TABLE 1.
Characteristics of included studies.
| References | Registration | Design | Location | Duration | Group | Sample (n) | Male | Age (Year) mean (SD) | BMI (kg/m2) Mean (SD) | Endpoints | Mean baseline TG level (mg/dl) | Diet |
| Bays et al. (29) | NCT01047683 | RCT M D |
Worldwide | 12-week | Placebo※ EPA 4 g/days |
76 76 |
76% 77% |
53.4 (8.3) 51.9 (10.3) |
31.0 (4.3) 30.4 (4.3) |
TG, TC, HDL-C, LDL-C, VLDL-C, non-HDL-C, Apo-B | 703.0 679.5 |
Maintain the National Cholesterol Education Program Therapeutic Lifestyle Changes Diet |
| Bays et al. (11) | NCT01893515 | RCT M D |
USA | 12-week | Placebo (Miglyol 812) EPA 0.6 g/days |
43 41 |
71% 67% |
51.6 (11.4) 53.5 (8.8) |
32.3 (4.6) 31.7 (4.4) |
TG, TC, HDL-C, LDL-C, VLDL-C, non-HDL-C, Apo-B, Apo-AI | 727.4 681.3 |
Maintain the National Cholesterol Education Program Therapeutic Lifestyle Changes diet |
| Chan et al. (30) | NR | RCT D |
Australia | 6-week | Placebo (corn coil) EPA/DHA 4 g/days Atorvastatin 40 mg/days Atorvastatin 40 mg + EPA/DHA 4 g/days |
13 13 14 12 |
NR | 50 (2.5) 58 (2.2) 52 (2.7) 53 (2.6) |
32.4 (0.8) 35.2 (1.2) 34.5 (1.3) 32.5 (0.8) |
TG, TC, HDL-C, LDL-C, non-HDL-C, Apo-B, Apo-AI | 265.8 177.2 168.3 177.2 |
Continue their habitual diet and to keep physical exercise constant |
| Contacos et al. (31) | NR | RCT S |
Australia | 6-week | Placebo※ EPA/DHA 3 g/days |
11 10 |
90% 36% |
64 (7.0) 54 (11.0) |
24.9 (2.3) 27.1 (2.7) |
TG, TC, HDL-C, LDL-C, Apo-B, Apo-AI | 425.3 407.6 |
NR |
| Davidson et al. (32) | NR | RCT D |
USA | 6-week | Placebo (vegetable oil) DHA 3 g/days |
8 9 |
50% 89% |
57 (11.3) 58 (12.0) |
28.5 (5.1) 27.8 (3.0) |
TG, HDL-C, LDL-C, non-HDL-C | 236.0 296.0 |
Keep an National Cholesterol Education Program Step I diet |
| Kastelein et al. (18) | NCT01242527 | RCT M D |
Worldwide | 12-week | Placebo (olive oil) EPA/DHA 4 g/days |
99 99 |
78% 72% |
50.8 (10.6) 52.9 (10.9) |
30.4 (4.3) 31.0 (5.1) |
TG, TC, LDL-C, HDL-C, non-HDL-C, VLDL-C, Apo-B, Apo-AI | 682.0 655.0 |
Follow the National Cholesterol Education Program Therapeutic Lifestyle Changes (TLC) diet |
| Kelley et al. (33) | NR | RCT D |
USA | 14-week | Placebo (olive oil) DHA 3 g/days |
17 17 |
NR | 53.1 (4.1) 55.0 (8.2) |
30.6 (3.3) 27.8 (2.9) |
TG, TC, LDL-C, HDL-C | 240.1 225.9 |
Continue regular diets and activity levels throughout the study. |
| Khandelwal et al. (34) | ETH 2006/N46 | RCT D |
India | 4-week | Placebo (safflower-seed oil) EPA/DHA 2 g/days |
46 40 |
89% 95% |
46.1 (6.1) 48.2 (5.7) |
24.3 (3.4) 25.7 (3.8) |
TG, TC, LDL-C, HDL-C, Apo-B, Apo-AI |
140.9 165.7 |
Maintain habitual diet and lifestyle |
| Koh et al. (35) | NR | RCT S |
Korea | 8-week | placebo※ EPA/DHA 2 g/days |
49 50 |
59% 56% |
54 (7.0) 55 (7.1) |
25.1 (2.3) 25.5 (2.5) |
TG, TC, LDL-C, HDL-C, non-HDL-C, Apo-B, Apo-AI | 267.0 290.0 |
Maintain a low fat diet |
| Maki et al. (12) | NR | RCT M D |
USA | 8-week | Placebo (olive oil) EPA 2 g/days |
53 52 |
62% 52% |
54.4 (10.1) 49.1 (11.8) |
30.6 (5.1) 31.7 (5.8) |
TG, TC, LDL-C, HDL-C, non-HDL-C | 251.5 236.8 |
Maintain consistent dietary habits |
| Mori et al. (36) | NR | RCT D |
Australia | 6-week | placebo (olive oil) EPA 4 g/days DHA 4 g/days |
20 19 17 |
NR | 48.4 (8.9) 48.9 (7.4) 49.1 (9.1) |
28.4 (2.2) 29.0 (3.1) 28.9 (2.9) |
TG, TC, LDL-C, HDL-C | 180.7 178.1 199.4 |
Maintain their usual diets, physical activities, lifestyle |
| Mozaffarian et al. (23)¶ |
NCT03398005 NCT03361501 |
RCT M D |
Worldwide | 26-week | Placebo (cornstarch) EPA/DHA 1.24 g/days |
148 372 |
68% 64% |
53.9 (11.8) 55.3 (10.9) |
31.5 (5.5) 31.5 (5.1) |
TG, LDL-C, HDL-C, non-HDL-C, VLDL-C | 706.0 699.0 |
Maintain the National Cholesterol Education Program Therapeutic Lifestyle Changes Diet |
| Nicholls et al. (19) | NCT02104817 | RCT M D |
worldwide | 48-week | Placebo (corn oil) EPA/DHA 4 g/days |
6539 6539 |
65% 65% |
62.5 (9.0) 62.5 (9.0) |
32.2 (5.6) 32.2 (5.7) |
TG, TC, LDL-C, HDL-C, non-HDL, Apo-B | 246.4 247.0 |
Maintain stable diet |
| Oelrich et al. (37) | NR | RCT D |
USA | 12-week | Placebo (soy oil) EPA/DHA 4 g/days |
15 42 |
93% 71% |
52 (10.0) § | 27 (3.0) 27 (4.0) |
TG, LDL-C | 230.4 248.1 |
Maintain weight and habitual dietary and exercise habits |
| Oh et al. (13) | NR | RCT S |
Korea | 8-week | Placebo※ EPA/DHA 4 g/days |
42 44 |
55% 52% |
54 (9.0) 55 (8.0) |
26.50 (2.7) 26.18 (3.2) |
TG, TC, HDL-C, LDL-C, non-HDL-C, Apo-B, Apo-AI | 281.0 287.0 |
Maintain a low fat diet |
| Schuchardt et al. (38) | NR | RCT M D |
German | 24-week | Placebo (corn oil) EPA/DHA 1.68 g/days |
35 39 |
34% 56% |
62 (8.2) 61.6 (7.5) |
26 (3.3) 25.8 (3.0) |
TG, TC, HDL-C, LDL-C | 133.8 154.2 |
Maintain their usual exercise and dietary habits |
| Shidfar et al. (39) | NR | RCT D |
Iran | 10-week | Placebo (linoleic acid) EPA/DHA 2 g/days |
25 25 |
48% 48% |
54.1 (11.1) 53.4 (11.7) |
29.0 (0.7) 28.4 (0.5) |
TG, TC, HDL-C, LDL-C, Apo-AI, Apo-B | 306.4 299.2 |
Maintain their usual diet and physical activity level |
| Shidfar et al. (40) | NR | RCT D |
Iran | 10-week | Placebo (linoleic acid) EPA 1 g/days |
19 16 |
37% 31% |
54.4 (12.2) 54.4 (11.7) |
27.6 (3.0) 26.9 (2.2) |
TG, TC, HDL-C, LDL-C, Apo-AI, Apo-B | 311.5 304.0 |
Maintain their usual diets, physical activities, and lifestyle |
| Su et al. (14) | NCT017256 | RCT M D |
China | 8-week | Placebo (olive oil) EPA/DHA 4 g/days |
87 84 |
74% 66% |
54.4 (10.7) 53.7 (11.0) |
26.7 (3.9) 26.6 (3.7) |
TG, TC, HDL-C, LDL-C, non-HDL-C | 336.9 351.2 |
Keep a low fat diets |
| Ballantyne et al. (41) | NCT01047501 | RCT M D |
USA | 12-week | statin+Placebo※ statin+EPA 4 g/days |
233 233 |
62% 61% |
61.2 (10.1) 61.1 (10.0) |
33.0 (5.0) 32.7 (5.0) |
TG, TC, HDL-C, LDL-C, non-HDL-C, VLDL-C, Apo-B | 259.0 264.8 |
Maintain stable diet and exercise |
| Bays et al. (42) | NCT00435045 | RCT M D |
USA | 16-week | Atorvastatin+Placebo (corn oil) Atorvastatin+EPA/DHA 4 g/days |
122 123 |
58% 58% |
56 (10.8) 56.3 (9.6) |
31.0 (4.0) 30.2 (4.6) |
TG, TC, HDL-C, LDL-C, non-HDL-C, VLDL-C, Apo-B, Apo-A1 | 339.0 345.5 |
Follow the National Cholesterol Education Program therapeutic lifestyle changes diet |
| Davidson et al. (43) | NCT00246701 | RCT M D |
USA | 8-Week | Simvastatin 40 mg/days+Placebo (vegetable oil) Simvastatin 40 mg+EPA/DHA 4 g/days |
132 122 |
61% 54% |
59.3 (10.8) 60.3 (10.1) |
31.5 (5.5) 31.0 (5.4) |
TG, TC, LDL-C, HDL-C, VLDL-C, non-HDL-C, Apo-B | 286.7 282.0 |
Participants received dietary counseling on the Therapeutic Lifestyle Changes diet |
| Durringt on et al. (44) | NR | RCT D |
UK | 24-week | Simvastatin+Placebo (corn oil) Simvastatin+EPA/DHA 4 g/days |
29 30 |
69% 77% |
54.8 (10.2) 55.2 (7.0) |
28.4 (4.2) 28.8 (2.8) |
TG, TC, HDL-C, LDL-C, VLDL-C, Apo-B, Apo-AI | 407.6 336.7 |
Patients received dietary advice and maintained their diet unchanged throughout the trial |
| Jun et al. (20) | NCT03482180 | RCT M D |
Korea | 8-week | Atorvastatin 20 mg+placebo (olive oil) Atorvastatin 20 mg+EPA/DHA 4 g/days |
103 97 |
63% 66% |
58.0 (11.4) 58.7 (10.1) |
27.0 (3.4) 27.3 (3.5) |
TG, TC, VLDL-C, LDL-C, HDL-C, non-HDL-C, Apo-B, Apo-AI | 293.0 298.5 |
NR |
| Kim et al. (45) | NCT03026933 | RCT M D |
Korea | 8-week | Rosuvastatin 20 mg/days+placebo※ Rosuvastatin 20 mg/days+EPA/DHA 4 g/days |
104 97 |
64% 61% |
56.6 (10.5) 59.7 (10.8) |
27.6 (3.6) 27.4 (3.7) |
TG, TC, VLDL-C, LDL-C, HDL-C, non-HDL-C, Apo-B, Apo-AI | 279.6 284.0 |
NR |
| Lee et al. (46) | NR | RCT O M |
Korea | 8-week | Statin+no placebo Statin+EPA/DHA 4 g/days |
17 17 |
NR | 56§(mean) | 25.7§(mean) | TG, TC, LDL-C, HDL-C, Apo-B, Apo-AI | 321.5 295.7 |
NR |
| Maki et al. (21) | NCT01408303 | RCT M D |
USA | 6-week | Statin+placebo (olive oil) Statin+EPA/DHA 4 g/days |
216 216 |
57% 63% |
61.5 (9.6) 60.1 (9.2) |
32.7 (5.3) 33.3 (6.6) |
TG, TC, VLDL-C, LDL-C, HDL-C, non-HDL-C, Apo-B, Apo-AI | 280.0 287.0 |
Maintain stable diet |
| Meyer et al. (47) | NR | RCT | Australia | 24-week | Statin+Placebo (olive oil) Statin+EPA/DHA 2.72 g/days |
15 15 |
67% 67% |
59 (7.7) 53 (19.4) |
27.9 (4.6) 26.2 (0.8) |
TG, TC, HDL-C, LDL-C | 179.0 209.1 |
NR |
| Ng et al. (48) | NR | RCT D |
Australia | 6-week | Atorvastatin+Placebo (corn oil) Atorvastatin40 mg+EPA/DHA 4 g/days |
13 11 |
NR | 52 (10.8) 54 (6.6) |
34.5 (5.0) 32.5 (3.0) |
TG, TC, LDL-C, HDL-C, non-HDL-C, Apo-B, Apo-AI | 166.6 181.6 |
NR |
| Nomura et al. (49) | NR | RCT | Japan | 24-week | Pitavastatin 2 mg+no Placebo Pitavastatin 2 mg+EPA 1.8 g/days |
64 72 |
53% | 65 (3.0)§ | 27.3 (3.9)§ | TC, TG, HDL-C, LDL-C | 198.0 248.0 258.0 |
NR |
| Nordøy et al. (50) | NR | RCT D |
Norway | 5-week | Simvastatin 20 mg+placebo (corn oil) Simvastatin 20 mg+EPA/DHA 4 g/days |
20 21 |
70% 71% |
46.7 (7.8) 46.8 (9.2) |
28.8 (3.7) 27.6 (4.0) |
TG, TC, HDL-C, Apo-B, Apo-AI | 268.5 244.5 |
Follow guidelines aiming at a dietary composition |
| Woo et al. (24) | NR | RCT M D |
Korea | 8-week | Atorvastatin 40 mg+placebo (UI-018) atorvastatin 40 mg+EPA 4 g/days |
99 101 |
74% 88% |
60.0 59.0 (mean) |
25.5 (2.9) 26.8 (2.6) |
TG, TC, VLDL-C, LDL-C, HDL-C, non-HDL-C, Apo-B, Apo AI | 297.1 294.2 |
NR |
NR, not report; RCT, randomized controlled trial; D, double-blinded; S, single-blinded; M, multicenter; O, open-label.
¶: The study pooled the results of two identical trials.
※: The type of placebo is unknown.
§: These values cover all participants.