Circulation. 2002;105:1897-1903
Published online before print April 8, 2002, doi: 10.1161/01.CIR.0000014682.14181.F2
Published online before print April 8, 2002, doi: 10.1161/01.CIR.0000014682.14181.F2
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(Circulation. 2002;105:1897.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Early Protection Against Sudden Death by n-3 Polyunsaturated Fatty Acids After Myocardial Infarction
Time-Course Analysis of the Results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione
From the Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti (R.M., F.B., E.B., R.D.M., R.M.M., G.T.); Ospedale Civile, Caserta (C.C.); Ospedale Civile, Lanciano (D.D.G., L.M., G.M., C.T.); Department of Cardiovascular Research, Istituto Mario Negri, Milano (M.G.F.); Ospedale Cervello, Palermo (E.G.); Ospedale Civile, Vasto (G.L.); Centro Studi ANMCO, Firenze (A.P.M.); Ospedale Civile, Napoli (N.M.); Ospedale S. Maria degli Angeli, Pordenone (G.L.N.); Ospedale San Filippo Neri, Roma (M.S.); Ospedale Civile, Presidio di Riabilitazione, Passirana di Rho, Milano (C.S.); and IRCCS Policlinico San Matteo, Pavia (L.T.); Ospedale San Gerardo Nuovo, Monza (F.V.), Italy.
Correspondence to Roberto Marchioli, MD, GISSI-Prevenzione Secretariat, Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro, Italy. E-mail marchioli{at}negrisud.it
Background— Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction.
Methods and Results— In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths.
Conclusions— The early effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.
Key Words: fatty acids • death, sudden • trials • coronary disease • antiarrhythmia agents
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W. S. Harris, S. A. Sands, S. L. Windsor, H. A. Ali, T. L. Stevens, A. Magalski, C. B. Porter, and A. M. Borkon Omega-3 Fatty Acids in Cardiac Biopsies From Heart Transplantation Patients: Correlation With Erythrocytes and Response to Supplementation Circulation, September 21, 2004; 110(12): 1645 - 1649. [Abstract] [Full Text] [PDF]
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L. Tavazzi, G. Tognoni, M. G. Franzosi, R. Latini, A. P. Maggioni, R. Marchioli, G. L. Nicolosi, M. Porcu, and on behalf of the GISSI-HF investigators Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure Eur J Heart Fail, August 1, 2004; 6(5): 635 - 641. [Abstract] [Full Text] [PDF]
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M. E. Surette, M. Edens, F. H. Chilton, and K. M. Tramposch Dietary Echium Oil Increases Plasma and Neutrophil Long-Chain (n-3) Fatty Acids and Lowers Serum Triacylglycerols in Hypertriglyceridemic Humans J. Nutr., June 1, 2004; 134(6): 1406 - 1411. [Abstract] [Full Text] [PDF]
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 J. H. Dwyer, H. Allayee, K. M. Dwyer, J. Fan, H. Wu, R. Mar, A. J. Lusis, and M. Mehrabian Arachidonate 5-Lipoxygenase Promoter Genotype, Dietary Arachidonic Acid, and Atherosclerosis N. Engl. J. Med., January 1, 2004; 350(1): 29 - 37. [Abstract] [Full Text] [PDF]
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J. G.F. Cleland, N. Freemantle, G. Kaye, M. Nasir, P. Velavan, K. Lalukota, T. Mudawi, R. Shelton, A. L. Clark, and A. P. Coletta Clinical trials update from the American Heart Association meeting: {Omega}-3 fatty acids and arrhythmia risk in patients with an implantable defibrillator, ACTIV in CHF, VALIANT, the Hanover autologous bone marrow transplantation study, SPORTIF V, ORBIT and PAD and DEFINITE Eur J Heart Fail, January 1, 2004; 6(1): 109 - 115. [Abstract] [Full Text] [PDF]
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J. H. O'Keefe Jr and L. Cordain Cardiovascular Disease Resulting From a Diet and Lifestyle at Odds With Our Paleolithic Genome: How to Become a 21st-Century Hunter-Gatherer Mayo Clin. Proc., January 1, 2004; 79(1): 101 - 108. [Abstract] [PDF]
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W. S. Harris, J. H. O'Keefe Jr, and S. M. Grundy Preventive Use of N-3 Fatty Acids * Response Circulation, November 11, 2003; 108 (19): e139 - e139. [Full Text] [PDF]
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 K. W. Lee and G. Y. H. Lip Effects of Lifestyle on Hemostasis, Fibrinolysis, and Platelet Reactivity: A Systematic Review Arch Intern Med, October 27, 2003; 163(19): 2368 - 2392. [Abstract] [Full Text] [PDF]
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J. Dallongeville, J. Yarnell, P. Ducimetiere, D. Arveiler, J. Ferrieres, M. Montaye, G. Luc, A. Evans, A. Bingham, B. Hass, et al. Fish Consumption Is Associated With Lower Heart Rates Circulation, August 19, 2003; 108(7): 820 - 825. [Abstract] [Full Text] [PDF]
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K. P. Anderson Lipid-lowering therapy for prevention of ventricular tachyarrhythmias J. Am. Coll. Cardiol., July 2, 2003; 42(1): 88 - 92. [Full Text] [PDF]
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A. T Erkkila, S. Lehto, K. Pyorala, and M. I. Uusitupa n-3 Fatty acids and 5-y risks of death and cardiovascular disease events in patients with coronary artery disease Am. J. Clinical Nutrition, July 1, 2003; 78(1): 65 - 71. [Abstract] [Full Text] [PDF]
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K.W. Lee and G.Y.H. Lip The role of omega-3 fatty acids in the secondary prevention of cardiovascular disease QJM, July 1, 2003; 96(7): 465 - 480. [Abstract] [Full Text] [PDF]
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D. S. Siscovick, R. N. Lemaitre, and D. Mozaffarian The Fish Story: A Diet-Heart Hypothesis With Clinical Implications: n-3 Polyunsaturated Fatty Acids, Myocardial Vulnerability, and Sudden Death Circulation, June 3, 2003; 107(21): 2632 - 2634. [Full Text] [PDF]
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A. Leaf, J. X. Kang, Y.-F. Xiao, and G. E. Billman Clinical Prevention of Sudden Cardiac Death by n-3 Polyunsaturated Fatty Acids and Mechanism of Prevention of Arrhythmias by n-3 Fish Oils Circulation, June 3, 2003; 107(21): 2646 - 2652. [Full Text] [PDF]
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 S. Hong, K. Gronert, P. R. Devchand, R.-L. Moussignac, and C. N. Serhan Novel Docosatrienes and 17S-Resolvins Generated from Docosahexaenoic Acid in Murine Brain, Human Blood, and Glial Cells. AUTACOIDS IN ANTI-INFLAMMATION J. Biol. Chem., April 18, 2003; 278(17): 14677 - 14687. [Abstract] [Full Text] [PDF]
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S. M. Grundy N-3 Fatty Acids: Priority for Post-Myocardial Infarction Clinical Trials Circulation, April 15, 2003; 107(14): 1834 - 1836. [Full Text] [PDF]
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F. B. Hu, E. Cho, K. M. Rexrode, C. M. Albert, and J. E. Manson Fish and Long-Chain {omega}-3 Fatty Acid Intake and Risk of Coronary Heart Disease and Total Mortality in Diabetic Women Circulation, April 15, 2003; 107(14): 1852 - 1857. [Abstract] [Full Text] [PDF]
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 O. Ziouzenkova, S. Perrey, L. Asatryan, J. Hwang, K. L. MacNaul, D. E. Moller, D. J. Rader, A. Sevanian, R. Zechner, G. Hoefler, et al. Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase PNAS, March 4, 2003; 100(5): 2730 - 2735. [Abstract] [Full Text] [PDF]
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F. Grodstein, T. B. Clarkson, and J. E. Manson Understanding the Divergent Data on Postmenopausal Hormone Therapy N. Engl. J. Med., February 13, 2003; 348(7): 645 - 650. [Full Text] [PDF]
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W. S Harris n-3 Long-chain polyunsaturated fatty acids reduce risk of coronary heart disease death: extending the evidence to the elderly Am. J. Clinical Nutrition, February 1, 2003; 77(2): 279 - 280. [Full Text] [PDF]
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R. N Lemaitre, I. B King, D. Mozaffarian, L. H Kuller, R. P Tracy, and D. S Siscovick n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study Am. J. Clinical Nutrition, February 1, 2003; 77(2): 319 - 325. [Abstract] [Full Text] [PDF]
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P. M. Kris-Etherton, W. S. Harris, L. J. Appel, and for the Nutrition Committee Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): e20 - 30. [Full Text] [PDF]
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 OMEGA-3 FATTY ACIDS LINKED WITH LOWER SUDDEN DEATH AND CHD RISKS Journal Watch Cardiology, January 1, 2003; 2003(101): 5 - 5. [Full Text]
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F. B. Hu and W. C. Willett Optimal Diets for Prevention of Coronary Heart Disease JAMA, November 27, 2002; 288(20): 2569 - 2578. [Abstract] [Full Text] [PDF]
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P. M. Kris-Etherton, W. S. Harris, L. J. Appel, and for the Nutrition Committee Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease Circulation, November 19, 2002; 106(21): 2747 - 2757. [Full Text] [PDF]
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 C. N. Serhan, S. Hong, K. Gronert, S. P. Colgan, P. R. Devchand, G. Mirick, and R.-L. Moussignac Resolvins: A Family of Bioactive Products of Omega-3 Fatty Acid Transformation Circuits Initiated by Aspirin Treatment that Counter Proinflammation Signals J. Exp. Med., October 21, 2002; 196(8): 1025 - 1037. [Abstract] [Full Text] [PDF]
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A. Geelen, I. A. Brouwer, P. L. Zock, J. A. Kors, C. A. Swenne, M. B. Katan, and E. G. Schouten (n-3) Fatty Acids Do Not Affect Electrocardiographic Characteristics of Healthy Men and Women J. Nutr., October 1, 2002; 132(10): 3051 - 3054. [Abstract] [Full Text] [PDF]
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Omega-3 Fatty Acids Linked with Lower Sudden Death and CHD Risks Journal Watch Cardiology, May 31, 2002; 2002(531): 1 - 1. [Full Text]
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A. Leaf On the Reanalysis of the GISSI-Prevenzione Circulation, April 23, 2002; 105(16): 1874 - 1875. [Full Text] [PDF]
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