Background
Methods
Data sources and searches
1. | (omega 3 fatty acid OR omega-3 fatty acid OR n 3 fatty acid OR n-3 fatty acid OR n-3 polyunsaturated fatty acid) |
2. | (dietary supplement OR dietary supplementation OR dietary fat) |
3. | (flax OR flaxseed OR flaxseed oil OR linseed oil) |
4. | (fish OR fish oil OR fatty fish OR marine) |
5. | (canola OR canola oil OR rapeseed oil) |
6. | (dietary supplements[MeSH Terms]) OR (dietary fats[MeSH Terms]) OR (flax[MeSH Terms]) OR (linseed oil[MeSH Terms]) OR (fishes[MeSH Terms]) OR (fish oils[MeSH Terms]) |
7. | (eicosapentaenoic acid OR EPA) |
8. | (docosahexaenoic acids OR DHA) |
9. | (alpha-linolenic acid OR ALA) |
10. | (fatty acids, omega-3[MeSH Terms]) OR (eicosapentaenoic acid[MeSH Terms]) OR (docosahexaenoic acids[MeSH Terms]) OR (alpha-linolenic acid[MeSH Terms]) |
11. | #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 |
12. | (peripheral arterial disease OR peripheral artery disease OR peripheral arterial diseases OR peripheral artery diseases) |
13. | (peripheral vascular disease OR peripheral vascular diseases OR peripheral angiopathy OR peripheral angiopathies) |
14. | (ankle brachial index OR ankle-brachial index OR ankle brachial indices OR ankle-brachial indices OR intermittent claudication) |
15. | (peripheral arterial disease[MeSH Terms]) OR (peripheral vascular diseases[MeSH Terms]) OR (ankle-brachial index[MeSH Terms]) OR (intermittent claudication[MeSH Terms]) |
16. | #12 OR #13 OR #14 OR #15 |
17. | (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab]) NOT (animals[mh] NOT humans[mh]) |
18. | #11 AND #16 AND #17 |
Study selection
Data extraction and quality assessment
Data synthesis and analysis
Results
Characteristics of trial populations and interventions
Study | Population | Intervention | |||||||
---|---|---|---|---|---|---|---|---|---|
Age (years) | BMI (kg/m2) | Diagnosis of PAD | Medication/therapy | Co-morbidities | Omega-3 PUFA (g/day) | Comparator (g/day) | Co-intervention | Duration | |
Gans 1990 [37] | 66.1 ± 8.2 | NR | Treadmill testing for IC classification; IC stable for ≥ 1 yr | Excluded patients on lipid-lowering or platelet-active drugs | None reported | EPA (1.8) + DHA (1.2) | Corn oil (3.0) | None | 16 wk |
Leng 1998 [34] | 65.7 ± 7.1 | 26.7 ± 4.2 | Edinburgh Claudication Questionnaire; IC stable for ≥ 6 mth; ABI < 0.9 | Included patients taking aspirin | Excluded patients with critical ischemia, previous or impending surgery, unstable angina or MI, or severe concurrent illnesses | EPA (0.18-0.27) | Sunflower oil (2.0 – 3.0) | Gamma-linolenic acid | 2 yr |
Carrero 2005 [35] | 64.0 ± 9.0 | 27.9 ± 3.9 | Presence of IC; ABI < 0.7 | Excluded patients eligible for vascular surgery; excluded patients taking statins | Excluded patients with history of cardiac events or with endocrine or metabolic disturbances. Included patients who were smokers, had T2D or hypertension | EPA (0.2) + DHA (0.13) + ALA (0.06) | Placebo (dairy product) | Vitamins B6 and E, folate, oleic acid | 1 yr |
Carrero 2006 [36] | 65.5 ± 9.5 | 27.7 ± 3.4 | Presence of IC; ABI < 0.7 | Excluded patients eligible for vascular surgery; excluded patients taking statins | Excluded patients with history of cardiac events or with endocrine or metabolic disturbances. Included patients who were smokers, had T2D or hypertension | EPA (0.2) + DHA (0.13) + ALA (0.06) | Placebo (dairy product) | Vitamins B6 and E, folate, oleic acid | 1 yr |
Ishikawa 2010 [38] | 65.2 ± 7.4 | 23.3 ± 2.8 | Presence of IC; physical findings (e.g. ulcer) and ABI | All patients included were taking statins | Hyperlipidemia (total serum cholesterol) | EPA (1.8) | No treatment | Simvastatin or Pravastatin | up to 5 yr |
Study | Selection bias | Performance bias | Attrition bias | Reporting bias | Other sources of bias | Overall risk of bias | |
---|---|---|---|---|---|---|---|
Random sequence generation | Allocation concealment | Blinding of participants and personnel | Incomplete outcome data | Selective reporting | |||
Gans 1990 [37] | Low risk | Low risk | Unclear risk | Unclear risk | Unclear risk | Low risk |
Unclear risk
|
Leng 1998 [34] | Low risk | Low risk | Low risk | High risk¶
| Unclear risk | Unclear risk* |
High risk
|
Carrero 2005 [35] | Low risk | Unclear risk | Low risk | Unclear risk | Unclear risk | High risk§
|
High risk
|
Carrero 2006 [36] | Low risk | Unclear risk | Low risk | Unclear risk | Unclear risk | High risk§
|
High risk
|
Ishikawa 2010 [38] | Low risk | Unclear risk | Unclear risk | Unclear risk | Unclear risk | Low risk |
Unclear risk
|
Risk of bias in included trials
Major adverse cardiac events
Secondary clinical outcomes
Outcome | No. of trials | No. of events/total patients in cohort | Effect estimate (95% CI) |
I
2
| |
---|---|---|---|---|---|
Omega-3 PUFA | Control | ||||
2 | 6/156 | 8/132 | Peto OR, 0.64 (0.22, 1.88) | 0% | |
2 | 5/156 | 7/132 | Peto OR, 0.60 (0.19, 1.90) | 0% | |
Stroke (Leng 1998 [34]) | 1 | 3/60 | 1/60 | Peto OR, 2.79 (0.38, 20.31) | NE |
Angina (Ishikawa 2010 [38]) | 1 | 5/117 | 8/106 | RR, 0.57 (0.19, 1.68) | NE |
Adverse Effects | |||||
2 | 17/76 | 21/76 | RR 0.81 (0.48, 1.38) | NE | |
Gastrointestinal Upset (Leng 1998 [34]) | 1 | 30/60 | 19/60 | RR 1.58 (1.01, 2.48) | NE |
2 | 9/156 | 13/132 | RR, 0.81 (0.13, 4.91) | 59% | |
Amputation (Leng 1998 [34]) | 1 | 0/60 | 1/60 | Peto OR, 0.14 (0.00, 6.82) | NE |
4 | 95 | 88 | MD, 115.40 (-42.24, 273.05) | 89% | |
Maximum Walking Distance (Gans 1990 [37]) | 1 | 16 | 16 | MD, -26.00 (-71.92, 19.92) | NE |
Subgroup analyses
Subgroup | No. of trials | Total patients in cohort | Effect estimate (95% CI) |
I
2
| |
---|---|---|---|---|---|
Omega-3 PUFA | Control | ||||
Effect of Intervention Duration on PFWD
| |||||
Less than 6 months (Gans 1990 [37]) | 1 | 16 | 16 | MD, -31.00 (-74.34, 12.34) | NE |
3 | 79 | 72 | MD, 172.98 (-0.82, 346.77) | 80% | |
Effect of Omega-3 PUFA Dose on PFWD
| |||||
More than 0.3 g/day (Gans 1990 [37]) | 1 | 16 | 16 | MD, -31.00 (-74.34, 12.34) | NE |
3 | 79 | 72 | MD, 172.98 (-0.82, 346.77) | 80% | |
Effect of Omega-3 PUFA Type on PFWD
| |||||
2 | 40 | 36 | MD, 260.33 (160.05, 360.60) | 0% | |
EPA + DHA (Gans 1990 [37]) | 1 | 16 | 16 | MD, -31.00 (-74.34, 12.34) | NE |
EPA (Leng 1998 [34]) | 1 | 39 | 36 | MD, 10.00 (-109.07, 129.07) | NE |