REDUCE-IT — Icosapent Ethyl in High-Triglyceride ASCVD Patients

Design

REDUCE-IT randomised 8,179 patients with established ASCVD or diabetes plus other risk factors, on statin therapy, with triglycerides 135–499 mg/dL, to icosapent ethyl (pure EPA, 2 g twice daily) or placebo (mineral oil), median follow-up 4.9 years.

Findings

• Primary composite (CV death, non-fatal MI, non-fatal stroke, coronary revascularisation, unstable angina): 25% relative reduction (HR 0.75).
• Key secondary (CV death, MI, stroke): 26% reduction.
• Triglyceride reduction: ~18%.
• Atrial fibrillation: modest increase, statistically significant.
• Major bleeding: modest increase.

The mineral-oil controversy

The placebo arm received mineral oil. Subsequent analysis suggested mineral oil may have small adverse effects on LDL and hsCRP, raising questions about how much of the effect was “true” benefit of icosapent ethyl versus relative harm of the placebo. The STRENGTH trial of a similar EPA+DHA preparation against a corn-oil placebo was negative, adding to the uncertainty.

What people draw from it

• High-dose pure EPA is now an option in eligible patients on statin therapy with persistent hypertriglyceridaemia.
• Generic omega-3 supplements at lower doses do not provide the same benefit.
• The AF and bleeding signals deserve consideration.

Related entries

Omega-3, Atrial fibrillation, Cardiovascular disease.