PRACTICE CHANGER
Stop recommending omega-3 fatty acid supplements for cardiovascular protection. They have no significant impact on all-cause mortality, acute myocardial infarction, sudden death, or stroke.1
Strength of Recommendation
A: Based on a meta-analysis of randomized controlled trials (RCTs).
Rizos E, Ntzani E, Bika E, et al. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308:1024-1033.
ILLUSTRATIVE CASE
A 59–year-old patient who had a myocardial infarction (mi) 3 years ago is taking an ace inhibitor, a statin, and a b-blocker. He asks you whether he should also take omega-3 fatty acid supplements to further decrease his risk of heart disease. What should you tell him?
Coronary artery disease (CAD) kills more than 500,000 Americans every year2, and medical and dietary therapies for primary and secondary cardiovascular protection are paramount. Omega-3 polyunsaturated fatty acid (PUFA) supplementation is one such therapy. Omega-3 PUFAs are precursors to certain prostaglandins that decrease the proinflammatory state in patients with CAD. They also lower triglyceride levels and produce an antiarrhythmic effect by promoting electrical stability.
But do PUFA supplements provide cardioprotection?
The American Heart Association’s Nutrition Committee recommends either omega-3 PUFA supplementation with 250 to 500 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day or 2 servings of oily fish per week for both primary and secondary prevention of CAD.3 The European Society of Cardiology also encourages increased consumption of oily fish.4
These recommendations are based on primary and secondary prevention studies, performed between 1989 and 2007, that found a 15% to 29% decrease in all-cause mortality and nonfatal cardiovascular events associated with regular intake of omega-3 fatty acids.5-7 The systematic review and meta-analysis detailed below revisited the effect of omega-3 supplementation on major cardiovascular outcomes.1
STUDY SUMMARY: Omega-3 supplements don’t lower cardiovascular risk
This meta-analysis included 20 RCTs with a total of 68,680 patients. The median age was 68 years, with a range from 49 to 70 years. Thirteen of the studies evaluated omega-3 PUFAs for secondary prevention of cardiovascular outcomes, 4 assessed both primary and secondary prevention, and 3 looked at outcomes in patients with implantable cardioverter defibrillators. All lasted longer than one year, and most were high quality, with a low risk of bias.
The median treatment duration was 2 years, with a maximum of 6.2 years. The mean omega-3 PUFA dose evaluated in the studies was 1.5 g per day, with the exception of 2 studies in which patients received omega-3 PUFAs through dietary sources. Twelve studies used a dose of 1 g or more per day. Half of the included trials were performed during the period when statins were routinely prescribed for cardiovascular risk modification (1998 or later).
Outcomes included all-cause mortality (17 studies), cardiac death (13 studies), sudden death (7 studies), MI (13 studies), and stroke (9 studies).
This meta-analysis found trends toward a decrease in all-cause mortality, cardiac death, sudden death, and MI in patients taking omega-3 PUFAs, but no statistically significant association between any of the outcomes and omega-3 PUFA supplementation. The relative risk for all-cause mortality was 0.96 (95% confidence interval, 0.91-1.02; P=.17). Prespecified subgroup analysis found no association between treatment effect and omega-3 fatty acid dose.
Are dietary sources of omega-3s more effective?
In the 2 trials involving dietary supplementation with omega-3 PUFAs, the results for all-cause mortality and cardiac death were conflicting, with one showing an increase in all-cause mortality and cardiac death and the other showing a decrease in both outcomes compared with the control group. No harmful effects of omega-3 PUFAs were found in either the supplement- or diet-based studies.
