Icosapent ethyl and gastrointestinal bleeds

Letter

I was pleased to read Australian Prescriber’s new drug review for icosapent ethyl,¹ which I know will provide Australian clinicians with a succinct overview to guide them in their clinical practice. However, a statement within the piece could be misinterpreted by your readers. Within the paragraph on adverse events, it is stated that ‘Bleeding, particularly from the gut, affected 11.8% of the patients taking icosapent ethyl (placebo 9.9%).’¹ To clarify, the majority of bleeding events in the icosapent ethyl–treated group were categorised as ‘other bleeds’ (9.2% patients), with only 3.1% of patients experiencing a gastrointestinal bleeding event; the corresponding incidence with placebo was 2.8%.² The rates of serious bleeding events (2.7% for icosapent ethyl and 2.1% for placebo) were driven by gastrointestinal bleeding (1.5% for icosapent ethyl and 1.1% for placebo).^2,3

Stephanie Ternel
Medical Lead, CSL Seqirus, Melbourne

Conflicts of interest: Stephanie Ternel is employed by CSL Seqirus which is the sponsor for isocapent ethyl (Vazkepa) in Australia.

 

References

1. Icosapent ethyl for reduction in cardiovascular disease risk in adults with hypertriglyceridaemia. Australian Prescriber 2024;47:197-8.
2. Therapeutic Goods Administration. Australian Public Assessment Report for Vazkepa. Department of Health and Aged Care; 2023. [cited 2025 Mar 17]
3. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019;380:11-22.

 

Editor’s comments:

Thank you for your feedback. Bleeding-related events were prespecified as adverse events of special interest in the evaluation of icosapent ethyl.¹ This is because icosapent ethyl is an ester of eicosapentaenoic acid, an omega-3 fatty acid found in fish oil, and omega-3 marine oil has been linked with an increase in bleeding time.¹ In the REDUCE-IT trial,² as Ternel points out, a majority of the bleeding events were classified as ‘other bleeds’ (defined as not involving the gastrointestinal tract or central nervous system). Gastrointestinal bleeding was, however, the most frequent individual type of bleed, and the most frequent type of serious bleed reported in the trial.^1,2

A recent meta-analysis of randomised trials reported increased risk of any bleeding event with icosapent ethyl compared with control (risk ratio 1.50, 95% confidence interval [CI] 1.13 to 1.99), although the absolute risk was low (0.6%, 95% CI 0.1 to 1.0%).³ The risk of gastrointestinal bleeding with icosapent ethyl was not individually reported in the meta-analysis.³

 

References 2

1. Therapeutic Goods Administration. Australian Public Assessment Report for Vazkepa. Department of Health and Aged Care; 2023. [cited 2025 Mar 17]
2. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019;380:11-22.
3. Javaid M, Kadhim K, Bawamia B, Cartlidge T, Farag M, Alkhalil M. Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Am Heart Assoc 2024;13:e032390.

 

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