QUEBEC CITY — Treating patients with established cardiovascular disease (CVD) or other high-risk factors for CV events with icosapent ethyl (IPE) may help reduce the risk for days lost to hospitalization or death, according to a post hoc analysis of the REDUCE-IT study. The findings, which were largely driven by a reduction in risk for death, were presented at the Canadian Cardiovascular Congress (CCC) 2025. 

“Hospitalizations are an important component of total disease burden for individuals who are at higher risk for cardiovascular events,” said lead author Michael Szarek, PhD, research professor of cardiology at the University of Colorado School of Medicine in Aurora, Colorado, during his presentation.

The multicenter REDUCE-IT trial examined 8179 patients with established CVD or diabetes and other CV risk factors who had been receiving statin therapy and who had a fasting triglyceride level of 135-499 mg/dL (1.52-5.63 mmol/L) and a low-density lipoprotein level of 41-100 mg/dL (1.06-2.59 mmol/L). Participants were randomly assigned to receive placebo or 2 g IPE twice daily.

Among patients who received active therapy, the rate of the composite endpoint of CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina was 17.2% after a median of 4.9 years compared with 22.0% in the placebo group (hazard ratio [HR], 0.75; P < .001).

Post Hoc Analysis

Overall, 4764 patients in the trial remained alive and had no hospitalizations, whereas 3415 died or were hospitalized at least once. As expected, those in the latter group were older, had higher BMI, and were more likely to have CV risk factors.

Among patients who received IPE, 3303 were hospitalised for any reason compared with 3616 in the placebo group. Approximately 43% of hospitalizations were associated with efficacy outcomes in the REDUCE-IT trial, and the remainder were attributed to adverse events.

After the data were normalized for duration of follow-up, they showed that 19.2 total hospitalizations and 21.5 total hospitalizations or deaths per 1000 patient-years had been avoided with IPE treatment. Mean cumulative functions for total hospitalizations over 5 years indicated a rate of 89.1 hospitalizations per 100 patients in the IPE group compared with 98.9 per 100 patients in the placebo group (HR, 0.91; P = .017).

Toward Greater Prevention

The mean number of days lost to hospitalization or death was 75 in the IPE group, compared with 86 in the placebo group. The mean days lost to hospitalization was 14 in both groups, “so that difference overall in days lost to hospitalization or death was really due to a difference in days dead, with a mean of 61 days for IPE vs 72 for placebo,” said Szarek.

The proportion of patients with no days lost to hospitalization or death was 59.5% in the IPE group and 57.0% in the placebo group (P = .016). Similarly, the mean number of patients with at least 1 day lost was 187 with IPE and 201 without (P < .001).

Though study participants were well-treated for their condition, the rate of hospitalization was high, said Szarek, “Reduction in all-cause hospitalization by IPE was entirely due to reduction in the efficacy endpoint hospitalizations. In contrast, all-cause adverse event hospitalizations were nominally more frequent in both treatment groups, and their incidence was not impacted by IPE treatment.”

Szarek acknowledged that the limitations of the analysis include its post hoc nature and the researchers’ inability to identify hospitalizations that were not due to trial efficacy endpoints or adverse events.

“These findings find provide additional evidence of the beneficial effects of IPE on patient-centered measures of total disease burden,” he concluded.

The findings are important because “we want to do more prevention with our patients,” Léa Berbach, PhD, of the Centre Hospitalier de L’Université de Montréal, told Medscape Medical News. “Preventing people from [dying or going] to the hospital is our main goal.” Berbach chaired the session but was not involved in the REDUCE-IT study.

She noted that the trial focused on a specific patient population, so it is impossible to know whether IPE treatment would have a similar effect on a wider array of cardiac patients. Another limitation is that more information on the underlying causes of death and hospitalization is needed, she said. This endpoint should be investigated in a larger and varied group of patients, with consideration given to potential sex differences in the outcomes, Berbach concluded.

REDUCE-IT was funded by Amarin Pharma. Szarek reported receiving support from Lexicon, Amarin, New Amsterdam Pharma, Novartis, Silence, Sanofi, Regeneron, Tourmaline, and CPC (a nonprofit academic research organisation affiliated with the University of Colorado that has received funding from multiple commercial and noncommercial sources). Berbach reported having no relevant financial relationships.