Review
N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials

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Abstract

Purpose

Observational studies have shown an inconsistent association between n-3 polyunsaturated fatty acids and the risk of coronary heart disease. We investigated the effects of dietary and nondietary (supplemental) intake of n-3 polyunsaturated fatty acids on coronary heart disease.

Subjects and methods

We searched the literature to identify randomized controlled trials that compared dietary or nondietary intake of n-3 polyunsaturated fatty acids with a control diet or placebo in patients with coronary heart disease. Studies had to have at least 6 months of follow-up data, and to have reported clinical endpoint data. We identified 11 trials, published between 1966 and 1999, which included 7951 patients in the intervention and 7855 patients in the control groups.

Results

The risk ratio of nonfatal myocardial infarction in patients who were on n-3 polyunsaturated fatty acid-enriched diets compared with control diets or placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.2, P = 0.16; Breslow-Day test for heterogeneity, P = 0.01), and the risk ratio of fatal myocardial infarction was 0.7 (95% CI: 0.6 to 0.8, P <0.001; heterogeneity P >0.20). In 5 trials, sudden death was associated with a risk ratio of 0.7 (95% CI: 0.6 to 0.9, P <0.01; heterogeneity P >0.20), whereas the risk ratio of overall mortality was 0.8 (95% CI: 0.7 to 0.9, P <0.001; heterogeneity P >0.20). There was no difference in summary estimates between dietary and nondietary interventions of n-3 polyunsaturated fatty acids for all endpoints.

Conclusion

This meta-analysis suggests that dietary and nondietary intake of n-3 polyunsaturated fatty acids reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease.

Section snippets

Methods

We searched MEDLINE, EMBASE, Pascal BioMed, and Index Medicus for all randomized controlled trials, published in all languages from 1966 through August 1999, which compared n-3 polyunsaturated fatty acids, given either as supplements or via dietary intervention, with placebo or a control diet. We combined the terms omega 3 fatty acids, fish oils, diet, dietary therapy, and cardiovascular disease with text searches using the terms random or control. We also searched the Cochrane Library and

Results

Our literature search identified 406 studies, and 369 additional articles were reviewed in the Cochrane Library. We identified 177 trials, and excluded 129 that were not related to coronary heart disease, 26 that had a follow-up of less than 6 months or did not report clinical endpoint data, and 7 that were duplicate publications. Four studies included patients who had undergone heart transplantation or bypass surgery, and were therefore also excluded.

Eleven trials fulfilled our inclusion

Discussion

Our meta-analysis suggests that a diet supplemented with n-3 polyunsaturated fatty acids may decrease mortality due to myocardial reinfarction, sudden death, and overall mortality in patients with coronary heart disease. The risk reduction for mortality was statistically significant. The mortality in control groups of trials that followed patients for an average of 1.5 years varied from 1% to 22%, suggesting that in low-risk patients (e.g., those aged <50 years and with minor uncomplicated

Acknowledgements

The authors would like to thank Peter Wolf, PhD, for conducting the literature search and Odd Johansen, MD, for providing additional data from his study.

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    Supported by a grant from the University of Basel Hospitals, Byk AG, Switzerland, and Semomed AG, Switzerland.

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