Table 1.
Review of large-scale clinical trials of omega-3 polyunsaturated fatty acids.
| Study | GISSI-P | JELIS | GISSI-HF | ORIGIN | SU.FOL.OM3 | ASCEND | VITAL | REDUCE-IT |
|---|---|---|---|---|---|---|---|---|
| Subjects | Post MI (< 3 mo) | T-C ≥6.5 mmol/L1, or LDL-C ≥4.4 mmol/L | Chronic heart failure (NYHA class II–IV) | ≥50 y, diabetes or prediabetes, and high risk of CVD | MI, unstable angina, and ischemic stroke | ≥40 y, with diabetes mellitus, and without CVD | Men ≥50 y, women ≥55 y | ≥45 y with established CVD or ≥50 y with diabetes and ≥1 additional RF, and with fasting TG level of 1.69 to 5.63 mmol/L, LDL-C, 1.06 to 2.59 mmol/L, and had been treated with statins for ≥4 weeks |
| Components of n-3 agents | EPA/DHA | EPA | EPA/DHA | EPA/DHA | EPA/DHA | EPA/DHA | EPA/DHA | EPA |
| Dosage (g/day) | 1 | 1.8 | 1 | 1 | 0.6 | 1 | 1 | 4 |
| No. of subjects | 11,324 | 18,645 | 6975 | 12,536 | 2501 | 15,480 | 25,871 | 8179 |
| Enrollment period | 1993–1995 | 1996–1999 | 2002–2005 | 2003–2005 | 2003–2007 | 2005–2011 | 2011–2014 | 2011–2016 |
| Follow-up (median, y) |
3.5 | 4.6 | 3.9 | 6.2 | 4.7 | 7.4 | 5.3 | 4.9 |
| Primary endpoints | All-cause death, non-fatal MI, and non-fatal stroke | Major coronary event(b) | All-cause death | Cardiovascular death | Non-fatal MI, ischemic stroke, and | Non-fatal MI, stroke, TIA, and vascular death excluding ICH | Major cardiovascular events(e) | Cardiovascular death, non-fatal MI, nonfatal stroke, coronary revascularization, and unstable angina |
| n-3 PUFA treatment results for PE, HR or RR (95% CI) | 0.85 (0.74–0.98) (a) | 0.81 (0.69–0.95) | 0.91 (0.833–0.998) | 0.98 (0.87–1.10) | 1.08 (0.79–1.47) | 0.97 (0.87–1.08) | 0.92 (0.80–1.06) | 0.75 (0.68–0.83) |
| Stroke outcome | Fatal and non-fatal stroke | Fatal and non-fatal stroke | Fatal and non-fatal stroke | Fatal and non-fatal stroke | Fatal and non-fatal stroke, and death from cardiovascular diseases | Non-fatal ischemic stroke | Fatal and non-fatal stroke | Fatal and non-fatal stroke |
| n–3 PUFA treatment results for SO, HR or RR (95% CI) | 0.95 (0.61–1.47) (a) | 1.08 (0.95–1.72) (c) | 1.16 (0.89–1.51) | 0.92 (0.79–1.08) | 1.04 (0.62–1.75) | 1.01 (0.84–1.22) | 1.04 (0.83–1.31) | 0.72 (0.55–0.93) |
| 0.8 (0.64–0.997) (d) | ||||||||
| Reference number | [44] | [51,52] | [45,46] | [48] | [47] | [50] | [49] | [53,54] |
MI = myocardial infarction, mo = month, T-C = total cholesterol, LDL-C = low-density lipoprotein cholesterol, y = years, NYHA = New York Heart Association, CVD = cardiovascular disease, RF = risk factors, TG = triglyceride, EPA = eicosapentaenoic acid, DHA = docosahexaenoic acid, TIA = transient ischemic attack, ICH = intracranial hemorrhage, PUFAs = polyunsaturated fatty acids, PE = primary endpoint, HR = hazard ratio, RR = risk ratio, CI = confidence interval, SO = stroke outcome. (a) = calculated by four-way analysis. (b) = sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. (c) = subgroup of primary prevention for stroke (n = 17,703). (d) = subgroup of secondary prevention for stroke (n = 942). (e) = myocardial infarction, stroke, and death from cardiovascular causes.