Table 1.
Main clinical trials focused on the effect of n-3 PUFAs on cardiovascular events (created partly on information and data from [25]).
| Type of Intervention | Main Characteristics | Clinical Effect Including Adverse Events | |
|---|---|---|---|
| Successful—primary endpoint reached | |||
| REDUCE-IT [8] | Icosapent ethyl 4 g/day, mineral oil as control | Patients with established CVD or DM on statin therapy with increased TG (n = 8179; 29% women, FU 4.9 years), median TG 216 mg/dL (2.44 mmol/L) | The risk of CV death, MI, revascularization, unstable angina was significantly lower in treated patients (26% reduction). The incidence of atrial fibrillation and peripheral edema were significantly higher in the treatment group. The overall rates of serious adverse bleeding were similar. No fatal bleedings and no between-group differences in the rates of hemorrhagic stroke, serious central nervous system bleeding, or gastrointestinal bleeding. |
| EVAPORATE [9] | Icosapent ethyl 4 g/day, mineral oil as control | Patients with confirmed coronary artery stenosis, on statin therapy with increased TG (n = 80; 44 women, FU 1.5 year), median TG 191–200 mg/dL (2.48–2.60 mmol/L) | Low-attenuation plaque volume and thickening of fibrotic cap were significantly reduced in the treatment group. No serious adverse effects were described. |
| JELIS [10] | EPA 1.8 g/day (+pravastatin or simvastatin), no placebo | Patients with previous MI or PCI or with confirmed angina pectoris or without CVD (n = 18,645; 69% women, FU 4.6 years), TG 150.4 mg/dL (1.7 mmol/L) | All-cause mortality was reduced in secondary, but not in primary prevention. Adverse experiences and discontinuation rate due to treatment was more common in the treatment group, including laboratory data, gastrointestinal disturbances, skin abnormalities, and cerebral and fundal bleedings, epistaxis and subcutaneous bleeding (all mild). Incidence of new cancers was not different between groups. |
| CHERRY [26] | Pitavastatin and EPA therapy (4 mg/day and 1800 mg/day) vs. pitavastatin (4 mg/day), | Patients after PCI, pitavastatin/EPA group (n = 97) vs. pitavastatin group (n = 96), 16–20% women, FU 6–8 months, median TG 105–111 mg/dL (1.2–1.25 mmol/L) | Statin + EPA therapy significantly reduced coronary plaque volume vs. statin therapy alone. Plaque stabilization was reinforced by statin/EPA in patients with stable angina pectoris. No significant difference in adverse events, including atrial fibrillation. |
| Not successful | |||
| ORIGIN [27] | EPA (465 mg) + DHA (375 mg) vs. placebo (approx. 1 g of olive oil). | High risk of CVD + impaired Fasting glucose/glucose intolerance/DM (n = 12,536; 35% women; FU 6.2 years). Median TG 140–142 mg/dL (1.58–1.60 mmol/L) |
No reduction in non-fatal MI or stroke, death from CV cause or arrhythmia was observed. No differences in major bleeding. |
| ASCEND [11] | EPA + DHA combined (1 g/day) vs. olive oil capsule | Persons older than 40 years + DM, without CVD (n = 15,480, FU 7.4 years, 37% female), TG not measured | No effect on non-fatal MI or stroke, vascular death in treated patients. No significant between-group differences in the rates of non-fatal serious adverse events, including new cancers. |
| STRENGTH [12] | EPA + DHA combined (4 g/day) vs. corn oil. | Patients with CVD or at high risk for CVD (n = 13,078; FU 3.5 years, 35% women), median TG 240 mg (2.72 mmol/L) | No significant effect of treatment on CV death, non-fatal MI, stroke, coronary revascularization or unstable angina observed. The incidence of gastrointestinal adverse events was higher in the treatment group. New-onset atrial fibrillation was more common in the treatment group. Major and minor bleeding events were not different between groups. |
| OMEMI [14] | EPA 930 mg + DHA 660 mg vs. corn oil | Age 70 to 82 year + recent (2–8 weeks) acute MI (n = 1014, FU 2 years; 29% females), mean TG 111.4 mg/dL (1.26 mmol/L) | No reduction in clinical events. No differences in major bleeding (10.7% vs. 11.0% in controls). No patients withdrew because of bleeding problems. Reasons for discontinuing treatment not different between the groups (gastrointestinal symptoms, difficulty swallowing capsules, other disease burdens not related to the study intervention). |
| VITAL [28] | Vitamin D3 (2000 IU per day) and 1 g fish-oil capsule (EPA-460 mg, DHA-380 mg) vs. placebo (not specified) | Healthy men > 50 and women > 55 years of age (n = 25,871; FU 5.3 years, 51% women), TG not specified | No effect on MI, stroke, CV death in treated patients was detected; benefit was observed in African Americans (HR: 0.23); PCI (HR: 0.78); fatal MI (HR: 0.50). No excess risks of bleeding or other serious adverse events, including gastrointestinal symptoms, major bleeding episodes observed |
Legend: AF: atrial fibrillation, CV: cardiovascular, CVD: cardiovascular disease, DHA: docosahexaenoic acid, DM: diabetes mellitus, EPA: eicosapentaenoic acid, FU: follow up, HR: hazard ration/CI: confidence intervals, MI: myocardial infarction, PCI: percutaneous coronary intervention.