Effect of icosapent ethyl on stroke risk: Different strokes for different folks?

  • Meng Lee
    Correspondence
    Corresponding author at: Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi branch, 6 West Section, Chiapu Road, Puzi 613, Taiwan.
    Affiliations
    Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
    Search for articles by this author
  • Bruce Ovbiagele
    Affiliations
    Department of Neurology, University of California, San Francisco, CA, USA
    Search for articles by this author
Published:April 19, 2019DOI:https://doi.org/10.1016/j.jns.2019.04.027
      In the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) [
      • Bhatt D.L.
      • Steg P.G.
      • Miller M.
      • Brinton E.A.
      • Jacobson T.A.
      • Ketchum S.B.
      • et al.
      Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.
      ], among patients with elevated triglycerides on statins, ischemic event risk was lower among those who received icosapent ethyl vs. placebo. However, while coronary events were reduced in both REDUCE-IT and another pure EPA trial, Japan EPA lipid intervention study (JELIS) [
      • Yokoyama M.
      • Origasa H.
      • Matsuzaki M.
      • Matsuzawa Y.
      • Saito Y.
      • Ishikawa Y.
      • et al.
      Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.
      ], ischemic stroke risk was lowered in REDUCE-IT (HR 0.64, 0.49-0.85), but not decreased in JELIS (HR 0.97, 0.85-1.10). The discrepancy between these two pure EPA trials might be due to the varied race-ethnicity composition of participants, since participants in REDUCE-IT were mostly from the USA and Europe, while those in JELIS were all from Japan. Although most ischemic strokes are caused by underlying atherosclerosis, non-atherosclerotic intracranial diseases (e.g. moyamoya, dissection) are more common among Asians [
      • Kim J.S.
      • Kim Y.J.
      • Ahn S.H.
      • Kim B.J.
      Location of cerebral atherosclerosis: why is there a difference between east and west?.
      ]. Moreover, extracranial atherosclerosis, which is more common in Caucasians is more aligned in pathogenesis to coronary atherosclerosis than intracranial atherosclerosis, the latter of which is more prevalent in East Asians [
      • Kim J.S.
      • Kim Y.J.
      • Ahn S.H.
      • Kim B.J.
      Location of cerebral atherosclerosis: why is there a difference between east and west?.
      ]. It is worthwhile to mention that different daily doses of EPA (4 g in REDUCE-IT vs 1.8 g in JELIS, respectively) were used and could be a possible explanation for why there was a significant reduction in stroke in REDUCE-IT but not in JELIS since a recent cohort study suggested that adipose tissue content of EPA was inversely associated with total ischemic stroke [
      • Venø S.K.
      • Bork C.S.
      • Jakobsen M.U.
      • Lundbye-Christensen S.
      • McLennan P.L.
      • Bach F.W.
      • et al.
      Marine n-3 polyunsaturated fatty acids and the risk of ischemic stroke.
      ]. Additional investigation into the stroke protective benefits of icosapent ethyl among East Asians is warranted.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bhatt D.L.
        • Steg P.G.
        • Miller M.
        • Brinton E.A.
        • Jacobson T.A.
        • Ketchum S.B.
        • et al.
        Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.
        N. Engl. J. Med. 2019; 380: 11-22
        • Yokoyama M.
        • Origasa H.
        • Matsuzaki M.
        • Matsuzawa Y.
        • Saito Y.
        • Ishikawa Y.
        • et al.
        Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.
        Lancet. 2007; 369: 1090-1098
        • Kim J.S.
        • Kim Y.J.
        • Ahn S.H.
        • Kim B.J.
        Location of cerebral atherosclerosis: why is there a difference between east and west?.
        Int. J. Stroke. 2018; 13: 35-46
        • Venø S.K.
        • Bork C.S.
        • Jakobsen M.U.
        • Lundbye-Christensen S.
        • McLennan P.L.
        • Bach F.W.
        • et al.
        Marine n-3 polyunsaturated fatty acids and the risk of ischemic stroke.
        Stroke. 2019; 50: 274-282