New from REDUCE-IT: icosapent ethyl treatment benefits total disease burden
January 2026
In this latest analysis, treatment with icosapent ethyl reduced hospitalizations and the duration of hospitalization for individuals at high cardiovascular risk, implying both clinical and patient-centred benefits.
Szarek M, Bhatt DL, Miller M, et al. Effects of icosapent ethyl on risk and duration of hospitalizations and death in REDUCE-IT. Eur J Prev Cardiol 2026: doi: 10.1093/eurjpc/zwag040.
STUDY SUMMARY
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Objective |
To investigate the effect of treatment with icosapent ethyl on total hospitalizations and days lost to hospitalization and death for high cardiovascular risk patients with elevated triglycerides in REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial).
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Study design |
REDUCE-IT was a randomized, double-blind, placebo-controlled study that included 8,179 statin-treated patients with elevated triglycerides and established or at high risk of cardiovascular disease. Eligible patients were randomized to treatment with 2 g twice daily of icosapent ethyl or matching placebo (1). This report describes a post hoc analysis of this trial.
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Study population |
The REDUCE-IT population was on statin therapy with established cardiovascular disease or age ≥50 years with diabetes and ≥1 additional risk factor, fasting triglycerides 1.69 – 5.63 mmol/L, and low-density lipoprotein cholesterol 1.06 – 2.59 mmol/L.
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Main study variables |
Total hospitalizations and days lost to hospitalizations.
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Methods |
Admissions to hospital or the emergency department after randomization were reported as either efficacy endpoints or adverse events. Efficacy endpoints (i.e. death due to cardiovascular, non-cardiovascular, or undetermined causes, myocardial infarction, coronary revascularization, cardiac arrhythmia, unstable angina, congestive heart failure, stroke, transient ischemic attack, and peripheral vascular disease) were adjudicated by an independent clinical endpoint committee. Hospitalizations due to adverse events that were not efficacy endpoints were reported by investigators on a dedicated case report form. In addition, hospitalizations for efficacy endpoints not confirmed by adjudication were classified as adverse events.
Total hospitalizations were analyzed with a competing risks marginal model for total events. The likelihood of no days lost to hospitalization and death, and the rate of days lost among those who were hospitalized or died during the study were analyzed with a zero-inflated Poisson regression model.
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Key results |
Over the median follow-up of 5.0 years there were 6,919 total hospitalizations, 3000 (43.4%) due to efficacy endpoints, and 3919 (56.6%) due to adverse events.
Treatment with icosapent ethyl treatment led to 313 fewer hospitalizations than placebo, driven entirely by efficacy endpoints (334 fewer hospitalizations than placebo). Over the total follow-up period, treatment with icosapent ethyl was associated with reduced risk of hospitalization(hazard ratio 0.91, 95% confidence interval [CI] 0.84 – 0.98, p=0.017) (Table 1). Compared with placebo, patients allocated to treatment with icosapent ethyl were more likely to survive until the end of the study without hospitalization (odds ratio 1.12, 95% CI 1.02 – 1.22, p=0.016). Among those who were hospitalized or died, patients in the icosapent ethyl group had significantly fewer days lost than those on placebo (relative risk 0.93, 95% CI 0.93 – 0.94, p<0.001) (Table 1).
Table 1. Days lost due to hospitalization or death
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Author conclusions |
Icosapent ethyl was associated with fewer total hospitalizations and fewer days lost due to hospitalization and death, providing additional insights on the effects of icosapent ethyl on patient-centred measures of total disease burden. |
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Comment
REDUCE-IT conclusively demonstrated the clinical benefit associated with treatment with icosapent ethyl in high cardiovascular risk patients on statin therapy with elevated triglycerides, reducing the risk of both first and total cardiovascular events relative to placebo (1,2). This latest analysis from REDUCE-IT shows that these clinical benefits translate to reduction in total disease burden, specifically with fewer hospitalizations and days lost due to hospitalization or death. Treatment with icosapent ethyl increased the likelihood that patients survived to the end of the study without hospitalization. Furthermore, for those patients who were subsequently hospitalized or died, there was reduction in the rate of days lost to either event during the study.
These findings have important implications given the substantial economic burden associated with management of cardiovascular disease. For example, in the European Union, this cost has been estimated at over EUR 282 billion (3). As advances in prevention, diagnosis, and treatment have extended survival, the number of people living with cardiovascular disease has increased. Consequently, the primary cost driver is no longer the treatment of acute, life‑threatening episodes, but the ongoing management of chronic disease. Indeed, in 2023, cardiovascular disease was the leading cause of hospitalizations across the majority of EU Member States, responsible for 9.2 million hospital admissions (4), representing the highest direct cost to total disease burden. Prolonged hospital stays also confer a large societal burden due to high direct medical costs associated with treatment and care, as well as high indirect costs due to lost productivity and caregiver burden.
Despite the caveats associated with post hoc analyses, these findings have important implications, extending evidence for the beneficial effects associated with icosapent ethyl treatment. With nearly 100 hospitalizations per 100 patients in the placebo group over the 5-year follow-up period of REDUCE-IT, reduction in this rate with icosapent ethyl implies favourable impact on the total disease burden in these high-risk patients with elevated triglycerides.
References
- Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22.
- Bhatt DL, Steg PG, Miller M, et al. Effects of icosapent ethyl on total ischemic events: from REDUCE-IT. J Am Coll Cardiol 2019;73:2791-802.
- Luengo-Fernandez R, Walli-Attaei M, Gray A,et al. Economic burden of cardiovascular diseases in the European Union: a population-based cost study. Eur Heart J 2023; 44; 4752-67.
- Eurostat (2023), Hospital discharges and length of stay statistics, https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Hospital_discharges_and_length_of_stay_statistics.
Key words: REDUCE-IT; icosapent ethyl, hospitalizations, total disease ab
