title: Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis.
abstract: BACKGROUND
  Considerable controversy exists regarding the association of omega-3 polyunsaturated fatty acids (PUFAs) and major cardiovascular end points.
  
  
  OBJECTIVE
  To assess the role of omega-3 supplementation on major cardiovascular outcomes.
  
  
  METHODS
  MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012.
  
  
  METHODS
  Randomized clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke.
  
  
  METHODS
  Descriptive and quantitative information was extracted; absolute and relative risk (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I2. Subgroup analyses were performed for the presence of blinding, the prevention settings, and patients with implantable cardioverter-defibrillators, and meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of .0063 was assumed after adjustment for multiple comparisons.
  
  
  RESULTS
  Of the 3635 citations retrieved, 20 studies of 68,680 patients were included, reporting 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No statistically significant association was observed with all-cause mortality (RR, 0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] -0.004, 95% CI, -0.01 to 0.02), cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, -0.01; 95% CI, -0.02 to 0.00), sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, -0.003; 95% CI, -0.012 to 0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, -0.002; 95% CI, -0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95% CI, -0.002 to 0.004) when all supplement studies were considered.
  
  
  CONCLUSIONS
  Overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.
authors.affiliation: Lipid Disorders Clinic, Department of Internal Medicine, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Evangelos C
authors.initials: EC
authors.lastname: Rizos
authors.forename: Evangelia E
authors.initials: EE
authors.lastname: Ntzani
authors.forename: Eftychia
authors.initials: E
authors.lastname: Bika
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kostapanos
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000517:prevention & control*; D002423:Cause of Death; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000401:mortality / Q000517:prevention & control
chemical_list: D015525:Fatty Acids, Omega-3