Table 1.
Comparison of three major trials of omega-3 fatty acids reported in 2018. ASCEND: A Study of Cardiovascular Events in Diabetes; VITAL: Vitamin D and Omega-3 Trial; REDUCE-IT (the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial; CVD: cardiovascular disease; TG: triglycerides; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; CHD: coronary heart disease
| RANDOMIZED CONTROLLED TRIAL | COUNTRY | SAMPLE SIZE/SUBJECT TYPE | YEARS OF FOLLOW-UP | EPA+DHA DOSE | FINDINGS |
|---|---|---|---|---|---|
| ASCEND5 | United Kingdom | 15,480/patients with type 2 diabetes | 7.4 | 840 mg | Composite end point not significantly altered |
| Risk for vascular death ↓ by 19% (95% CI, 1%–33%) | |||||
| VITAL4 | United States | 25,871/older adults without history of CVD or cancer | 5.3 | 840 mg | Composite end point not significantly altered |
| Risk for heart attack ↓ by 28% (95% CI, 10%–41%) | |||||
| Risk for total CHD ↓ by 17% (95% CI, 3%–29%) | |||||
| REDUCE-IT6 | International (11 countries) | 8,179/statin-treated patients with median TG levels of 216 mg/dL and other CVD risk factors | 4.9 | 3,600 mg (EPA only) | Primary CVD end point ↓ by 26% |
| Significant reductions in several secondary end points |
Table 2.
Study design and primary results from clinical trials assessing the effects of long-chain omega-3 fatty acid interventions on cardiovascular disease events. CV: cardiovascular; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; MI: myocardial infarction; CVD: cardiovascular disease; ALA: alpha-linolenic acid
| TRIAL, YEAR | OMEGA-3 INTERVENTION | CONTROL | STUDY POPULATION | DURATION (YEARS) | PRIMARY OUTCOME(S) | |
|---|---|---|---|---|---|---|
| Diet and Reinfarction Trial (DART) 1989 19,20 | Dietary advice to consume ≥2 servings of fatty fish per week | No dietary advice | Men recovered from MI (N = 2,033) | 2 | Ischemic heart disease events (ischemic heart disease death and nonfatal MI) | RR: 0.84 95% CI, 0.66–1.07 |
| Supplement subgroup: 3 g/d of fish oil (~840 mg/d EPA+DHA)* | ||||||
| Total mortality | RR: 0.71 95% CI, 0.54–0.93 | |||||
| Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto micardico Prevenzione (GISSI-P) 1999 21 | 840 mg/d EPA+DHA as ethyl esters | Standard of care | Adults with previous MI in last 3 months (N = 11,323) | 3.5 | Death, nonfatal MI, nonfatal stroke | RR: 0.90 95% CI, 0.82–0.99 |
| CV death, nonfatal MI, nonfatal stroke | RR: 0.89 95% CI, 0.80–1.01 | |||||
| Japan EPA Lipid Intervention Study (JELIS) 2007 22 | 1,800 mg/d EPA as ethyl esters with statin | Statin only (no omega-3 fatty acids) | Adults with hypercholesterolemia, with or without a history of coronary artery disease (MI > 6 months) (N = 18,645) | 4.6 | Major coronary event (sudden cardiac death, fatal and nonfatal MI, and other nonfatal events) | HR: 0.81 95% CI, 0.69–0.95 |
| Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure (GISSI-HF), 2008 23 | 840 mg/d EPA+DHA as ethyl esters | Unspecified placebo oil | Adults with chronic heart failure (N = 6,975) | 3.9 | All-cause mortality | HR: 0.91 95.5% CI, 0.833–0.998 |
| All-cause mortality or hospitalization for CVD | HR: 0.92 99% CI, 0.849–0.999 | |||||
| Alpha Omega 2010 24 | Margarine containing 226 mg EPA and 150 mg DHA | Placebo or ALA-containing margarine | Adults with MI within 10 years (N = 4,837) | 3.4 | Major CV events (fatal and nonfatal cardiovascular events and cardiac interventions) | HR: 1.01 95% CI, 0.87–1.17 |
| OMEGA 2010 25 | 840 mg/d EPA+DHA as ethyl esters | Olive oil placebo | Adults with acute MI (3–14 days) (N = 3,851) | 1 | Sudden cardiac death | OR: 0.95 95% CI, 0.56–1.60 |
| Supplmentation en Folates et Omega-3 (SU.FOL.OM3) 2010 26 | 600 mg/d EPA+DHA at a ratio of 2:1 | Placebo | Adults with acute coronary or cerebral ischemic event within < 1 year (N = 2,501) | 4.7 | Major CV events (composite of nonfatal MI, stroke, or death from CVD) | HR: 1.08 95% CI, 0.79–1.47 |
| Outcome Reduction with an Initial Glargine Intervention (ORIGIN) 2012 27 | 840 mg/d EPA+DHA as ethyl esters | Olive oil placebo | Adults with CVD plus dysglycemia (N = 12,536) | 6.2 | Death from CVD | HR: 0.98 95% CI, 0.87–1.10 |
| Risk and Prevention (R&P) 2013 28,29 | 840 mg/d EPA+DHA as ethyl esters | Olive oil placebo | Adults with high CVD risk without previous MI (N = 12,513) | 5 | Death or hospitalization from CVD | HR: 0.98 95% CI, 0.88–1.08 |
| Age-Related Eye Disease Study 2 (AREDS2) 2014 30 | 350 mg DHA and 650 mg EPA | Corn oil placebo | Adults with intermediate or advanced age-related macular degeneration in one eye (N = 4,203) | 4.8 | CVD mortality (sudden death, death due to MI, heart failure, or stroke) and CVD morbidity (MI, stroke, unstable angina, coronary and carotid revascularization, hospitalized congestive heart failure, resuscitated cardiac arrest) | HR: 0.95 95% CI, 0.78–1.17 |