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Postgrad Med. 2019 Jul 25:1-7. doi: 10.1080/00325481.2019.1643633. [Epub ahead of print]

Icosapent ethyl reduces atherogenic markers in high-risk statin-treated patients with stage 3 chronic kidney disease and high triglycerides.

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a Institute of Congestive Heart Failure, Abrazo Arizona Heart Hospital , Phoenix , AZ , USA.
b Nephrology Division and Nephrology Fellowship Program, Baylor University Medical Center , Dallas , TX , USA.
c Department of Medicine, Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center , Houston , TX , USA.
d Louisville Metabolic and Atherosclerosis Research Center , Louisville , KY , USA.
e Medical Affairs, Amarin Pharma Inc ., Bedminster , NJ , USA.
f Clinical Development, Amarin Pharma Inc ., Bedminster , NJ , USA.


Objective: Patients with chronic kidney disease (CKD) have increased cardiovascular disease (CVD) risk, likely driven by atherogenic and inflammatory markers beyond low-density lipoprotein cholesterol (LDL-C). The objective of this hypothesis-generating post hoc subgroup analysis was to explore the effects of icosapent ethyl at 2 or 4 g/day (prescription pure ethyl ester of the omega-3 fatty acid eicosapentaenoic acid [EPA]) on atherogenic lipid, apolipoprotein, inflammatory parameters (high-sensitivity C-reactive protein [hsCRP], lipoprotein-associated phospholipase A2 [Lp-PLA2]), and oxidative parameters (oxidized-LDL [ox-LDL]) in statin-treated patients from ANCHOR with stage 3 CKD. Methods: The 12-week ANCHOR study evaluated icosapent ethyl in 702 statin-treated patients at increased CVD risk with triglycerides (TG) 200-499 mg/dL despite controlled LDL-C (40-99 mg/dL). This post-hoc analysis included patients from ANCHOR with stage 3 CKD (estimated glomerular filtration rate [eGFR] ≤60 mL/min/1.73 m2 for ≥3 months) randomized to icosapent ethyl 4 g/day (n = 19), 2 g/day (n = 30), or placebo (n = 36). Results: At the prescription dose of 4 g/day, icosapent ethyl significantly reduced TG (-16.9%; P = 0.0074) and other potentially atherogenic lipids/lipoproteins, ox-LDL, hsCRP, and Lp-PLA2, and increased plasma and red blood cell EPA levels (+879% and +579%, respectively; both P < 0.0001) versus placebo. Icosapent ethyl did not significantly alter eGFR or serum creatinine. Safety and tolerability were similar to placebo. Conclusions: In patients with stage 3 CKD at high CVD risk with persistent high TG despite statins, icosapent ethyl 4 g/day reduced potentially atherogenic and other cardiovascular risk factors without raising LDL-C, with safety similar to placebo. These findings suggest prospective investigation may be warranted.


Cardiovascular disease; chronic kidney disease; chronic renal insufficiency; eicosapentaenoic acid; hypertriglyceridemia; icosapent ethyl

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