Consistent benefit of icosapent ethyl across background statin agent and category

Consistency of Benefit of Icosapent Ethyl by Background Statin Type in REDUCE-IT

Literature - Singh N, Bhatt DL, Miller M et al., - J Am Coll Cardiol. 2022 Jan 18;79(2):220-222. doi: 10.1016/j.jacc.2021.11.005.


Icosapent ethyl (IPE) 4 g daily reduced CV events in high-risk patients with elevated triglycerides despite LDL-c control with statins in the REDUCE-IT trial [1]. There were beneficial lipid effects, but these did not explain the total CV benefit. Anti-inflammatory, antithrombotic, membrane stabilization, plaque stabilization, cholesterol crystal decreases and pro-endothelial effects may play a role. Statins also have nonlipid effects on CV events that may be related to lipophilicity. It is unknown whether the beneficial effects of IPE are modified by statins.

In this study, the effect of the type of background statin treatment on CV benefits of IPE was examined.

Study design

This exploratory analysis of REDUCE-IT, outcomes were examined in a time-to-first-event analysis, with subgroups based on statin agent and lipophilic vs. lipophobic statin category. Included statins were atorvastatin, simvastatin, rosuvastatin, and pravastatin. Lipophilic statins were atorvastatin and simvastatin and lipophobic statins included rosuvastatin and pravastatin.

Primary outcome

The primary outcome was a composite of CV death, MI, stroke, coronary revascularization or unstable angina.

Main results

  • There was no difference of IPE efficacy among statin agents (Pinteraction=0.95).
  • The primary outcome occurred at a rate of 18.1% in the IPE group vs. 22.0% in the placebo group among patients on lipophilic statins (HR 0.78, 95%CI:0.69-0.93, P<0.0001) and in patients on lipophobic statins, this was 15.8% in the IPE group and 20.8% in the placebo group, respectively (HR 0.75, 95%CI:0.61-0.93, P=0.007). This resulted in no difference in IPE efficacy among statin categories (Pinteraction=0.67).
  • Similar results were seen for the key secondary endpoint; no difference of treatment effect among statin agents or categories.


There were consistent benefits of IPE for outcomes across background statin agent and category (lipophilic or lipophobic). These results suggest that mechanisms that are modified by statin intensity, type of agent or lipophilicity are not main drivers of the clinical efficacy of IPE.


1. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019, 380:11-22, DOI: 10.1056/NEJMoa1812792

Find this article online at J Am Coll Cardiol

Facebook Comments


We’re glad to see you’re enjoying PACE-CME…
but how about a more personalized experience?

Register for free