Table 3.
Cardiovascular outcomes trials of omega-3 fatty acids.
| Trial | Intervention | Patient Population | Statin Use | Primary Endpoint | Primary Endpoint Met? | HR/OR/RR for Intervention |
|---|---|---|---|---|---|---|
| Trials of DHA+EPA combinations | ||||||
| GISSI Prevenzione [51] | 1 g omega-3 fatty acids (EPA:DHA in a 1:2 ratio) vs no supplement for secondary prevention | 11,324 patients within 3 months after MI; no lipid level–based inclusion criteria | Not established as preventive care standard at time of study | Co-primary endpoints: (1) death, non-fatal MI, and non-fatal stroke; (2) CV death, non-fatal MI, and non-fatal stroke | Yes | (1) RR 0.85; 95% CI 0.74–0.98 (2) RR 0.80; 95% CI 0.68–0.95 |
| OMEGA [10] | 1 g omega-3 fatty acids (DHA 380 mg + EPA 460 mg) vs 1 g olive oil for secondary prevention | 3851 patients who had experienced acute MI within 3–14 days of randomization; no lipid level–based inclusion criteria | >90% on statins at discharge post-MI | Sudden cardiac death | No | OR 0.95; 95% CI 0.56–1.60; P = 0.84 |
| VITAL [12] | 1 g omega-3 fatty acid (DHA 380 mg + EPA 460 mg) vs placebo for primary prevention | 25,871 men ≥50 years of age or women ≥55 years of age; no lipid level–based inclusion criteria | ~35% on statins | MI, stroke, and CV death | No | HR 0.92; 95% CI 0.80–1.06; P = 0.24 |
| ASCEND [11] | Omega-3 fatty acids (DHA 380 mg + EPA 460 mg) vs placebo | 15,480 diabetic patients aged ≥40 years, but with no evidence of CV disease; no lipid level–based inclusion criteria | ~75% on statins | Serious vascular events | No | RR 0.97; 95% CI 0.87–1.08; P = 0.55 |
| Trials of EPA alone | ||||||
| JELIS [60] | EPA 1.8 g/day + statin vs statin alone for primary and secondary prevention | 5859 men aged 40–75 years and 12,786 postmenopausal women up to 75 years with hypercholesterolemia (total cholesterol ≥251 mg/dL; corresponding to LDL-C ≥170 mg/dL) | 98% on statins | Major coronary events including sudden cardiac death, fatal and non-fatal MI, unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting | Yes | HR 0.81; 95% CI 0.69–0.95; P = 0.011 |
| REDUCE-IT [14] | Icosapent ethyl 4 g/day + statin vs placebo + statin | 8179 adults aged ≥45 years with established CV disease or ≥50 years with type 2 diabetes and ≥1 additional CV event risk factor; TG 135–499 mg/dL and LDL-C 41–100 mg/dL | >99% on statins | Composite of CV death, non-fatal MI, non-fatal stroke, coronary revascularization, or unstable angina in a time-to-event analysis | Yes | HR 0.75; 95% CI 0.68–0.83; P < 0.001 |
ASCEND, A Study of Cardiovascular Events in Diabetes; CI, confidence interval; CV, cardiovascular; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; GISSI-Prevenzione, Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico; HR, hazard ratio; JELIS, Japan EPA Lipid Intervention Study; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; OMEGA, Randomized, Placebo-Controlled Trial to Test the Effect of Highly Purified Omega-3 Fatty Acids on Top of Modern Guideline-Adjusted Therapy After Myocardial Infarction; OR, odds ratio; REDUCE-IT, Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial; RR, rate ratio; TG, triglycerides; VITAL, Vitamin D and Omega-3 Trial.