PRACTICE CHANGER
Stop recommending omega-3 fatty acid supplements for cardiovascular protection. They have no significant impact on all-cause mortality, acute myocardial infarction (MI), sudden death, or stroke.1
STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis of randomized controlled trials (RCTs).
ILLUSTRATIVE CASE
A 59-year-old patient who had an MI three years ago is taking an ACE inhibitor, a statin, and a -blocker. He asks you whether he should also take omega-3 fatty acid supplements to further decrease his risk for heart disease. What should you tell him?
Coronary artery disease (CAD) kills more than 500,000 Americans every year,2 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 anti-arrhythmic 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 of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day or two 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, which 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, with a range of 49 to 70. Thirteen of the studies evaluated omega-3 PUFAs for secondary prevention of cardiovascular outcomes, four assessed both primary and secondary prevention, and three looked at outcomes in patients with implantable cardioverter defibrillators. All lasted longer than one year, and most were high quality, with a low risk for bias.
The median treatment duration was two years, with a maximum of 6.2 years. The mean omega-3 PUFA dose evaluated in the studies was 1.5 g/d, with the exception of two 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 (seven studies), MI (13 studies), and stroke (nine 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. 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 two trials that involved 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.
WHAT’S NEW
More evidence of little benefit
The meta-analysis by Rizos et al is the most up-to-date, comprehensive look at the value of omega-3 fatty acids for primary and secondary prevention of cardiovascular events. It differs from previous reviews in that most of the included studies were well-done RCTs.
In addition, the studies were performed in both primary and secondary cardiovascular disease prevention settings and involved different forms of omega-3 PUFA supplementation, including dietary sources and supplements. The trials were predominantly larger than those included in previous systematic reviews, as well. The baseline risk for cardiovascular disease in the newer studies (seven of the 20 RCTs were completed after 2007) may be different from that of previous studies because of increased use of certain medications, such as statins.
In recent years, other studies of omega-3 PUFAs have had similar results. A meta-analysis of 14 RCTs found that omega-3 PUFA supplementation offered no benefit for the secondary prevention of cardiovascular disease.8 The FORWARD trial—published earlier this year—showed that omega-3 PUFAs did not decrease the recurrence of atrial fibrillation in patients with a history of confirmed paroxysmal atrial fibrillation.9 And an earlier (2006) analysis of RCTs and cohort studies found no benefit from omega-3 fatty acids for primary prevention of cardiovascular disease or cancer.10