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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

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Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review

and .

Review published: .

CRD summary

This review concluded that dietary supplements of omega-3 fatty acids decreased cardiac death, all-cause mortality and non-fatal cardiovascular events. In subgroup analyses, mortality benefits were only evident in people at higher risk. Some methods were not well described and it was possible that studies were missed. The conclusions may need to be treated with some caution.

Authors' objectives

To evaluate the cardioprotective effects of dietary supplements of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) when used for one year or longer.


MEDLINE was searched from 1966 to December 2008. Search terms were provided. EMBASE and Cochrane Database of Systematic Reviews were searched and bibliographies of selected papers and reviews were checked. No language restrictions were applied.

Study selection

Randomised controlled trials (RCTs) that assessed the effects of at least one year use of EPA and DHA dietary supplements compared to placebo and that reported on cardiovascular death and at least one secondary outcome were eligible for inclusion. Secondary outcomes were sudden death, all-cause mortality, nonfatal cardiovascular events (unstable angina, myocardial infarction, cardiac failure, arrhythmias). The included studies included people with coronary artery disease, acute myocardial infarction, peripheral vascular disease, with implantable cardioverter defibrillators (ICD), congestive heart failure or hypercholesterolaemia. Most studies used EPA and DHA; two used EPA alone. Dosages ranged from 0.27g to 4.8g per day. Controls were olive oil, non-oil placebo, control plus vitamin E, mixed fatty acids, sunflower oil, corn oil and olive oil. Length of study ranged from one to 4.6 years.

Two authors independently searched for studies.

Assessment of study quality

The authors did not explicitly state how validity was assessed, but they extracted data related to methods of randomisation, blinding and concealment of allocation.

Data extraction

Odds ratio (OR) with 95% confidence interval (CI) were calculated for each outcome.

Two authors independently extracted data. Disagreements were resolved by discussion.

Methods of synthesis

Heterogeneity was assessed using the Cochran Q statistic and I2. Where heterogeneity was insignificant, a fixed-effect method was used to calculate pooled OR and 95% CI. Where significant heterogeneity was present, a random-effects model was used.

Subgroup analyses were performed according to risk of cardiovascular death (high risk: recent acute myocardial infarction, cardiac failure, implanted cardioverter defibrillator versus moderate risk: primary and secondary prevention in people with stable atherosclerotic disease or with hypercholesterolaemia).

Metaregression was used to investigate the relationship between treatment effect and dose.

Results of the review

Eleven RCTs (39,044 participants) were included. Study size ranged from 59 to 18,645. Three studies contributed approximately 94% of the participants. All 11 studies reported random allocation. Nine studies (9,065 participants) were double blinded with allocation concealment; the two largest studies (29,979 participants) were not.

Dietary supplement of EPA/DHA reduced the risk of cardiovascular death (OR 0.87, 95% CI 0.79 to 0.95; 11 trials), sudden cardiac death (OR 0.87, 95% CI 0.76 to 0.99; six trials), all-cause mortality (OR 0.92, 95% CI 0.85 to 0.99; 11 trials) and non-fatal cardiovascular events (OR 0.92 95% CI 0.85 to 0.99; nine trials). All except one study in the sudden cardiac death analysis were in high-risk people. For other mortality outcomes, subgroup analyses showed that benefits were only evident in the high-risk groups. For non-fatal cardiovascular events, benefit was evident only in the moderate-risk group. There was no evidence of statistical heterogeneity for any analysis.

Meta-regression showed that there was no association between dose and treatment effect.

Authors' conclusions

Dietary supplements of omega-3 fatty acids decreased cardiac deaths, non-fatal cardiovascular events and all-cause mortality. The benefits were most apparent in high-risk people.

CRD commentary

The inclusion criteria for the review in terms of study design, interventions and outcomes were clearly stated. The search covered several relevant sources, although it appeared that no systematic searches were made for unpublished studies. It was possible that publication bias may have affected the review. The search was not limited by language, with was likely to have reduced the risk of language bias. The methods of study selection and data extraction were aimed at reducing reviewer error or bias. It appeared that study quality was assessed, although this was not used to inform the analyses. The methods of analyses were appropriate. Little information was given about the participants in the included studies and this may have affected the generalisability of the results. The authors excluded studies that did not report at least two of the outcomes of interest, but did not state how many studies that reported on one outcome only were excluded for this reason; it was not possible to say whether this could have affected the results of the review. In view of these comments, the conclusions may need to be treated with some caution.

Implications of the review for practice and research

Practice: The authors stated that dietary supplementation with omega-3 fatty acids should be considered in the secondary prevention of cardiovascular events. The optimal daily dose was unclear, but low dose (1g/day) was effective and should be considered the preferred dose.

Research: The authors stated that data from large-scale trials were needed to assess the effects of omega-3 fatty acids on well-defined groups at risk of various arrhythmias.


Not stated.

Bibliographic details

Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clinical Cardiology 2009; 32(7): 365-372. [PubMed: 19609891]

Indexing Status

Subject indexing assigned by NLM


Cardiovascular Diseases /drug therapy /etiology /mortality /prevention & control; Dietary Supplements; Docosahexaenoic Acids /administration & dosage; Eicosapentaenoic Acid /administration & dosage; Evidence-Based Medicine; Humans; Odds Ratio; Prospective Studies; Randomized Controlled Trials as Topic; Recurrence /prevention & control; Risk Assessment; Risk Factors; Secondary Prevention; Treatment Outcome



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

Copyright © 2014 University of York.
Bookshelf ID: NBK78278


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