Omega-3 fatty acid therapy for cardiovascular disease: justified or not?
Journal
Current opinion in cardiology
ISSN: 1531-7080
Titre abrégé: Curr Opin Cardiol
Pays: United States
ID NLM: 8608087
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
pubmed:
16
5
2020
medline:
25
9
2020
entrez:
16
5
2020
Statut:
ppublish
Résumé
To discuss the current evidence regarding the relationship between omega-3 fatty acid intake and atherosclerotic cardiovascular disease (ASCVD) risk. Combined results from randomized controlled trials using low-dosage (≤1.8 g/day of ethyl esters) eicosapentaenoic acid (EPA) or EPA + docosahexaenoic acid (DHA) suggest a small benefit for reducing coronary heart disease risk. The Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) that administered 4 g/day icosapent ethyl (IPE) to individuals on statin at high or very high ASCVD risk with elevated triglycerides demonstrated a 25% relative risk reduction in the composite primary endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization and unstable angina) for IPE vs. placebo, and a lower hazard for all prespecified individual endpoints other than total mortality. Several national organizations have recommended IPE for ASCVD risk reduction in populations aligning with REDUCE-IT; the Food and Drug Administration has approved IPE for ASCVD risk reduction. However, the Outcomes Study to Assess Statin Residual Risk Reduction with Epanova (EPA + DHA carboxylic acids) in High Cardiovascular Risk Patients with Hypertriglyceridemia was recently stopped for futility. At present, the best available evidence for a role of omega-3 fatty acids in ASCVD risk reduction is for 4 g/day of IPE, as an adjunct to statin therapy, for patients with ASCVD or diabetes mellitus and elevated triglycerides.
Identifiants
pubmed: 32412960
doi: 10.1097/HCO.0000000000000741
pii: 00001573-202007000-00018
doi:
Substances chimiques
Fatty Acids, Omega-3
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
417-422Références
Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996; 3:213–219.
Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007; 298:299–308.
Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 2008; 300:2142–2152.
Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG, Tybjaerg-Hansen A. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med 2014; 371:32–41.
Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014; 384:626–635.
Rosenson RS, Davidson MH, Hirsh BJ, et al. Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease. J Am Coll Cardiol 2014; 64:2525–2540.
Jorgensen AB, Frikke-Schmidt R, West AS, et al. Genetically elevated nonfasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013; 34:1826–1833.
Stitziel NO, Stirrups KE, Masca NG, et al. Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators. Coding Variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease. N Engl J Med 2016; 374:1134–1144.
Dewey FE, Gusarova V, Dunbar RL, et al. Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease. N Engl J Med 2017; 377:211–221.
Sarwar N, Sandhu MS, Ricketts SL, et al. Triglyceride Coronary Disease Genetics Constorium and Emerging Risk Factors Collaboration. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 2010; 375:1634–1639.
Ference BA, Kastelein JJP, Ray KK, et al. Association of triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants with risk of coronary heart disease. JAMA 2019; 321:364–373.
Ginsberg HN, Elam MB, Lovato LC, et al. ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010; 362:1563–1574.
Boden WE, Probstfield JL, Anderson T, et al. AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011; 365:2255–2267.
Landray MJ, Haynes R, Hopewell JC, et al. HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014; 371:203–212.
Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010; 375:1875–1884.
Sacks FM, Carey VJ, Fruchart JC. Combination lipid therapy in type 2 diabetes. N Engl J Med 2010; 363:692–694. author reply 4–5.
Lee M, Saver JL, Towfighi A, et al. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis 2011; 217:492–498.
Maki KC, Guyton JR, Orringer CE, et al. Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia. J Clin Lipidol 2016; 10:905–914.
Aung T, Halsey J, Kromhout D, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77917 individuals. JAMA Cardiol 2018; 3:225–234.
Hu Y, Hu FB, Manson JE. Marine omega-3 supplementation and cardiovascular disease: an updated meta-analysis of 13 randomized controlled trials involving 127 477 participants. J Am Heart Assoc 2019; 8:e013543.
de Goede J, Geleijnse JM, Boer JM, et al. Marine (n-3) fatty acids, fish consumption, and the 10-year risk of fatal and nonfatal coronary heart disease in a large population of Dutch adults with low fish intake. J Nutr 2010; 140:1023–1028.
Rizos EC, Ntzani EE, Bika E, et al. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA 2012; 308:1024–1033.
Del Gobbo LC, Imamura F, Aslibekyan S, et al. Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies. JAMA Intern Med 2016; 176:1155–1166.
Alexander DD, Miller PE, Van Elswyk ME, et al. A meta-analysis of randomized controlled trials and prospective cohort studies of eicosapentaenoic and docosahexaenoic long-chain omega-3 fatty acids and coronary heart disease risk. Mayo Clin Proc 2017; 92:15–29.
Bowman L, Mafham M, Wallendszus FK, et al. ASCEND Study Collaborative Group. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med 2018; 379:1540–1550.
Manson JE, Cook NR, Lee IM, et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med 2019; 380:23–32.
Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007; 369:1090–1098.
Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019; 380:11–22.
Itakura H, Yokoyama M, Matsuzaki M, et al. Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb 2011; 18:99–107.
Papanikolaou Y, Brooks J, Reider C, Fulgoni VL 3rd. U. S. adults are not meeting recommended levels for fish and omega-3 fatty acid intake: results of an analysis using observational data from NHANES. Nutr J 2014; 13:31.
Otsuka R, Tange C, Nishita Y, et al. Fish and meat intake, serum eicosapentaenoic acid and docosahexaenoic acid levels, and mortality in community-dwelling Japanese older persons. Int J Environ Res Public Health 2019; 16:1806.
Saito Y, Yokoyama M, Origasa H, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 2008; 200:135–140.
Marchioli R, Levantesi G, Maccia A, et al. Antiarrythmic mechanisms of n-3 PUFA and the results of the GISS-Prevenzione Trial. J Membrane Biol 2005; 206:117–128.
Siscovick DS, Barringer TA, Wu JHY, et al. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease. A Science Advisory from the American Heart Association. Circulation 2017; 135:e867–e884.
Tribulova N, Bacova BS, Benova TE, et al. Omega-3 index and antiarrythmic potential of omega-3 PUFAs. Nutrients 2017; 9:1191.
Kowey PR, Reiffel JA, Ellenbogen KA, et al. Efficacy and safety of prescription omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: a randomized controlled trial. JAMA 2010; 304:2363–2372.
Heydari B, Abdullah S, Pottala JV, et al. Effect of omega-3 acid ethyl esters on left ventricular remodeling after acute myocardial infarction: the OMEGA-REMODEL randomized clinical trial. Circulation 2016; 134:378–391.
Morita N, Mandel WJ, Kobayashi Y, Karaguezian HS. Cardiac fibrosis as a determinant of ventricular tachyarrhythmias. J Arrhythm 2014; 30:389–394.
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41:111–188.
Orringer CE, Jacobson TA, Maki KC. National Lipid Association Scientific Statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCVD risk. J Clin Lipidol 2019; 13:860–872.
American Diabetes, Association 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2020. Diabetes Care 2020; 43: (Suppl 1): S111–S134.
Vascepa (icosapent ethyl) capsules prescribing information. Available at https://www.vascepa.com/assets/pdf/Vascepa_PI.pdf. Accessed January 24, 2020.
Helio Cardiology Today. STRENGTH CV outcomes trial of omega-3 fatty acid stopped for futility. Available at https://www.healio.com/cardiology/chd-prevention/news/online/%7B332e8e21-ad86-4562-8969-72affa69ae6b%7D/strength-cv-outcomes-trial-of-omega-3-fatty-acid-stopped-for-futility. Accessed January 24, 2020.
Nicholls SJ, Lincoff AM, Bash D, et al. Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: rationale and design of the STRENGTH trial. Clin Cardiol 2018; 41:1281–1288.
Varbo A, Benn M, Tybjaerg-Hansen A, et al. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61:427–436.
Oscarsson J, Hurt-Camejo E. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review. Lipids Health Dis 2017; 16:149.
Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation 2019; 140:e673–e691.
Marston NA, Giugliano RP, Im K, et al. Association between triglyceride lowering and reduction of cardiovascular risk across multiple lipid-lowering therapeutic classes: a systematic review and meta-regression analysis of randomized controlled trials. Circulation 2019; 140:1308–1317.
Mozaffarian D, Prineas RJ, Stein PK, Siscovick DS. Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans. J Am Coll Cardiol 2006; 48:478–484.
Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 2011; 58:2047–2067.
Wei MY, Jacobson TA. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep 2011; 13:474–483.
Jacobson TA, Glickstein SB, Rowe JD, Soni PN. Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. J Clin Lipidol 2012; 6:5–18.
Mozaffarian D, Wu JH. N-3 fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr 2012; 142:614S–625S.
Asztalos IB, Gleason JA, Sever S, et al. Effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular disease risk factors: a randomized clinical trial. Metabolism 2016; 65:1636–1645.
Bowen KJ, Harris WS, Kris-Etherton PM. Omega-3 fatty acids and cardiovascular disease: are there benefits? Curr Treat Options Cardiovasc Med 2016; 18:69.
Preston Mason R, Jacob RF, Shrivastava S, et al. Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain formation, and normalizes bilayer width in atherosclerotic-like model membranes. Biochim Biophys Acta 2016; 1858:3131–3140.
Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol 2018; 72:330–343.
Goel A, Pothineni NV, Singhal M, et al. Fish, fish oils and cardioprotecion: promise or fish tale? Int J Mol Sci 2018; 19:3703.
Preston Mason R. New insights into mechanisms of action for omega-3 fatty acids in atherothrombotic cardiovascular disease. Curr Atheroscler Rep 2019; 21:2.
Budoff M, Brent Muhlestein J, Le VT, et al. Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200-499 mg/dL) on statin therapy: rationale and design of the EVAPORATE study. Clin Cardiol 2018; 41:13–19.
American College of Cardiology. Latest in Cardiology. Nov 18, 2019. Effect of icosapent ethyl on progresison of coronary atherosclerosis in patients with elevated triglycerides on statin tehrapy – EVAPORATE. Available at https://www.acc.org/latest-in-cardiology/clinical-trials/2019/11/15/17/46/evaporate?promo_creative=/latest-in-cardiology/clinical-trials/2019/11/15/17/46/evaporate&promo_position=image_slider_1&promo_id=Latest-in-Cardiology&promo_name=featured_content. Accessed on January 24, 2020.