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Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta-analysis

Evangelos C. Rizos, MD, PhD; Evangelia E. Ntzani, MD, PhD; Eftychia Bika, MD; Michael S. Kostapanos, MD; Moses S. Elisaf, MD, PhD, FASA, FRSH
JAMA. 2012;308(10):1024-1033. doi:10.1001/2012.jama.11374.
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Published online

Context 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.

Data Sources MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012.

Study Selection Randomized clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke.

Data Extraction 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.

Data Synthesis 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.

Conclusion 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.

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Figures

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Figure 1. Flowchart for the Selection of Eligible Studies
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Figure 2. Efficacy of Omega-3 Polyunsaturated Fatty Acids Administration Through Dietary Counseling
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Error bars indicate 95% CIs; MI, myocardial infarction; PUFAs, polyunsaturated fatty acids; RR, relative risk.

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Figure 3. Efficacy of Omega-3 Polyunsaturated Fatty Acid Supplements Across Different Outcomes
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Error bars indicate 95% CIs; PUFAs, polyunsaturated fatty acids; RR, relative risk.

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Figure 4. Meta-analysis of Omega-3 Supplements for All-Cause Mortality
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Error bars indicate 95% CIs of the relative risk (RR) estimates. The size of the squares correspond to the study weight in the random-effects meta-analysis. Diamonds represent the meta-analysis summary effect estimate. ICD indicates implantable cardioverter-defibrillator; PUFAs, polyunsaturated fatty acids.

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Figure 5. Cumulative Meta-analysis of the Omega-3 Supplements for All-Cause Mortality
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Error bars indicate the 95% CI of the cumulative meta-analysis estimates as randomized patients accumulate through time. PUFAs indicates polyunsaturated fatty acids; RR, relative risk.

Tables

References

January 2, 2013
Evan J. H. Lewis, MSc
JAMA. 2013;309(1):27. doi:10.1001/jama.2012.116654.
January 2, 2013
Ankur Sethi, MD; Mukesh Singh, MD; Rohit Arora, MD
JAMA. 2013;309(1):27. doi:10.1001/jama.2012.116644.
January 2, 2013
Charalambos Vlachopoulos, MD; Dimitrios Richter, MD; Christodoulos Stefanadis, MD, PhD
JAMA. 2013;309(1):27. doi:10.1001/jama.2012.116651.
January 2, 2013
Claudio Galli, MD, PhD; J. Thomas Brenna, PhD
JAMA. 2013;309(1):27. doi:10.1001/jama.2012.116648.
January 2, 2013
Evangelos C. Rizos, MD, PhD; Evangelia E. Ntzani, MD, PhD; Moses S. Elisaf, MD, PhD
JAMA. 2013;309(1):27. doi:10.1001/jama.2012.116657.
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