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. 2018 Jul 18;2018(7):CD003177. doi: 10.1002/14651858.CD003177.pub3

Comparison 1.

High vs low LCn3 omega‐3 fats (primary outcomes)

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1 All‐cause mortality (overall) ‐ LCn3 39 92653 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.93, 1.03]
2 All‐cause mortality ‐ LCn3 ‐ sensitivity analysis (SA) fixed‐effect 39 90244 Risk Ratio (M‐H, Fixed, 95% CI) 0.97 [0.93, 1.01]
3 All‐cause mortality ‐ LCn3 ‐ SA by summary risk of bias 39 92653 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.93, 1.03]
3.1 Low risk of bias 15 33146 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.94, 1.08]
3.2 Moderate/high risk of bias 24 59507 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.86, 1.03]
4 All‐cause mortality ‐ LCn3 ‐ SA by compliance and study size 38 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
4.1 SA ‐ low risk of compliance bias 18 15654 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.86, 1.14]
4.2 SA ‐ 100+ randomised 35 92397 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.93, 1.03]
5 All‐cause mortality ‐ LCn3 ‐ subgroup by dose 39 92653 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.93, 1.03]
5.1 LCn3 ≤150 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
5.2 LCn3 > 150 ≤ 250 mg/d 1 407 Risk Ratio (M‐H, Random, 95% CI) 0.77 [0.27, 2.18]
5.3 LCn3 > 250 ≤400 mg/d 1 2033 Risk Ratio (M‐H, Random, 95% CI) 0.72 [0.56, 0.92]
5.4 LCn3 > 400 ≤ 2400 mg/d 28 87445 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.93, 1.05]
5.5 LCn3 > 2.4 ≤ 4.4 g/d 7 2486 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.67, 1.70]
5.6 LCn3 > 4.4 g/d 2 282 Risk Ratio (M‐H, Random, 95% CI) 0.33 [0.03, 3.08]
6 All‐cause mortality ‐ LCn3 ‐ subgroup by replacement 39 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
6.1 LCn3 replacing SFA 5 3279 Risk Ratio (M‐H, Random, 95% CI) 0.72 [0.56, 0.92]
6.2 LCn3 replacing MUFA 15 46176 Risk Ratio (M‐H, Random, 95% CI) 0.96 [0.90, 1.02]
6.3 LCn3 replacing N‐6 9 2806 Risk Ratio (M‐H, Random, 95% CI) 0.74 [0.51, 1.09]
6.4 LCn3 replacing CHO 1 281 Risk Ratio (M‐H, Random, 95% CI) 0.52 [0.05, 5.65]
6.5 LCn3 replacing nil/low n‐3 placebo 10 39601 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.86, 1.14]
6.6 LCn3 replacement unclear 3 3593 Risk Ratio (M‐H, Random, 95% CI) 0.91 [0.46, 1.79]
7 All‐cause mortality ‐ LCn3 ‐ subgroup by intervention type 39 92653 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.93, 1.03]
7.1 Dietary advice 3 5554 Risk Ratio (M‐H, Random, 95% CI) 0.90 [0.60, 1.35]
7.2 Supplemental foods 2 5039 Risk Ratio (M‐H, Random, 95% CI) 1.02 [0.84, 1.24]
7.3 Supplements (capsule) 33 81855 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.92, 1.01]
7.4 Any combination 1 205 Risk Ratio (M‐H, Random, 95% CI) 0.65 [0.11, 3.79]
8 All‐cause mortality ‐ LCn3 ‐ subgroup by duration 39 92653 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.93, 1.03]
8.1 Medium duration 1 to < 2 years in study 18 9737 Risk Ratio (M‐H, Random, 95% CI) 1.03 [0.82, 1.30]
8.2 Medium‐long duration: 2 to < 4 years in study 14 29234 Risk Ratio (M‐H, Random, 95% CI) 0.91 [0.86, 0.96]
8.3 Long duration: ≥ 4 years in study 7 53682 Risk Ratio (M‐H, Random, 95% CI) 1.03 [0.98, 1.09]
9 All‐cause mortality ‐ LCn3 ‐ subgroup by primary or secondary prevention 39 92653 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.93, 1.03]
9.1 Primary CVD prevention 17 41202 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.94, 1.08]
9.2 Secondary CVD prevention 22 51451 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.88, 1.04]
10 All‐cause mortality ‐ LCn3 ‐ subgroup by statin use 39 90244 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.92, 1.03]
10.1 LCn3 ‐ ≥50% of control group on statins 8 40500 Risk Ratio (M‐H, Random, 95% CI) 1.02 [0.93, 1.11]
10.2 LCn3 ‐ < 50% of control group on statins 26 46604 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.88, 1.03]
10.3 LCn3 ‐ use of statins unclear 5 3140 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.58, 1.63]
11 Cardiovascular mortality (overall) ‐ LCn3 25 67772 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.03]
12 CVD mortality ‐ LCn3 ‐ SA fixed‐effect 25 67772 Risk Ratio (M‐H, Fixed, 95% CI) 0.94 [0.89, 1.00]
13 CVD mortality ‐ LCn3 ‐ SA by summary risk of bias 25 67772 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.03]
13.1 Low risk of bias 9 29133 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.90, 1.09]
13.2 Moderate/high risk of bias 16 38639 Risk Ratio (M‐H, Random, 95% CI) 0.92 [0.80, 1.05]
14 CVD mortality ‐ LCn3 ‐ SA by compliance and study size 24 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
14.1 SA ‐ low risk of compliance bias 12 13244 Risk Ratio (M‐H, Random, 95% CI) 1.00 [0.82, 1.23]
14.2 SA ‐ 100+ randomised 21 67516 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.04]
15 CVD mortality ‐ LCn3 ‐ subgroup by dose 26 67873 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.03]
15.1 LCn3 ≤ 150 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
15.2 LCn3 > 150 ≤ 250 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
15.3 LCn3 > 250 ≤ 400 mg/d 1 2033 Risk Ratio (M‐H, Random, 95% CI) 0.70 [0.53, 0.91]
15.4 LCn3 > 400 ≤ 2400 mg/d 19 64126 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.89, 1.06]
15.5 LCn3 > 2.4 ≤ 4.4 g/d 4 1432 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.58, 1.77]
15.6 LCn3 > 4.4 g/d 2 282 Risk Ratio (M‐H, Random, 95% CI) 0.33 [0.03, 3.08]
16 CVD mortality ‐ LCn3 ‐ subgroup by replacement 26 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
16.1 N‐3 replacing SFA 3 2537 Risk Ratio (M‐H, Random, 95% CI) 0.69 [0.53, 0.90]
16.2 N‐3 replacing MUFA 12 44242 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.86, 1.04]
16.3 N‐3 replacing N‐6 4 1435 Risk Ratio (M‐H, Random, 95% CI) 0.69 [0.41, 1.19]
16.4 N‐3 replacing carbohydrates/sugars 1 281 Risk Ratio (M‐H, Random, 95% CI) 0.69 [0.12, 4.07]
16.5 N‐3 replacing nil/low n‐3 placebo 8 19275 Risk Ratio (M‐H, Random, 95% CI) 0.84 [0.73, 0.96]
16.6 Replacement unclear 2 3186 Risk Ratio (M‐H, Random, 95% CI) 0.54 [0.05, 5.77]
17 CVD mortality ‐ LCn3 ‐ subgroup by intervention type 25 67772 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.03]
17.1 Dietary advice 2 5147 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.52, 1.71]
17.2 Supplemental foods 2 5039 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.72, 1.32]
17.3 Supplements (capsule) 21 57586 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.88, 0.99]
17.4 Any combination 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
18 CVD mortality ‐ LCn3 ‐ subgroup by duration 25 67772 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.03]
18.1 Medium duration 1 to < 2 years in study 10 6177 Risk Ratio (M‐H, Random, 95% CI) 0.88 [0.57, 1.36]
18.2 Medium‐long duration: 2 to < 4 years in study 10 26736 Risk Ratio (M‐H, Random, 95% CI) 0.89 [0.82, 0.95]
18.3 Long duration: ≥ 4 years in study 5 34859 Risk Ratio (M‐H, Random, 95% CI) 1.05 [0.93, 1.18]
19 CVD mortality ‐ LCn3 ‐ subgroup by primary or secondary prevention 25 67772 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.03]
19.1 Primary prevention 7 17931 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.88, 1.09]
19.2 Secondary prevention 18 49841 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.83, 1.06]
20 CVD mortality ‐ LCn3 ‐ subgroup by statin uses 25 67772 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.03]
20.1 LCn3 ‐ ≥ 50% of control group on statins 6 23994 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.90, 1.10]
20.2 LCn3 ‐ < 50% of control group on statins 17 43425 Risk Ratio (M‐H, Random, 95% CI) 0.92 [0.82, 1.04]
20.3 LCn3‐ Use of statins unclear 2 353 Risk Ratio (M‐H, Random, 95% CI) 0.36 [0.06, 2.30]
21 Cardiovascular events (overall) ‐ LCn3 38 90378 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.94, 1.04]
22 CVD events ‐ LCn3 ‐ SA fixed‐effect 38 90378 Risk Ratio (M‐H, Fixed, 95% CI) 0.98 [0.95, 1.00]
23 CVD events ‐ LCn3 ‐ SA by summary risk of bias 38 90378 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.94, 1.04]
23.1 Low risk of bias 14 31649 Risk Ratio (M‐H, Random, 95% CI) 1.00 [0.96, 1.05]
23.2 Moderate/high risk of bias 24 58729 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.03]
24 CVD events ‐ LCn3 ‐ SA by compliance and study size 37 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
24.1 SA ‐ low risk of compliance bias 16 13649 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.84, 1.14]
24.2 SA ‐ 100+ randomised 33 90058 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.94, 1.04]
25 CVD events ‐ LCn3 ‐ subgroup by dose 38 90453 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.94, 1.04]
25.1 LCn3 ≤ 150 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
25.2 LCn3 > 150 ≤ 250 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
25.3 LCn3 > 250 ≤ 400 mg/d 1 2033 Risk Ratio (M‐H, Random, 95% CI) 0.96 [0.88, 1.05]
25.4 LCn3 > 400 ≤ 2400 mg/d 28 85818 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.93, 1.05]
25.5 LCn3 > 2.4 ≤ 4.4 g/d 7 2180 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.75, 1.28]
25.6 LCn3 > 4.4 g/d 3 422 Risk Ratio (M‐H, Random, 95% CI) 1.09 [0.65, 1.81]
26 CVD events ‐ LCn3 ‐ subgroup by replacement 38 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
26.1 N‐3 replacing SFA 4 2888 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.87, 1.04]
26.2 N‐3 replacing MUFA 16 45065 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.94, 1.02]
26.3 N‐3 replacing n‐6 6 1891 Risk Ratio (M‐H, Random, 95% CI) 1.10 [0.90, 1.35]
26.4 N‐3 replacing carbohydrates/sugars 1 258 Risk Ratio (M‐H, Random, 95% CI) 0.68 [0.12, 3.98]
26.5 N‐3 replacing nil/low n‐3 placebo 12 39907 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.85, 1.07]
26.6 Replacement unclear 3 3429 Risk Ratio (M‐H, Random, 95% CI) 0.58 [0.16, 2.07]
27 CVD events ‐ LCn3 ‐ subgroup by intervention type 38 90378 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.94, 1.04]
27.1 Dietary advice 3 5248 Risk Ratio (M‐H, Random, 95% CI) 1.13 [0.86, 1.49]
27.2 Supplemental foods 2 5039 Risk Ratio (M‐H, Random, 95% CI) 1.02 [0.89, 1.17]
27.3 Supplements (capsule) 33 80091 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.91, 1.02]
27.4 Any combination 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
28 CVD events ‐ LCn3 ‐ subgroup by duration 38 90378 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.94, 1.04]
28.1 Medium duration 1 to < 2 years in study 18 8107 Risk Ratio (M‐H, Random, 95% CI) 0.89 [0.68, 1.16]
28.2 Medium‐long duration: 2 to < 4 years in study 14 28767 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.93, 1.01]
28.3 Long duration: ≥ 4 years in study 6 53504 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.91, 1.08]
29 CVD events ‐ LCn3 ‐ subgroup by primary or secondary prevention 38 90378 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.94, 1.04]
29.1 Primary prevention of CVD 16 39751 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.89, 1.05]
29.2 Secondary prevention 22 50627 Risk Ratio (M‐H, Random, 95% CI) 1.00 [0.93, 1.07]
30 CVD events ‐ LCn3 ‐ subgroup by statin use 38 90378 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.94, 1.04]
30.1 LCn3 ‐ ≥ 50% of control group on statins 8 42389 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.89, 1.08]
30.2 LCn3 ‐ < 50% of control group on statins 24 45160 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.91, 1.04]
30.3 LCn3 ‐ use of statins unclear 6 2829 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.53, 1.63]
31 Coronary heart disease mortality (overall) ‐ LCn3 21 73491 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.09]
32 CHD mortality ‐ LCn3 ‐ SA fixed‐effect 21 73491 Risk Ratio (M‐H, Fixed, 95% CI) 0.94 [0.85, 1.03]
33 CHD mortality ‐ LCn3 ‐ SA by summary risk of bias 21 73491 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.09]
33.1 Low risk of bias 7 16372 Risk Ratio (M‐H, Random, 95% CI) 1.00 [0.72, 1.37]
33.2 Moderate/high risk of bias 14 57119 Risk Ratio (M‐H, Random, 95% CI) 0.91 [0.75, 1.10]
34 CHD mortality ‐ LCn3 ‐ SA by compliance and study size 21 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
34.1 SA ‐ low risk of compliance bias 9 12938 Risk Ratio (M‐H, Random, 95% CI) 1.05 [0.83, 1.32]
34.2 SA ‐ 100+ randomised 20 73411 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.09]
35 CHD mortality ‐ LCn3 ‐ SA omitting cardiac death 16 65325 Risk Ratio (M‐H, Random, 95% CI) 0.83 [0.74, 0.94]
35.1 Low risk of bias 5 12022 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.69, 1.30]
35.2 Moderate/high risk of bias 11 53303 Risk Ratio (M‐H, Random, 95% CI) 0.82 [0.72, 0.94]
36 CHD mortality ‐ LCn3 ‐ subgroup by dose 21 73491 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.09]
36.1 LCn3 ≤ 150 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
36.2 LCn3 > 150 ≤ 250 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
36.3 LCn3 > 250 ≤ 400 mg/d 2 5147 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.50, 1.74]
36.4 LCn3 > 400 ≤ 2400 mg/d 15 67442 Risk Ratio (M‐H, Random, 95% CI) 0.92 [0.80, 1.07]
36.5 LCn3 > 2.4 ≤ 4.4 g/d 3 822 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.49, 1.78]
36.6 LCn3 > 4.4 g/d 1 80 Risk Ratio (M‐H, Random, 95% CI) 0.32 [0.01, 7.57]
37 CHD mortality ‐ LCn3 ‐ subgroup by replacement 21 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
37.1 N‐3 replacing SFA 3 2514 Risk Ratio (M‐H, Random, 95% CI) 0.67 [0.51, 0.88]
37.2 N‐3 replacing MUFA 10 31605 Risk Ratio (M‐H, Random, 95% CI) 0.89 [0.72, 1.10]
37.3 N‐3 replacing n‐6 3 1409 Risk Ratio (M‐H, Random, 95% CI) 0.64 [0.33, 1.24]
37.4 N‐3 replacing carbohydrates/sugars 1 258 Risk Ratio (M‐H, Random, 95% CI) 0.34 [0.01, 8.23]
37.5 N‐3 replacing nil/low n‐3 placebo 7 37651 Risk Ratio (M‐H, Random, 95% CI) 0.83 [0.70, 0.97]
37.6 Replacement unclear 1 3114 Risk Ratio (M‐H, Random, 95% CI) 1.27 [1.03, 1.57]
38 CHD mortality ‐ LCn3 ‐ subgroup by intervention type 21 73491 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.09]
38.1 Dietary advice 2 5147 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.50, 1.74]
38.2 Supplemental foods 1 4837 Risk Ratio (M‐H, Random, 95% CI) 0.96 [0.69, 1.33]
38.3 Supplements (capsule) 18 63507 Risk Ratio (M‐H, Random, 95% CI) 0.90 [0.79, 1.02]
38.4 Any combination 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
39 CHD mortality ‐ LCn3 ‐ subgroup by duration 21 73491 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.09]
39.1 Medium duration 1 to < 2 years in study 7 5978 Risk Ratio (M‐H, Random, 95% CI) 0.96 [0.62, 1.50]
39.2 Medium‐long duration: 2 to < 4 years in study 9 26545 Risk Ratio (M‐H, Random, 95% CI) 0.79 [0.69, 0.90]
39.3 Long duration: ≥ 4 years in study 5 40968 Risk Ratio (M‐H, Random, 95% CI) 1.18 [1.00, 1.39]
40 CHD mortality ‐ LCn3 ‐ subgroup by primary or secondary prevention 21 73491 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.09]
40.1 Primary prevention of CVD 5 23789 Risk Ratio (M‐H, Random, 95% CI) 0.86 [0.46, 1.61]
40.2 Secondary prevention of CVD 16 49702 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.11]
41 CHD mortality ‐ LCn3 ‐ subgroup by statin use 21 73491 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.79, 1.09]
41.1 LCn3 ‐ ≥ 50% of control group on statins 5 30025 Risk Ratio (M‐H, Random, 95% CI) 1.05 [0.84, 1.30]
41.2 LCn3 ‐ < 50% of control group on statins 15 43208 Risk Ratio (M‐H, Random, 95% CI) 0.89 [0.72, 1.10]
41.3 LCn3 ‐ use of statins unclear 1 258 Risk Ratio (M‐H, Random, 95% CI) 0.34 [0.01, 8.23]
42 CHD mortality ‐ LCn3 ‐ subgroup by CAD history 21 73491 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.80, 1.09]
42.1 Previous CAD 11 29074 Risk Ratio (M‐H, Random, 95% CI) 0.96 [0.77, 1.20]
42.2 No previous CAD 10 44417 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.74, 1.16]
43 Coronary heart disease events (overall) ‐ LCn3 28 84301 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.88, 0.97]
44 CHD events ‐ LCn3 ‐ SA fixed‐effect 28 84301 Risk Ratio (M‐H, Fixed, 95% CI) 0.93 [0.88, 0.97]
45 CHD events ‐ LCn3 ‐ SA by summary risk of bias 28 84301 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.88, 0.97]
45.1 Low risk of bias 12 30227 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.90, 1.05]
45.2 Moderate/high risk of bias 16 54074 Risk Ratio (M‐H, Random, 95% CI) 0.89 [0.84, 0.95]
46 CHD events ‐ LCn3 ‐ SA by compliance and study size 27 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
46.1 SA ‐ low risk of compliance bias 12 13447 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.86, 1.02]
46.2 SA ‐ 100+ randomised 25 84084 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.88, 0.98]
47 CHD events ‐ LCn3 ‐ subgroup by dose 28 84376 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.89, 0.98]
47.1 LCn3 ≤ 150 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
47.2 LCn3 > 150 ≤ 250 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
47.3 LCn3 > 250 ≤ 400 mg/d 1 2033 Risk Ratio (M‐H, Random, 95% CI) 0.92 [0.82, 1.04]
47.4 LCn3 > 400 ≤ 2400 mg/d 21 80730 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.88, 0.98]
47.5 LCn3 > 2.4 ≤ 4.4 g/d 4 1191 Risk Ratio (M‐H, Random, 95% CI) 0.90 [0.53, 1.53]
47.6 LCn3 > 4.4 g/d 3 422 Risk Ratio (M‐H, Random, 95% CI) 1.00 [0.54, 1.85]
48 CHD events ‐ LCn3 ‐ subgroup by replacement 28 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
48.1 N‐3 replacing SFA 3 2514 Risk Ratio (M‐H, Random, 95% CI) 0.53 [0.16, 1.75]
48.2 N‐3 replacing MUFA 15 44954 Risk Ratio (M‐H, Random, 95% CI) 0.96 [0.90, 1.01]
48.3 N‐3 replacing n‐6 4 1549 Risk Ratio (M‐H, Random, 95% CI) 1.10 [0.88, 1.39]
48.4 N‐3 replacing carbohydrates/sugars 1 258 Risk Ratio (M‐H, Random, 95% CI) 0.11 [0.01, 2.07]
48.5 N‐3 replacing nil/low n‐3 placebo 8 37843 Risk Ratio (M‐H, Random, 95% CI) 0.85 [0.78, 0.94]
48.6 Replacement unclear 1 243 Risk Ratio (M‐H, Random, 95% CI) 0.89 [0.08, 9.70]
49 CHD events ‐ LCn3 ‐ subgroup by intervention type 28 84301 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.89, 0.98]
49.1 Dietary advice 2 2134 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.67, 1.52]
49.2 Supplemental foods 2 5039 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.75, 1.18]
49.3 Supplements (capsule) 24 77128 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.88, 0.98]
49.4 Any combination 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
50 CHD events ‐ LCn3 ‐ subgroup by duration 28 84301 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.89, 0.98]
50.1 Medium duration 1 to < 2 years in study 11 7009 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.86, 1.03]
50.2 Medium‐long duration: 2 to < 4 years in study 12 26902 Risk Ratio (M‐H, Random, 95% CI) 0.91 [0.84, 0.98]
50.3 Long duration: ≥ 4 years in study 5 50390 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.83, 1.07]
51 CHD events ‐ LCn3 ‐ subgroup by primary or secondary prevention 28 84301 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.89, 0.98]
51.1 Primary prevention of CVD 11 37365 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.81, 1.10]
51.2 Secondary prevention of CVD 17 46936 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.88, 0.98]
52 CHD events ‐ LCn3 ‐ subgroup by statin use 28 84301 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.89, 0.98]
52.1 LCn3 ‐ ≥ 50% of control group on statins 8 42735 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.85, 1.05]
52.2 LCn3 ‐ < 50% of control group on statins 17 40674 Risk Ratio (M‐H, Random, 95% CI) 0.92 [0.86, 0.98]
52.3 LCn3 ‐ use of statins unclear 3 892 Risk Ratio (M‐H, Random, 95% CI) 0.65 [0.11, 3.83]
53 CHD events ‐ LCn3 subgroup by CAD history 28 84301 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.88, 0.97]
53.1 Previous CAD 12 26124 Risk Ratio (M‐H, Random, 95% CI) 0.92 [0.87, 0.98]
53.2 No previous CAD 16 58177 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.86, 1.01]
54 Stroke (overall) ‐ LCn3 28 89358 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.96, 1.16]
55 Stroke ‐ LCn3 ‐ SA fixed‐effect 28 89358 Risk Ratio (M‐H, Fixed, 95% CI) 1.06 [0.97, 1.16]
56 Stroke ‐ LCn3 ‐ SA by summary risk of bias 28 89358 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.96, 1.16]
56.1 Low risk of bias 12 32039 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.86, 1.12]
56.2 Moderate/high risk of bias 16 57319 Risk Ratio (M‐H, Random, 95% CI) 1.13 [1.00, 1.29]
57 Stroke ‐ LCn3 ‐ SA by compliance and study size 27 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
57.1 SA ‐ low risk of compliance bias 12 14451 Risk Ratio (M‐H, Random, 95% CI) 1.19 [0.86, 1.65]
57.2 SA ‐ 100+ randomised 26 89231 Risk Ratio (M‐H, Random, 95% CI) 1.07 [0.97, 1.18]
58 Stroke ‐ LCn3 ‐ subgroup by stroke type 13 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
58.1 Ischaemic stroke ‐ LCn3 8 35040 Risk Ratio (M‐H, Random, 95% CI) 1.09 [0.89, 1.33]
58.2 Haemorrhagic stroke ‐ LCn3 8 36645 Risk Ratio (M‐H, Random, 95% CI) 1.20 [0.85, 1.69]
58.3 Transient ischaemic attack (TIA) 5 5032 Risk Ratio (M‐H, Random, 95% CI) 0.74 [0.39, 1.39]
59 Stroke ‐ LCn3 ‐ subgroup by dose 28 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
59.1 LCn3 ≤ 150 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
59.2 LCn3 > 150 ≤ 250 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
59.3 LCn3 > 250 ≤ 400 mg/d 1 2033 Risk Ratio (M‐H, Random, 95% CI) 0.45 [0.14, 1.44]
59.4 LCn3 > 400 ≤ 2400 mg/d 24 86335 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.97, 1.16]
59.5 LCn3 > 2.4 ≤ 4.4 g/d 1 610 Risk Ratio (M‐H, Random, 95% CI) 0.69 [0.16, 3.07]
59.6 LCn3 > 4.4 g/d 2 380 Risk Ratio (M‐H, Random, 95% CI) 6.58 [0.78, 55.16]
60 Stroke ‐ LCn3 ‐ subgroup by replacement 28 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
60.1 N‐3 replacing SFA 3 2514 Risk Ratio (M‐H, Random, 95% CI) 0.53 [0.19, 1.50]
60.2 N‐3 replacing MUFA 14 45252 Risk Ratio (M‐H, Random, 95% CI) 1.11 [0.94, 1.31]
60.3 N‐3 replacing n‐6 3 1179 Risk Ratio (M‐H, Random, 95% CI) 2.08 [0.18, 24.31]
60.4 N‐3 replacing carbohydrates/sugars 1 258 Risk Ratio (M‐H, Random, 95% CI) 0.34 [0.01, 8.23]
60.5 N‐3 replacing nil/low n‐3 placebo 9 39555 Risk Ratio (M‐H, Random, 95% CI) 1.07 [0.92, 1.24]
60.6 Replacement unclear 1 3114 Risk Ratio (M‐H, Random, 95% CI) 1.12 [0.55, 2.29]
61 Stroke ‐ LCn3 ‐ subgroup by intervention type 28 89358 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.96, 1.16]
61.1 Dietary advice 3 5248 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.42, 2.05]
61.2 Supplemental foods 1 4837 Risk Ratio (M‐H, Random, 95% CI) 1.11 [0.47, 2.62]
61.3 Supplements (capsule) 24 79273 Risk Ratio (M‐H, Random, 95% CI) 1.07 [0.97, 1.18]
61.4 Any combination 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
62 Stroke ‐ LCn3 ‐ subgroup by duration 28 89358 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.96, 1.16]
62.1 Medium duration 1 to < 2 years in study 11 7467 Risk Ratio (M‐H, Random, 95% CI) 1.35 [0.86, 2.12]
62.2 Medium‐long duration: 2 to < 4 years in study 11 28387 Risk Ratio (M‐H, Random, 95% CI) 1.15 [0.93, 1.41]
62.3 Long duration: ≥ 4 years in study 6 53504 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.91, 1.13]
63 Stroke ‐ LCn3 ‐ subgroup by primary or secondary prevention 28 89358 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.96, 1.16]
63.1 Primary prevention of CVD 9 39332 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.86, 1.09]
63.2 Secondary prevention of CVD 19 50026 Risk Ratio (M‐H, Random, 95% CI) 1.21 [1.05, 1.40]
64 Stroke ‐ LCn3 ‐ subgroup by statin use 28 89358 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.96, 1.16]
64.1 LCn3 ‐ ≥ 50% of control group on statins 8 42962 Risk Ratio (M‐H, Random, 95% CI) 1.03 [0.86, 1.23]
64.2 LCn3 ‐ < 50% of control group on statins 17 44999 Risk Ratio (M‐H, Random, 95% CI) 1.18 [1.02, 1.37]
64.3 LCn3 ‐ use of statins unclear 3 1397 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.38, 2.34]
65 Arrythmia (overall) ‐ LCn3 27 53796 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.90, 1.05]
66 Arrhythmia‐ LCn3 ‐ SA fixed‐effect 27 53796 Risk Ratio (M‐H, Fixed, 95% CI) 1.01 [0.96, 1.07]
67 Arrhythmia‐ LCn3 ‐ SA by summary risk of bias 27 53796 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.90, 1.05]
67.1 Low risk of bias 10 25801 Risk Ratio (M‐H, Random, 95% CI) 1.10 [0.98, 1.23]
67.2 Moderate/high risk of bias 17 27995 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.84, 1.02]
68 Arrhythmia‐ LCn3 ‐ SA by compliance and study size 26 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
68.1 SA ‐ low risk of compliance bias 10 12914 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.86, 1.09]
68.2 SA ‐ 100+ randomised 26 53749 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.89, 1.05]
69 Arrhythmia ‐ LCn3 ‐ subgroup by new or recurrent 27 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
69.1 New arrhythmia 16 50175 Risk Ratio (M‐H, Random, 95% CI) 1.07 [0.99, 1.16]
69.2 Recurrent arrhythmia 12 4425 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.84, 1.03]
70 Arrhythmia ‐ LCn3 ‐ subgroup by fatality 17 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
70.1 Fatal arrhythmias ‐ LCn3 2 12938 Risk Ratio (M‐H, Random, 95% CI) 1.11 [0.95, 1.31]
70.2 Non‐fatal arrhythmias ‐ LCn3 8 2079 Risk Ratio (M‐H, Random, 95% CI) 0.74 [0.57, 0.96]
70.3 Fatal and non‐fatal arrhythmias combined ‐ LCn3 10 36007 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.97, 1.17]
71 Arrhythmia ‐ LCn3 ‐ subgroup by dose 27 53796 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.89, 1.04]
71.1 LCn3 ≤ 150 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
71.2 LCn3 > 150 ≤ 250 mg/d 1 407 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.90, 1.12]
71.3 LCn3 > 250 ≤ 400 mg/d 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
71.4 LCn3 > 400 ≤ 2400 mg/d 19 51535 Risk Ratio (M‐H, Random, 95% CI) 0.98 [0.88, 1.08]
71.5 LCn3 > 2.4 ≤ 4.4 g/d 3 1076 Risk Ratio (M‐H, Random, 95% CI) 0.72 [0.55, 0.94]
71.6 LCn3 > 4.4 g/d 2 342 Risk Ratio (M‐H, Random, 95% CI) 1.10 [0.32, 3.83]
71.7 Unclear LCn3 dose 2 436 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.76, 1.28]
72 Arrhythmia ‐ LCn3 ‐ subgroup by replacement 27 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
72.1 N‐3 replacing SFA 2 632 Risk Ratio (M‐H, Random, 95% CI) 0.74 [0.10, 5.67]
72.2 N‐3 replacing MUFA 12 42246 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.88, 1.11]
72.3 N‐3 replacing n‐6 4 1302 Risk Ratio (M‐H, Random, 95% CI) 1.00 [0.86, 1.16]
72.4 N‐3 replacing carbohydrates/sugars 1 258 Risk Ratio (M‐H, Random, 95% CI) 0.34 [0.04, 3.21]
72.5 N‐3 replacing nil/low n‐3 placebo 6 8983 Risk Ratio (M‐H, Random, 95% CI) 0.80 [0.69, 0.91]
72.6 Replacement unclear 4 1179 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.91, 1.08]
73 Arrhythmia ‐ LCn3 ‐ subgroup by intervention type 27 53796 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.90, 1.05]
73.1 Dietary advice 2 508 Risk Ratio (M‐H, Random, 95% CI) 0.87 [0.44, 1.72]
73.2 Supplemental foods 2 5039 Risk Ratio (M‐H, Random, 95% CI) 0.92 [0.67, 1.26]
73.3 Supplements (capsule) 23 48249 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.88, 1.06]
73.4 Any combination 0 0 Risk Ratio (M‐H, Random, 95% CI) 0.0 [0.0, 0.0]
74 Arrhythmia ‐ LCn3 ‐ subgroup by duration 27 53796 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.89, 1.04]
74.1 Medium duration 1 to < 2 years in study 17 8553 Risk Ratio (M‐H, Random, 95% CI) 0.93 [0.84, 1.04]
74.2 Medium‐long duration: 2 to < 4 years in study 7 17701 Risk Ratio (M‐H, Random, 95% CI) 0.96 [0.84, 1.10]
74.3 Long duration: ≥ 4 years in study 3 27542 Risk Ratio (M‐H, Random, 95% CI) 1.13 [0.99, 1.29]
75 Arrhythmia ‐ LCn3 ‐ subgroup by primary or secondary prevention3 27 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
75.1 Primary prevention 8 14565 Risk Ratio (M‐H, Random, 95% CI) 1.11 [0.97, 1.28]
75.2 Secondary prevention 19 39231 Risk Ratio (M‐H, Random, 95% CI) 0.95 [0.86, 1.03]
76 Arrhythmia ‐ LCn3 ‐ subgroup by statin use 27 Risk Ratio (M‐H, Random, 95% CI) Subtotals only
76.1 LCn3 ‐ ≥ 50% of control group on statins 5 23779 Risk Ratio (M‐H, Random, 95% CI) 1.07 [0.95, 1.22]
76.2 LCn3 ‐ < 50% of control group on statins 18 28932 Risk Ratio (M‐H, Random, 95% CI) 0.94 [0.85, 1.04]
76.3 LCn3 ‐ use of statins unclear 4 1085 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.80, 1.18]