Advertisement

Efficacy and Safety of Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Statin-Treated Patients With Persistent High Triglycerides (from the ANCHOR Study)

      AMR101 is an ω-3 fatty acid agent containing ≥96% pure icosapent-ethyl, the ethyl ester of eicosapentaenoic acid. The efficacy and safety of AMR101 were evaluated in this phase 3, multicenter, placebo-controlled, randomized, double-blinded, 12-week clinical trial (ANCHOR) in high-risk statin-treated patients with residually high triglyceride (TG) levels (≥200 and <500 mg/dl) despite low-density lipoprotein (LDL) cholesterol control (≥40 and <100 mg/dl). Patients (n = 702) on a stable diet were randomized to AMR101 4 or 2 g/day or placebo. The primary end point was median percent change in TG levels from baseline versus placebo at 12 weeks. AMR101 4 and 2 g/day significantly decreased TG levels by 21.5% (p <0.0001) and 10.1% (p = 0.0005), respectively, and non-high-density lipoprotein (non-HDL) cholesterol by 13.6% (p <0.0001) and 5.5% (p = 0.0054), respectively. AMR101 4 g/day produced greater TG and non-HDL cholesterol decreases in patients with higher-efficacy statin regimens and greater TG decreases in patients with higher baseline TG levels. AMR101 4 g/day decreased LDL cholesterol by 6.2% (p = 0.0067) and decreased apolipoprotein B (9.3%), total cholesterol (12.0%), very-low-density lipoprotein cholesterol (24.4%), lipoprotein-associated phospholipase A2 (19.0%), and high-sensitivity C-reactive protein (22.0%) versus placebo (p <0.001 for all comparisons). AMR101 was generally well tolerated, with safety profiles similar to placebo. In conclusion, AMR101 4 g/day significantly decreased median placebo-adjusted TG, non-HDL cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, lipoprotein-associated phospholipase A2, and high-sensitivity C-reactive protein in statin-treated patients with residual TG elevations.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ford E.S.
        • Li C.
        • Zhao G.
        • Pearson W.S.
        • Mokdad A.H.
        Hypertriglyceridemia and its pharmacologic treatment among US adults.
        Arch Intern Med. 2009; 169: 572-578
        • National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
        Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • Miller M.
        • Stone N.J.
        • Ballantyne C.
        • Bittner V.
        • Criqui M.H.
        • Ginsberg H.N.
        • Goldberg A.C.
        • Howard W.J.
        • Jacobson M.S.
        • Kris-Etherton P.M.
        • Lennie T.A.
        • Levi M.
        • Mazzone T.
        • Pennathur S.
        • American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and Metabolism, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Cardiovascular Nursing, Council on the Kidney in Cardiovascular Disease
        Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association.
        Circulation. 2011; 123: 2292-2333
        • Bays H.E.
        • Ballantyne C.M.
        • Kastelein J.J.
        • Isaacsohn J.L.
        • Braeckman R.A.
        • Soni P.N.
        Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial).
        Am J Cardiol. 2011; 108: 682-690
        • Davidson M.H.
        • Stein E.A.
        • Bays H.E.
        • Maki K.C.
        • Doyle R.T.
        • Shalwitz R.A.
        • Ballantyne C.M.
        • Ginsberg H.N.
        • COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators
        Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study.
        Clin Ther. 2007; 29: 1354-1367
        • Bays H.E.
        • McKenney J.
        • Maki K.C.
        • Doyle R.T.
        • Carter R.N.
        • Stein E.
        Effects of prescription omega-3-acid ethyl esters on non–high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin.
        Mayo Clin Proc. 2010; 85: 122-128
        • Davidson M.H.
        • Maki K.C.
        • Bays H.
        • Carter R.
        • Ballantyne C.M.
        Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A(2) mass in statin-treated subjects with hypertriglyceridemia.
        J Clin Lipidol. 2009; 3: 332-340
      1. Lovaza (package insert).
        GlaxoSmithKline, Research Triangle Park, NC2010
        • Schaefer E.J.
        • Asztalos I.B.
        • Gleason J.A.
        • Asztalos B.F.
        • Horvath K.
        • Dansinger M.L.
        • Gillies P.J.
        Effects of eicosapentaenoic acid, docosahexaenoic acid, and olive oil on cardiovascular disease risk factors (abstract 20007).
        Circulation. 2010; 122: a20007
        • Keech A.
        • Simes R.J.
        • Barter P.
        • Best J.
        • Scott R.
        • Taskinen M.R.
        • Forder P.
        • Pillai A.
        • Davis T.
        • Glasziou P.
        • Drury P.
        • Kesäniemi Y.A.
        • Sullivan D.
        • Hunt D.
        • Colman P.
        • d'Emden M.
        • Whiting M.
        • Ehnholm C.
        • Laakso M.
        • FIELD study investigators
        Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.
        Lancet. 2005; 366: 1849-1861
        • Ginsberg H.N.
        • Elam M.B.
        • Lovato L.C.
        • Crouse III, J.R.
        • Leiter L.A.
        • Linz P.
        • Friedewald W.T.
        • Buse J.B.
        • Gerstein H.C.
        • Probstfield J.
        • Grimm R.H.
        • Ismail-Beigi F.
        • Bigger J.T.
        • Goff Jr, D.C.
        • Cushman W.C.
        • Simons-Morton D.G.
        • Byington R.P.
        • ACCORD Study Grouop
        Effects of combination lipid therapy in type 2 diabetes mellitus.
        N Engl J Med. 2010; 362: 1563-1574
        • Boden W.E.
        • Probstfield J.L.
        • Anderson T.
        • Chaitman B.R.
        • Desvignes-Nickens P.
        • Koprowicz K.
        • McBride R.
        • Teo K.
        • Weintraub W.
        • AIM-HIGH Investigators
        Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy.
        N Engl J Med. 2011; 365: 2255-2267
        • Bays H.
        Fish oils in the treatment of dyslipidemia and cardiovascular disease.
        in: Kwiterovich P.O. The Johns Hopkins Textbook of Dyslipidemia. Lippincott Williams & Wolters Kluwer, Philadelphia, PA2010: 245-257
        • Kris-Etherton P.M.
        • Harris W.S.
        • Appel L.J.
        • AHA Nutrition Committee, American Heart Association
        Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association.
        Arterioscler Thromb Vasc Biol. 2003; 23: 151-152
        • Yokoyama M.
        • Origasa H.
        • Matsuzaki M.
        • Matsuzawa Y.
        • Saito Y.
        • Ishikawa Y.
        • Oikawa S.
        • Sasaki J.
        • Hishida H.
        • Itakura H.
        • Kita T.
        • Kitabatake A.
        • Nakaya N.
        • Sakata T.
        • Shimada K.
        • Shirato K.
        • Japan EPA lipid intervention study (JELIS) Investigators
        Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.
        Lancet. 2007; 369: 1090-1098

      Linked Article

      • ANCHOR Trial Conclusions Regarding the Effects of Pure Eicosapentaenoic Acid on Low-Density Lipoprotein Cholesterol
        American Journal of CardiologyVol. 111Issue 3
        • Preview
          In the ANCHOR trial publication, Ballantyne et al,1 evaluating AMR101 (icosapent ethyl) for the treatment of mixed dyslipidemia, concluded that omega-3 fatty acids containing only eicosapentaenoic acid (EPA) lower low-density lipoprotein (LDL) cholesterol. The investigators' interpretation of the data regarding the effects of pure EPA on LDL cholesterol is misleading for 2 important reasons. First, the placebo used in the AMR101 trials was light liquid paraffin, more commonly known as mineral oil, a biologically active substance.
        • Full-Text
        • PDF