Duration of oil treatment was 7 - 189 days ( median 42 ) and did not differ between groups . The proportions of EPA and DHA were higher in carotid plaque fractions in patients receiving fish oil compared with those receiving control ( absolute difference 0.5 [ 95 % CI 0.3 - 0.7 ] , 0.4 [ 0.1 - 0.6 ] , and 0.2 [ 0.1 - 0.4 ] g/100 g total fatty acids for EPA ; and 0.3 [ 0.0 - 0.8 ] , 0.4 [ 0.1 - 0.7 ] , and 0.3 [ 0.1 - 0.6 ] g/100 g total fatty acids for DHA ; in plaque phospholipids , cholesteryl esters , and triacylglycerols , respectively ) . Sunflower oil had little effect on the fatty acid composition of lipid fractions . Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation , compared with plaques in patients in the control and sunflower oil groups ( odds ratio 0.52 [ 95 % CI 0.24 - 0.89 ] and 1.19 [ 1.02 - 1.57 ] vs control ; 0.49 [ 0.23 - 0.90 ] and 1.16 [ 1.01 - 1.53 ] vs sunflower oil ) . The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups . Carotid plaque morphology and infiltration by macrophages did not differ between control and sunflower oil groups . INTERPRETATION Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation , inducing changes that can enhance stability of atherosclerotic plaques . By contrast , increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here . Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake BACKGROUND Results from prospect i ve cohort studies and r and omized , controlled trials have provided evidence of a protective effect of n-3 fatty acids against cardiovascular diseases . We examined the effect of the marine n-3 fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) and of the plant-derived alpha-linolenic acid ( ALA ) on the rate of cardiovascular events among patients who have had a myocardial infa rct ion . METHODS In a multicenter , double-blind , placebo-controlled trial , we r and omly assigned 4837 patients , 60 through 80 years of age ( 78 % men ) , who had had a myocardial infa rct ion and were receiving state-of-the-art antihypertensive , antithrombotic , and lipid-modifying therapy to receive for 40 months one of four trial margarines : a margarine supplemented with a combination of EPA and DHA ( with a targeted additional daily intake of 400 mg of EPA-DHA ) , a margarine supplemented with ALA ( with a targeted additional daily intake of 2 g of ALA ) , a margarine supplemented with EPA-DHA and ALA , or a placebo margarine . The primary end point was the rate of major cardiovascular events , which comprised fatal and nonfatal cardiovascular events and cardiac interventions . Data were analyzed according to the intention-to-treat principle , with the use of Cox proportional-hazards models . RESULTS The patients consumed , on average , 18.8 g of margarine per day , which result ed in additional intakes of 226 mg of EPA combined with 150 mg of DHA , 1.9 g of ALA , or both , in the active-treatment groups . During the follow-up period , a major cardiovascular event occurred in 671 patients ( 13.9 % ) . Neither EPA-DHA nor ALA reduced this primary end point ( hazard ratio with EPA-DHA , 1.01 ; 95 % confidence interval [ CI ] , 0.87 to 1.17 ; P=0.93 ; hazard ratio with ALA , 0.91 ; 95 % CI , 0.78 to 1.05 ; P=0.20 ) . In the prespecified subgroup of women , ALA , as compared with placebo and EPA-DHA alone , was associated with a reduction in the rate of major cardiovascular events that approached significance ( hazard ratio , 0.73 ; 95 % CI , 0.51 to 1.03 ; P=0.07 ) . The rate of adverse events did not differ significantly among the study groups . CONCLUSIONS Low-dose supplementation with EPA-DHA or ALA did not significantly reduce the rate of major cardiovascular events among patients who had had a myocardial infa rct ion and who were receiving state-of-the-art antihypertensive , antithrombotic , and lipid-modifying therapy . ( Funded by the Netherl and s Heart Foundation and others ; Clinical Trials.gov number , NCT00127452 . ) Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain . The objectives of this study were to actively compare low-fat and Mediterranean-style diets  after first myocardial infa rct ion ( MI ) in a r and omized , controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis . First MI survivors were r and omized to a  low-fat ( n = 50 ) or Mediterranean-style ( n = 51 ) diet . The 2 diets were low in saturated fat ( < or = 7 % kcal ) and cholesterol ( < or = 200 mg/day ) ; the Mediterranean-style diet was distinguished by greater omega-3 fat intake ( > 0.75 % kcal ) . Participants received individual dietary counseling sessions , 2 within the first month and again at 3 , 6 , 12 , 18 , and 24 months , along with 6 group sessions . Combined dietary intervention  groups ( cases , n = 101 ) were compared with a usual-care group ( controls , n = 101 ) matched for age , gender , MI type and treatment , and status of diabetes mellitus and hypertension . Primary - outcome -free survival ( a composite of all-cause and cardiac deaths , MI , hospital admissions for heart failure , unstable angina pectoris , or stroke ) did not differ between low-fat ( 42 of 50 ) and Mediterranean-style ( 43 of 51 ) diet groups over a median follow-up period of 46 months ( range 18 to 72 ; log-rank p = 0.81 ) . Patients receiving dietary intervention had better primary - outcome -free survival ( 85 of 101 ) than usual-care controls ( 61 of 101 ) ( log-rank p < 0.001 ) , with unadjusted and adjusted odds ratios of 0.33 ( 95 % confidence interval 0.18 to 0.60 , p < 0.001 ) and 0.28 ( 95 % confidence interval 0.13 to 0.63 , p = 0.002 ) , respectively . In conclusion , active intervention with either a low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI Background : Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects , but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infa rct ion while receiving current guideline -based therapy remains unknown . Methods : In a multicenter , double-blind , placebo-controlled trial , participants presenting with an acute myocardial infa rct ion were r and omly assigned 1:1 to 6 months of high-dose omega-3 fatty acids ( n=180 ) or placebo ( n=178 ) . Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy . The primary study endpoint was change in left ventricular systolic volume index . Secondary endpoints included change in noninfa rct myocardial fibrosis , left ventricular ejection fraction , and infa rct size . Results : By intention-to-treat analysis , patients r and omly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index ( –5.8 % , P=0.017 ) , and noninfa rct myocardial fibrosis ( –5.6 % , P=0.026 ) in comparison with placebo . Per- protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13 % reduction in left ventricular systolic volume index in comparison with the lowest quartile . In addition , patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis . There were no adverse events associated with high-dose omega-3 fatty acid therapy . Conclusions : Treatment of patients with acute myocardial infa rct ion with high-dose  omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling , noninfa rct myocardial fibrosis , and serum biomarkers of systemic inflammation beyond current guideline -based st and ard of care . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT00729430
Background The purpose of this review is to examine the effect of Omega-3 Fatty acids on mortality , morbidity , and adverse events in patients with acute myocardial infa rct ion ( AMI ) .