Amarin Corp Plc (AMRN)

[lettruthringout]

HIGHER DHA LEVELS LOWER PROTECTIVE IMPACT OF EPA


Background:

Omega 3 polyunsaturated fatty acids (OM3-PUFA) are frequently used for cardiovascular prevention. While high dose eicosapentaenoic acid (EPA) reduces major adverse cardiovascular events (MACE)(JELIS, REDUCE-IT), combined EPA/docosahexaenoic acid (DHA) does not (STRENGTH, OMEMI). To clarify this, we compared the effects of EPA only, DHA only, and adjusted for one another on 10-y MACE.

Methods:

We used rapid throughput liquid chromatography-mass spectrometry to quantify plasma levels of EPA and DHA in 987 consenting patients (pts) undergoing angiography. 10-y MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization) was analyzed using Cox proportional hazard regression in 4 models: EPA only; DHA only; adjusted for one another, unadjusted/adjusted for severe CAD, COPD, and heart failure.

Results:

Age averaged 61.5 ± 12.15 y, 57% were male, 41% were obese, 42% had severe CAD, and 311 (31.5%) had a MACE. In the EPA only model, pts with the highest levels (Q4) were less likely to have a MACE (HR= 0.48 for Q4 vs Q1; 0.71 for Q2/Q3 vs Q1)(Figure). DHA alone was not associated with MACE. In both models EPA and DHA, EPA HRs decreased for high EPA, and pts with the lowest DHA levels were less likely to have a MACE.

Conclusion:

Higher levels of EPA but not DHA are associated with reductions in MACE. When combined with EPA, higher DHA blunts the benefit of EPA and increases MACE in the presence of low EPA, a novel finding. These findings may explain the discrepancy in clinical trial results.

https://www.abstractsonline.com/pp8/#!/9228/presentation/12635