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Meta-Analysis
. 2024 May 21;13(10):e032390.
doi: 10.1161/JAHA.123.032390. Epub 2024 May 14.

Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Mustafa Javaid  1 , Kadhim Kadhim  1 , Bilal Bawamia  1 , Timothy Cartlidge  1 , Mohamed Farag  1 , Mohammad Alkhalil  1   2
Affiliations
Meta-Analysis

Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Mustafa Javaid et al. J Am Heart Assoc. .

Abstract

Background: There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega-3 PUFAs or the background use of antiplatelet treatment.

Methods and results: Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega-3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta-analytic events of bleeding among patients receiving omega-3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91-1.31]; P=0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high-dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05-0.43]; P=0.02) but not the background use of antiplatelet therapy (risk difference, -0.01 [95% CI, -0.02 to 0]; P=0.056).

Conclusions: Omega-3 PUFAs were not associated with increased bleeding risk. Patients receiving high-dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.

Keywords: antiplatelet; bleeding; meta‐analysis; polyunsaturated fatty acids.

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Figures

Figure 1
Figure 1. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram of the selected studies.
Figure 2
Figure 2. Meta‐analysis of any bleeding events of included studies.
Individual and pooled rate ratio and 95% CIs of patients receiving omega‐3 polyunsaturated fatty acids (PUFAs) vs control.
Figure 3
Figure 3. Meta‐analysis of hemorrhagic stroke (top panel) and intracranial bleed (bottom panel) of the included studies.
Individual and pooled rate ratio and 95% CIs of patients receiving omega‐3 polyunsaturated fatty acids (PUFAs) vs control.
Figure 4
Figure 4. Meta‐regression of difference in bleeding risk, eicosapentaenoic acid (EPA) dose, and background use of antiplatelet therapy.
Left panel illustrates the significant relationship between the dose of EPA and increased bleeding risk among the included studies (the size of the bubble reflects the sample size of the study). The risk difference was calculated per 1‐gram increase in EPA dose. Right panel demonstrates the negative and nonsignificant association between the proportion of patients receiving antiplatelet treatment and the difference in bleeding in patients receiving omega‐3 PUFAs and control.
See this image and copyright information in PMC

References

    1. Castaner O, Pinto X, Subirana I, Amor AJ, Ros E, Hernaez A, Martinez‐Gonzalez MA, Corella D, Salas‐Salvado J, Estruch R, et al. Remnant cholesterol, not LDL cholesterol, is associated with incident cardiovascular disease. J Am Coll Cardiol. 2020;76:2712–2724. doi: 10.1016/j.jacc.2020.10.008 - DOI - PubMed
    1. Doi T, Langsted A, Nordestgaard BG. Elevated remnant cholesterol reclassifies risk of ischemic heart disease and myocardial infarction. J Am Coll Cardiol. 2022;79:2383–2397. doi: 10.1016/j.jacc.2022.03.384 - DOI - PMC - PubMed
    1. Ascherio A, Rimm EB, Stampfer MJ, Giovannucci EL, Willett WC. Dietary intake of marine n‐3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med. 1995;332:977–982. doi: 10.1056/NEJM199504133321501 - DOI - PubMed
    1. Phillipson BE, Rothrock DW, Connor WE, Harris WS, Illingworth DR. Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N Engl J Med. 1985;312:1210–1216. doi: 10.1056/NEJM198505093121902 - DOI - PubMed
    1. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11–22. doi: 10.1056/NEJMoa1812792 - DOI - PubMed

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