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

ABSTRACT

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.

KEYWORDS:

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

Declaration of interest

KV has received honoraria from Amarin Pharma Inc., Amgen, AstraZeneca, Aventyn, Baylor Research Institute, Boehringer Ingelheim, Legacy Heart, Novartis, Novo Nordisk, and ZS, and has received salary from Abrazo and the Scottsdale Cardiovascular Center.

HMS has received research grants from Akebia, Bayer, BioPorto, and La Jolla Pharmaceutical; serves on the speakers bureau for Astute Medical; has received honoraria from the Cardiorenal Society; has ownership interest in Amgen, Gilead, Merck, and Pfizer; is a consultant to and member of the advisory board of La Jolla Pharmaceutical; and has received product royalties/licensing fees from UptoDate.

CMB has received research/grant support from Abbott Diagnostics, Amarin Pharma Inc., Amgen, Esperion, Ionis, Novartis, Pfizer, Regeneron, Roche Diagnostic, Sanofi-Synthelabo, NIH, ADA, and AHA (all paid to institution, not individual), and is a consultant for Abbott Diagnostics, Amarin Pharma Inc., Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Esperion, Ionis, Matinas Biopharma, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostics, and Sanofi-Synthelabo.

Neither HEB nor his affiliated research center & weight management center own pharmaceutical stocks or patents. In the past 12 months, HEB’s research site has received research grants from Amarin Pharma Inc., Amgen, Alere, Allergan, AstraZeneca, Boehringer Ingelheim, Bristol Meyers Squibb, Catabasis, Dr. Reddy, Eisai, Elcelyx, Eli Lilly, Esperion, Ferrer/Chiltern, Gemphire, Gilead, GSK, Home Access, iSpecimen, Ionis, Janssen, Johnson and Johnson, Merck, Nektar, Nichi-Iko, Novartis, NovoNordisk, Omthera, Pfizer, Regeneron, Sanofi, Selecta, Takeda, and TIMI. In the past 12 months, HEB has served as a consultant/advisor for Alnylam, Akcea, Amgen, AstraZeneca, Eisai, Eli Lilly, Esperion, Ionis, Janssen, Johnson & Johnson, Kowa, Merck, Novartis, Prosciento, Regeneron, and Sanofi. In the past 12 months, HEB has served as a speaker for Amarin Pharma Inc., Amgen, Eisai, Kowa, Orexigen, Regeneron, and Sanofi.

SP, RTD Jr, RAJ, and CG are employees and stock shareholders in Amarin Corporation, the parent company of Amarin Pharma Inc.

Medical writing and editorial assistance was provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by Amarin Pharma Inc., Bedminster, NJ.

PGM peer reviewers on this manuscript have no disclosures of interest to report.

Additional information

Funding

This manuscript was funded by Amarin Pharma Inc.