A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT Trial)

Clinical Therapeutics

Volumn 35, Issue 9, 2013, Pages

  Maki, Kevin C ^a   Orloff, David G ^b   Nicholls, Stephen J ^c   Dunbar, Richard L ^d   Roth, Eli M ^e   Curcio, Danielle ^f   Johnson, Judith ^f   Kling, Douglas ^f   Davidson, Michael H ^f  

^a Biofortis Clinical Research   (United States)

^b Medpace Inc ^*  (United States)

^c SOUTH AUSTRALIAN HEALTH AND MEDICAL RESEARCH INSTITUTE   (Australia)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e Sterling Research Group   (United States)

^f Omthera Pharmaceuticals Inc   (United States)

Author keywords

Hypertriglyceridemia; LDL C; Omega 3 fatty acids; Statins; Triglycerides

Indexed keywords

APOLIPOPROTEIN; ARACHIDONIC ACID; ATORVASTATIN; DOCOSAHEXAENOIC ACID; DOCOSAPENTAENOIC ACID; FLUINDOSTATIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ICOSAPENTAENOIC ACID; LOW DENSITY LIPOPROTEIN; MEVINOLIN; OMEGA 3 FATTY ACID; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; TRIACYLGLYCEROL; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL;

ADULT; AGED; ARTICLE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CONNECTIVE TISSUE DISEASE; CONTROLLED STUDY; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG BIOAVAILABILITY; DRUG EFFICACY; FEMALE; GASTROINTESTINAL DISEASE; HUMAN; HYPERTRIGLYCERIDEMIA; INFECTION; INFESTATION; LIPID BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; MEDIASTINUM DISEASE; MUSCULOSKELETAL DISEASE; NAUSEA; NEUROLOGIC DISEASE; OUTCOME ASSESSMENT; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY TRACT DISEASE; SUPPLEMENTATION; THORAX DISEASE;

HYPERTRIGLYCERIDEMIA; LDL-C; OMEGA-3 FATTY ACIDS; STATINS; TRIGLYCERIDES;

AGED; BIOLOGICAL AVAILABILITY; CARDIOVASCULAR DISEASES; CHOLESTEROL, HDL; COMBINED MODALITY THERAPY; DIETARY SUPPLEMENTS; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; FATTY ACIDS, NONESTERIFIED; FATTY ACIDS, OMEGA-3; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERTRIGLYCERIDEMIA; MEDICATION ADHERENCE; MIDDLE AGED; PLANT OILS; RISK FACTORS; TRIGLYCERIDES;

EID: 84884355278     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2013.07.420     Document Type: Article

References (33)

1. Toth P.P., Potter D., Ming E.E. Prevalence of lipid abnormalities in the United States: the National Health and Nutrition Examination Survey 2003-2006. J Clin Lipidol 2012, 6:325-330.
2. 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. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
3. Maki K.C., Bays H.E., Dicklin M.R. Treatment options for the management of hypertriglyceridemia: strategies based on the best-available evidence. J Clin Lipidol 2012, 6:413-426.
4. Davidson M.H., Stein E.A., Bays H.E., et al. 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.
5. Bays H.E., McKenney J., Maki K.C., et al. 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.
6. Ballantyne C.M., Bays H.E., Kastelein J.J., et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol 2012, 110:984-992.
7. El Boustani S., Colette C., Monnier L., et al. Enteral absorption in man of eicosapentaenoic acid in different chemical forms. Lipids 1987, 22:711-714.
8. Hazra A., Tripathi S.K., Ghosh A. Pharmacology and therapeutic potential of the n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oils. Indian J Pharmacol 1999, 31:247-264.
9. Lawson L.D., Hughes B.G. Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters. Biochem Biophys Res Commun 1988, 152:328-335.
10. Lawson L.D., Hughes B.G. Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal. Biochem Biophys Res Commun 1988, 156:960-963.
11. Davidson M.H., Johnson J., Rooney M.W., et al. A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova compared to Lovaza in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol 2012, 6:573-584.
12. Kastelein JJP, Maki KC, Susekov A, et al. Dose response of a novel free-fatty acid formulation of omega-3 for the management of dyslipidemia in patients with severe hypertriglyceridemia-EpanoVa fOr Lowering Very High TriglycErides (The EVOLVE Trial). Abstract presented at: American Heart Association Scientific Sessions; November 6, 2012; Los Angeles, Calif. Abstract APS.202.04.
13. Maki K.C., McKenney J.M., Reeves M.S., et al. Effects of adding prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia. Am J Cardiol 2008, 102:429-433.
14. Davidson M.H., Rooney M.W., Drucker J., et al. LCP-AtorFen Investigators. Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study. Clin Ther 2009, 31:2824-2838.
15. Keech A., Simes R.J., Barter P., et al. 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.
16. Davidson M.H., Armani A., McKenney J.M., Jacobson T.A. Safety considerations with fibrate therapy. Am J Cardiol 2007, 19:3C-18C.
17. Maki K.C., Dicklin M.R., Davidson M.H., et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Baseline lipoprotein lipids and low-density lipoprotein cholesterol response to prescription omega-3 acid ethyl ester added to simvastatin therapy. Am J Cardiol 2010, 105:1409-1412.
18. Nordøy A., Bonaa K.H., Nilsen H., et al. 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.
19. Durrington P., Bhatnagar D., Mackness M., et al. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin-treated patients with coronary heart disease and persisting hypertriglyceridemia. Heart 2001, 85:544-548.
20. Tatsuno I., Saito Y., Kudou K., Ootake J. Efficacy and safety of TAK-085 compared with eicosapentaenoic acid in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification. The omega-3 fatty acids randomized double-blind (ORD) study. J Clin Lipidol 2013, 7:199-207.
21. Chan D.C., Watts G.F., Barrett P.H., et al. Regulatory effects of HMG CoA reductase inhibitors and fish oils on apolipoprotein B-100 kinetics in insulin-resistant obese male subjects with dyslipidemia. Diabetes 2002, 51:2377-2386.
22. Chan D.C., Watts G.F., Mori T.A., et al. Randomized controlled trial of the effect of n-3 fatty acid supplementation on the metabolism of apolipoprotein B-100 and chylomicron remnants in men with visceral obesity. Am J Clin Nutr 2003, 77:300-307.
23. Albert C.M., Campos H., Stampfer M.J., et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 2002, 346:1113-1118.
24. Itakura H., Yokoyama M., Matsuzaki M., et al. for the JELIS Investigators. Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb 2011, 18:99-107.
25. Australian Government. Department of Health and Ageing. Therapeutic Goods Administration. Australian Public Assessment Report for omega-3 acid ethyl esters 90. Abbott Products Pty Ltd (formerly Solvay Pharmaceuticals Pty Ltd). PM-2008-3043-3. October 2010. Accessed August 9, 2013. http://www.tga.gov.au/pdf/auspar/auspar-omacor.pdf.
26. Robinson J.G., Stone N.J. Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids. Am J Cardiol 2006, 98:39i-49i.
27. Jump D.B., Depner C.M., Tripathy S. Omega-3 fatty acid supplementation and cardiovascular disease: Thematic Review Series: new lipid and lipoproteins targets for the treatment of cardiometabolic diseases. J Lipid Res 2012, 53:2525-2545.
28. Nakamura N., Hamazaki T., Jokaji H., et al. Effect of HMG-CoA reductase inhibitors on plasma polyunsaturated fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1998, 28:192-195.
29. Kris-Etherton P.M., Harris W.S., Appel L.J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002, 106:2747-2757. American Heart Association. Nutrition Committee.
30. Grundy S.M., Cleeman J.I., Merz C.N., et al. Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol 2004, 44:720-732.
31. Harris W.S., Lu G., Rambjor G.S., et al. Influence of n-3 fatty acid supplementation on the endogenous activities of plasma lipases. Am J Clin Nutr 1997, 66:254-260.
32. Maki K.C., Van Elswyk M.E., McCarthy D., et al. Lipid responses to a dietary docosahexaenoic acid supplement in men and women with below average levels of high density lipoprotein cholesterol. J Am Coll Nutr 2005, 24:189-199.
33. Lichtenstein A.H., Ausman L.M., Carrasco W., et al. Effects of canola, corn, and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a National Cholesterol Education Program Step 2 diet. Arterioscler Thromb 1993, 13:1533-1542.