The impact of omega-3 polyunsaturated fatty acid supplementation on the incidence of cardiovascular events and complications in peripheral arterial disease: a systematic review and meta-analysis

Five randomized, single-center trials (n=396) in adults aged roughly 64–66 years with established peripheral arterial disease (intermittent claudication; ABI ≤0.9); sex distribution not reported. Follow-up ranged from 16 weeks to 5 years; some participants had hyperlipidemia on statins or prior cardiovascular events; co-interventions varied.

Omega-3 PUFA regimens included EPA- and/or DHA-containing capsules (in one trial EPA 1.8 g/day + DHA 1.2 g/day; in another EPA 0.18–0.27 g/day) and, in a separate arm, a fortified dairy product delivering EPA, DHA and ALA. Daily durations ranged from 16 weeks to 5 years. Co-interventions included gamma-linolenic acid or vitamins B6 and E, folate and oleic acid; one trial had background statin therapy.

Omega-3 PUFA supplementation did not reduce major adverse cardiac events or other serious outcomes in PAD. Pooled MACE RR 0.73 (95% CI 0.22–2.41; I2=75%; 2 trials, 288 participants). No significant effects on myocardial infarction (Peto OR 0.64, 95% CI 0.22–1.88), cardiovascular death (Peto OR 0.60, 95% CI 0.19–1.90) or revascularization (RR 0.81, 95% CI 0.13–4.91). Pain-free walking distance showed no significant improvement (MD 115.40 m, 95% CI −42.24 to 273.05; I2=89%). GI upset was more frequent with EPA in one trial (RR 1.58, 95% CI 1.01–2.48). Exploratory subgroup analyses suggested longer treatment (≥6 months) at low dose may improve PFWD, but requires confirmation. Conclusion: There is insufficient evidence to support a beneficial effect of omega-3 PUFA supplementation on major cardiovascular events, revascularization or amputation, pain-free walking, or quality of life in PAD; more robust trials are needed.

Small number of trials (n=5) with 396 participants; unclear/high risk of bias across trials; substantial heterogeneity (I2=75%) in MACE; variability in omega-3 formulations, doses, durations, and co-interventions; adverse events incompletely reported; follow-up duration varied; potential sponsor influence in some trials.