Abstract 15097: Icosapent Ethyl Reduces Potentially Atherogenic Lipid and Inflammatory Markers in High-Risk Statin-Treated Patients With Stage 3 Chronic Kidney Disease and Persistent High Triglycerides
Introduction: Patients with chronic kidney disease (CKD) have increased cardiovascular disease (CVD) risk. Atherogenic and inflammatory markers beyond LDL-C likely drive this risk, but data are lacking in this population. Icosapent ethyl (IPE) is a prescription high-purity ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA) approved at 4 g/day as an adjunct to diet to reduce triglycerides (TG) in adults with TG ≥500 mg/dL.
Methods: The 12-week ANCHOR study randomized 702 statin-treated patients at increased CVD risk with TG 200-499 mg/dL despite LDL-C control (40-99 mg/dL). Stage 3 CKD (estimated glomerular filtration rate [eGFR] ≤60 mL/min/1.73 m2 for ≥3 months) was present in 83 patients (96% white; mean age, 68 y) at baseline. This post hoc analysis assessed ANCHOR patients with stage 3 CKD at baseline randomized to IPE 4 g/d (n=18; eGFR min, max: 24.7, 59.7 mL/min/1.73 m2) or placebo (n=35; eGFR min, max: 32.7, 59.6 mL/min/1.73 m2). Endpoints included nonparametric analyses of median percent change from baseline to week 12 in fasting lipids, lipoproteins, inflammatory markers, and EPA concentrations vs placebo.
Results: IPE 4 g/day reduced TG (-17%; P=0.007) and other potentially atherogenic parameters vs placebo without raising LDL-C (Figure). There were no significant changes in eGFR or serum creatinine. EPA levels increased 879% in plasma and 579% in RBCs vs placebo (both P<0.0001).
Conclusions: In patients with stage 3 CKD at high CVD risk with persistent high TG despite statins, IPE 4 g/day reduced potentially atherogenic and other CV risk factors without raising LDL-C with safety generally similar to placebo. It is unclear if therapies beyond statins that lower CV risk factors improve outcomes in CKD patients; these hypothesis-generating findings suggest prospective investigation may be warranted. The ongoing CV outcomes trial with prescription high-dose pure EPA as a statin adjunct (REDUCE-IT) will also include some patients with CKD.
Author Disclosures: K. Vijayaraghavan: Employment; Modest; Arizona Heart Hospital. Speakers Bureau; Modest; Boehringer Ingelheim, Novartis, Amgen, AstraZeneca, Sanofi, Amarin Pharma. Honoraria; Modest; Relypsa, Lilly. Consultant/Advisory Board; Modest; Kowa, ZS Pharma, Aventyn. H.M. Szerlip: Research Grant; Modest; La Jolla Pharmaceutical, Bayer, Akebia, BioPorto. Speakers Bureau; Modest; Astute Medical. Honoraria; Modest; Cardiorenal Society. Ownership Interest; Modest; Pfizer, Merck, Amgen, Gilead. Consultant/Advisory Board; Modest; La Jolla Pharmaceutical. Other; Modest; UptoDate. C.M. Ballantyne: Other Research Support; Modest; NIH, ADA, AHA, Ionis, Amarin Pharma Inc., Amgen, Eli Lilly, Esperion, Novartis, Pfizer, Regneron, Sanofi-Synthelabo. Consultant/Advisory Board; Modest; Amarin Pharma Inc., Amgen, Astra Zeneca, Boehringer Ingelheim, Esperion, Eli Lilly, Ionis, Matinas BioPharma Inc., Merck, Novartis, Pfizer, Regeneron, Sanofi-Synthelabo. H.E. Bays: Research Grant; Significant; Amarin Pharma Inc., Amgen, Alere, Allergan, Arisaph, AstraZeneca, Bristol Myers Squibb, Catabasis, Cymabay, Dr. Reddy, Eisai, Elcelyx, Eli Lilly, Esperion, Ferrer/Chiltern, Gemphire, Gilead, GSK, Janssen, Johnson & Johnson, Kowa, Merck, Nektar, Nichi-Iko, Novartis, NovoNordisk, Orexigen, Pfizer, Pronova, Regeneron, Sanofi, Takeda, TIMI. Speakers Bureau; Modest; AstraZeneca, Eisai, Regeneron, Sanofi, Takeda. Speakers Bureau; Significant; Amarin Pharma Inc., Amgen, Orexigen. Consultant/Advisory Board; Modest; Alnylam, Akcea, Amgen, AstraZeneca, Eli Lilly, Esperion, Ionis (ISIS), Janssen, Johnson & Johnson, Kowa, Merck, Novartis, Procter & Gamble, Teva, Takeda. Consultant/Advisory Board; Significant; Regeneron, Sanofi. Other; Modest; Moderna. S. Philip: Employment; Significant; Amarin Pharma Inc.. Ownership Interest; Significant; Amarin Pharma Inc. R.T. Doyle: Employment; Significant; Amarin Pharma Inc.. Ownership Interest; Modest; Amarin Pharma Inc. R.A. Juliano: Employment; Significant; Amarin Pharma Inc.. Ownership Interest; Modest; Amarin Pharma Inc. C. Granowitz: Employment; Significant; Amarin Pharma Inc.. Ownership Interest; Significant; Amarin Pharma Inc..
- © 2017 by American Heart Association, Inc.