Effects of icosapent ethyl on risk and duration of hospitalizations and death in REDUCE-IT

Abstract Background Among participants with elevated triglycerides and known cardiovascular disease or with diabetes and other risk factors in the REDUCE-IT trial, icosapent ethyl (IPE) significantly reduced the risk of first and total cardiovascular events relative to placebo. Purpose The aim of this post hoc analysis of the trial was to estimate the effects of IPE on total hospitalizations and days lost to hospitalization and death. Methods Randomization to treatment with 2 g twice daily of IPE or matching placebo was performed among 8179 participants receiving statin therapy with established cardiovascular disease or age ≥50 years with diabetes and ≥1 additional risk factor, fasting triglyceride 1.69 – 5.63 mmol/L, and low-density lipoprotein cholesterol 1.06 – 2.59 mmol/L. Total hospitalizations were analyzed with a competing risks marginal proportional hazards 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. Results During a median 5.0 years of follow-up, 6919 total hospitalizations were observed, with median (Q1, Q3) duration of 4 (2, 10) days. IPE reduced total hospitalizations (HR (95% CI) = 0.91 (0.84, 0.98), P=0.017; Figure). Participants randomized to IPE were also more likely to survive until the end of the study without hospitalization (OR (95% CI) = 1.12 (1.02, 1.22), P=0.016) and had a lower rate of days lost among those who were hospitalized or died during follow-up (RR (95% CI) = 0.93 (0.93, 0.94), P0.001). Normalizing for duration of follow-up, 19.2 total hospitalizations and 21.4 total hospitalizations or deaths were avoided with IPE per 1000 participant-years of assigned treatment. Conclusion Among participants in REDUCE-IT, IPE reduced total hospitalizations and had favorable impacts on measures of days lost due to hospitalization and death. These findings provide additional insights on the effects of IPE on patient-centered measures of total disease burden.