Abstract

Background: Benefits of omega-3 administration in preventing cardiovascular (CV) events are controversial. In particular, while statins have been associated with significant reduction of revascularizations (Revasc), effects of omega-3 on Revasc are unclear. Aim: To metanalyze evidence on the effect of omega-3 administration on incident Revasc and CV events (myocardial infarction [MI], stroke, heart failure [HF], CV death). Methods: We searched MEDLINE, Embase, Scopus, Web-of-Science and Cochrane Library for randomized controlled trials (RCTs) with ≥500 participants comparing the effects of omega-3 formulations [decosahexanoic acid+eicosapentaenoic acid (DHA+EPA) or EPA alone] versus placebo. Results: Seventeen RCTs with participants (both primary and secondary CV prevention) randomized to DHA+EPA (n=52,498) or EPA alone (n=13,415) and controls (n=65,771) were included. Follow-up ranged from 4.5 months to 7.4 years. Significant heterogeneity emerged among studies (Figure). Overall, compared to controls omega-3 supplementation was associated with reduced risk of Revasc (Figure) and MI [0.89, 95% CI 0.80-0.98; p heter =0.04; I 2 =45%; p=0.02] with no significant effect on stroke, HF, and CV death. Reduced risk of Revasc was still observed when most (≥60%) participants were already on statins (Figure). Compared to DHA+EPA, EPA alone was associated with a greater reduced risk of Revasc (Figure) and stroke [0.72, 95% CI 0.55-0.95], with no significant effect on HF and CV death. No significant differences were observed for DHA+EPA dose ≤0.9g/day vs >0.9g/day, or EPA alone ≤0.7 g/day vs >0.7 g/day. Conclusions: Omega-3 supplementation resulted in reduced risk of Revascularization, unaffected by background statin use. Use of EPA alone appeared to be associated with even greater benefits. Further studies are needed to clarify the role of omega-3 supplementation in preventing hard CV events

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