Icosapent ethyl modulates circulating vascular regenerative cell content: The IPE-PREVENTION CardioLink-14 trial

Area of Science:

• Cardiovascular Medicine
• Translational Science
• Regenerative Medicine

Background:

• The REDUCE-IT trial demonstrated icosapent ethyl (IPE) reduced cardiovascular events by 25%.
• Mechanisms underlying IPE's cardioprotective effects remain incompletely understood.
• The IPE-PREVENTION CardioLink-14 trial investigated IPE's impact on vascular regenerative cells.

Purpose of the Study:

• To determine if IPE regulates vascular regenerative (VR) cell content in patients with mild to moderate hypertriglyceridemia.
• To explore potential novel mechanisms for IPE's cardioprotective action.

Main Methods:

• Seventy statin-treated patients with hypertriglyceridemia were randomized to IPE or usual care.
• Vascular regenerative cells with high aldehyde dehydrogenase activity (ALDH^hi) were isolated and characterized.
• Primary endpoint: change in frequency of pro-vascular ALDH^hiCD133⁺ progenitor cells.

Main Results:

• IPE significantly increased the frequency of ALDH^hiCD133⁺ progenitor cells compared to usual care.
• IPE reduced oxidative stress in ALDH^hiSSC^low progenitors.
• IPE also increased ALDH^hiSSC^hi granulocyte precursor cell content.

Conclusions:

• IPE-PREVENTION CardioLink-14 provides the first translational evidence of IPE modulating VR cell content.
• This modulation of VR cells suggests a novel mechanism for IPE's cardioprotective effects.
• Findings support further investigation into IPE's role in vascular regeneration and cardiovascular event reduction.