Combination Therapy with Statins and Omega-3 Fatty Acids

  • Vijay Nambi
    Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
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  • Christie M. Ballantyne
    Address for reprints: Christie M. Ballantyne, MD, Baylor College of Medicine, 6565 Fannin, MS A-601, Houston, Texas 77030.
    Section of Atherosclerosis and Lipid Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

    Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, Texas, USA.
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      Combined dyslipidemia is the concurrent presence of multiple abnormalities in various lipid subfractions, including elevated concentrations of low-density lipoprotein (LDL) cholesterol and triglycerides (TGs), as well as decreased concentrations of high-density lipoprotein (HDL) cholesterol. The Adult Treatment Panel III (ATP III) guidelines of the US National Cholesterol Education Program (NCEP) lowered the cut points for classification of TG levels, established non-HDL cholesterol levels as a secondary target of therapy in patients with TGs of ≥2.26 mmol/L (200 mg/dL), and defined the metabolic syndrome as a secondary target of therapy. Although 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are first-line therapy for most patients with elevated LDL cholesterol, statin monotherapy may not be sufficient to achieve recommended non-HDL cholesterol goals, and statins have only modest effects on reducing TG levels. Similarly, patients whose TG levels remain elevated despite treatment with a TG-lowering agent may require the addition of a statin to provide further TG reduction. In addition, statin therapy may be needed to offset the secondary increase in levels of LDL cholesterol that frequently results from treatment with a TG-lowering agent in patients with marked hypertriglyceridemia. In a number of small studies, the combination of statins and omega-3 fatty acids has been consistently shown to be an effective, safe, and well-tolerated treatment for combined dyslipidemia. Patients with recent myocardial infarction may also benefit from this combination. When considering risks and benefits of adding a second agent to statins for treatment of combined dyslipidemia, omega-3 fatty acids provide additional lipid improvements without requiring additional laboratory tests and do not increase risk for adverse muscle or liver effects.
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        • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
        Executive summary of the 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).
        JAMA. 2001; 285: 2486-2497
        • Assmann G.
        • Schulte H.
        Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience).
        Am J Cardiol. 1992; 70: 733-737
        • Stampfer M.J.
        • Krauss R.M.
        • Ma J.
        • Blanche P.J.
        • Holl L.G.
        • Sacks F.M.
        • Hennekens C.H.
        A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction.
        JAMA. 1996; 276: 882-888
        • Manninen V.
        • Tenkanen L.
        • Koskinen P.
        • Huttunen J.K.
        • Manttari M.
        • Heinonen O.P.
        • Frick M.H.
        Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study.
        Circulation. 1992; 85: 37-45
        • Lamarche B.
        • Moorjani S.
        • Lupien P.J.
        • Cantin B.
        • Bernard P.M.
        • Dagenais G.R.
        • Despres J.P.
        Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a five-year follow-up of men in the Quebec Cardiovascular Study.
        Circulation. 1996; 94: 273-278
        • Pownall H.J.
        • Brauchi D.
        • Kilinc C.
        • Osmundsen K.
        • Pao Q.
        • Payton-Ross C.
        • Gotto Jr, A.M.
        • Ballantyne C.M.
        Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins.
        Atherosclerosis. 1999; 143: 285-297
        • Weber P.
        • Raederstorff D.
        Triglyceride-lowering effect of omega-3 LC-polyunsaturated fatty acids—a review.
        Nutr Metab Cardiovasc Dis. 2000; 10: 28-37
        • Harris W.S.
        n-3 Fatty acids and serum lipoproteins.
        Am J Clin Nutr. 1997; 65: 1645S-1654S
        • Harris W.S.
        Fish oils and plasma lipid and lipoprotein metabolism in humans.
        J Lipid Res. 1989; 30: 785-807
        • Park Y.
        • Harris W.S.
        Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance.
        J Lipid Res. 2003; 44: 455-463
        • Contacos C.
        • Barter P.J.
        • Sullivan D.R.
        Effect of pravastatin and omega-3 fatty acids on plasma lipids and lipoproteins in patients with combined hyperlipidemia.
        Arterioscler Thromb. 1993; 13: 1755-1762
        • Nordøy A.
        • Bønaa K.H.
        • Nilsen H.
        • Berge R.K.
        • Hansen J.B.
        • Ingebretsen O.C.
        Effects of simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia.
        J Intern Med. 1998; 243: 163-170
        • Durrington P.N.
        • Bhatnagar D.
        • Mackness M.I.
        • Morgan J.
        • Julier K.
        • Khan M.A.
        • France M.
        An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia.
        Heart. 2001; 85: 544-548
        • Nordøy A.
        • Hansen J.B.
        • Brox J.
        • Svensson B.
        Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia.
        Nutr Metab Cardiovasc Dis. 2001; 11: 7-16
        • Chan D.C.
        • Watts G.F.
        • Mori T.A.
        • Barrett P.H.
        • Beilin L.J.
        • Redgrave T.G.
        Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity.
        Eur J Clin Invest. 2002; 32: 429-436
        • Yokoyama M.
        Effects of eicosapentaenoic acid (EPA) on major cardiovascular events in hypercholesterolemic patients. 2005 (Presented at the American Heart Association Scientific Sessions; November 14; Dallas, TX.)
        • Yokoyama M.
        • Origasa H.
        • JELIS Investigators
        Effects of eicosapentaenoic acid on cardiovascular events in Japanese patients with hypercholesterolemia.
        Am Heart J. 2003; 146: 613-620
        • GISSI-Prevenzione Investigators
        Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction.
        Lancet. 1999; 354: 447-455
        • Chin J.P.
        • Dart A.M.
        How do fish oils affect vascular function?.
        Clin Exp Pharmacol Physiol. 1995; 22: 71-81
        • McVeigh G.E.
        • Brennan G.M.
        • Cohn J.N.
        • Finkelstein S.M.
        • Hayes R.J.
        • Johnston G.D.
        Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus.
        Arterioscler Thromb. 1994; 14: 1425-1429
        • Calo L.
        • Bianconi L.
        • Colivicchi F.
        • Lamberti F.
        • Loricchio M.L.
        • de Ruvo E.
        • Meo A.
        • Pandozi C.
        • Staibano M.
        • Santini M.
        N-3 fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery.
        J Am Coll Cardiol. 2005; 45: 1723-1728
        • Leaf A.
        • Kang J.X.
        • Xiao Y.F.
        • Billman G.E.
        Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils.
        Circulation. 2003; 107: 2646-2652
        • Calder P.C.
        n-3 Fatty acids and cardiovascular disease.
        Clin Sci (Lond). 2004; 107: 1-11
        • Abe Y.
        • El-Masri B.
        • Kimball K.T.
        • Pownall H.
        • Reilly C.F.
        • Osmundsen K.
        • Smith C.W.
        • Ballantyne C.M.
        Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion.
        Arterioscler Thromb Vasc Biol. 1998; 18: 723-731
        • Lopez-Garcia E.
        • Schulze M.B.
        • Manson J.E.
        • Meigs J.B.
        • Albert C.M.
        • Rifai N.
        • Willett W.C.
        • Hu F.B.
        Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women.
        J Nutr. 2004; 134: 1806-1811
        • Zhao G.
        • Etherton T.D.
        • Martin K.R.
        • West S.G.
        • Gillies P.J.
        • Kris-Etherton P.M.
        Dietary α-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women.
        J Nutr. 2004; 134: 2991-2997
        • Krysiak R.
        • Okopien B.
        • Herman Z.
        Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes.
        Drugs. 2003; 63: 1821-1854
        • Schönbeck U.
        • Libby P.
        Inflammation, immunity, and HMG-CoA reductase inhibitors.
        Circulation. 2004; 109: II18-II26
        • Nordøy A.
        • Svensson B.
        • Hansen J.B.
        Atorvastatin and omega-3 fatty acids protect against activation of the coagulation system in patients with combined hyperlipemia.
        J Thromb Haemost. 2003; 1: 690-697
        • Chan D.C.
        • Watts G.F.
        • Barrett P.H.
        • Beilin L.J.
        • Mori T.A.
        Effect of atorvastatin and fish oil on plasma high-sensitivity C-reactive protein concentrations in individuals with visceral obesity.
        Clin Chem. 2002; 48: 877-883
        • Hong H.
        • Xu Z.M.
        • Pang B.S.
        • Cui L.
        • Wei Y.
        • Guo W.J.
        • Mao Y.L.
        • Yang X.C.
        Effects of simvastain combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia.
        Chin Med Sci J. 2004; 19: 145-149
        • Xydakis A.M.
        • Ballantyne C.M.
        Combination therapy for combined dyslipidemia.
        Am J Cardiol. 2002; 90: 21K-29K