Skip to main content
SpringerLink
Log in

The Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto miocardio (GISSI)-Prevenzione trial on fish oil and vitamin E supplementation in myocardial infarction survivors

  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

A recent large-scale, open-label, randomized, controlled trial in 11,324 myocardial infarction (MI) survivors has shown low-dose fish oil, but not vitamin E, to reduce significantly the cumulative rate of all-cause death, nonfatal MI, and nonfatal stroke. Neither intervention significantly reduced the other primary endpoint, the cumulate rate of cardiovascular death, nonfatal MI, and nonfatal stroke. Analysis of secondary endpoints indicated that the benefits of the 875 mg fish oil capsules containing 850 to 882 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as ethyl esters was in reducing mortality and not in a reduction of nonfatal MI. It was a safe intervention. The internal validity and external validity of the data was examined and the findings placed in clinical perspective. Important questions remain about the benefits of increased plant sources of n-3 polyunsaturated fatty acids (PUFA) for those who cannot obtain or consume fish. Also the benefits of diet versus fish oil supplementation haven’t been determined precisely. Although it seems reasonable to increase sources of n-3 PUFA in the diet for those at high risk of coronary heart disease, current data do not support a policy of promoting fish oil capsules for secondary prevention of coronary heart disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Harris WS: Fish oil and plasma lipid and lipoprotein metabolism in humans: a critical review. J Lipid Res 1989, 30:785–807.

    PubMed  CAS  Google Scholar 

  2. Israel DH, Gorlin R: Fish oils in the prevention of atherosclerosis. J Am Coll Cardiol 1992, 19:174–185.

    Article  PubMed  CAS  Google Scholar 

  3. Stone NJ: Fish consumption, fish oil, lipids, and coronary heart disease. Circulation 1996, 94:2337–2340.

    PubMed  CAS  Google Scholar 

  4. Angerer P, von Schacky C: n-3 Polyunsaturated fatty acids and the cardiovascular system. Curr Opin Lipidol 2000, 11:57–63. An ellent review of current studies.

    Article  PubMed  CAS  Google Scholar 

  5. Baumann KH, Hessel F, Larass I, et al.: Dietary omega-3, omega-6 and omega-9 unsaturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomized volunteer study. Arterioscler Thromb Vasc Biol 1999, 19:59–66.

    PubMed  CAS  Google Scholar 

  6. Chin JP, Dart AM: HBPRCA Astra Award. Therapeutic restoration of endothelial function in hypercholesterolaemic subjects: effect of fish oils. Clin Exp Pharmacol Physiol Dev 1994, 21:749–755.

    CAS  Google Scholar 

  7. Morris MC, Sacks F, Rosner B: Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation 1993, 88:523–533.

    PubMed  CAS  Google Scholar 

  8. Sanders TAB, Oakley FR, Miller GJ, et al.: Influence of n-6 versus n-3 Polyunsaturated Fatty Acids in Diets Low in Saturated Fatty Acids on Plasma Lipoproteins and Hemostatic Factors. Arterioscler Thromb Vasc Biol 1997, 17:3449–3460.

    PubMed  CAS  Google Scholar 

  9. Leaf A, Weber PC: Cardiovascular effects of N-3 fatty acids. N Engl J Med 1985, 312:1205–1209.

    Article  Google Scholar 

  10. Dyerberg J, Bung HO: Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 1979, 2:433–435.

    Article  PubMed  CAS  Google Scholar 

  11. Billman GE, Hallaq H, Leaf A: Prevention of ischemia-induced ventricular fibrillation by n-3 fatty acids. Proc Natl Acad Sci U S A 1994, 91:4427–4430.

    Article  PubMed  CAS  Google Scholar 

  12. Kang JX, Leaf A: Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids Am J Clin Nutr 2000, 71:202–207. Detailed review of basis for using PUFA to deter ischemia induced fatal cardiac arrhythmias.

    Google Scholar 

  13. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico: Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999, 354:447–455. The authors demonstrated a significant effect of the low-dose fish oil capsules on one of two primary combined endpoints. Secondary analyses suggested that most of the benefit was due to a decrease in fatal events. Vitamin E had no effect on the primary endpoints in this trial.

    Article  Google Scholar 

  14. Burr ML, Fehily AM, Gilbert JF, et al.: Effects of changes in fat, fish, and fibre intakes on death and myocardial infarction: diet and reinfarction trial [DART]. Lancet 1989, 2:757–761.

    Article  PubMed  CAS  Google Scholar 

  15. Ness AR, Whitley E, Burr ML, et al.: The long-term effect of advice to eat more fish on blood pressure in men with coronary disease: results from the diet. J Hum Hypertens 1999, 13:729–733.

    Article  PubMed  CAS  Google Scholar 

  16. Singh RB, Niaz MA, Sharma JP, et al.: Randomized, doubleblind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival-4 and reinfarction trial. Cardiovasc Drugs Ther 1997, 11:485–491.

    Article  PubMed  CAS  Google Scholar 

  17. Siscovick DS, Raghunathan TE, King I, et al.: Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA 1995, 274:1363–1367.

    Article  PubMed  CAS  Google Scholar 

  18. Christensen JH, Gustenhoff P, Korup E, et al.: Effect of fish oil on heart rate variability in survivors of myocardial infarction: a double blind randomised controlled trial. Br Med J 1996, 312:677–678.

    CAS  Google Scholar 

  19. Christensen JH, Gustenhoff P, Korup E, et al.: Fish consumption, n-3 fatty acids in cell membranes, and heart rate variability in survivors of myocardial infarction with left ventricular dysfunction. Am J Cardiol 1997, 79:1671–1673.

    Article  Google Scholar 

  20. Christensen JH, Aarøe J, Knudsen N, et al.: Heart rate variability and n-3 fatty acids in patients with chronic renal failure-a pilot study. Clin Nephrol 1998, 49:102–106.

    PubMed  CAS  Google Scholar 

  21. Hartikainen JK, Malik M, Staunton A, et al.: Distinction between arrhythmic and nonarrhythmic death after acute myocardial infarction based on heart rate variability, signal-averaged electrocardiogram, ventricular arrhythmias and left ventricular ejection fraction. J Am Coll Cardiol 1996, 28:296–304.

    PubMed  CAS  Google Scholar 

  22. Sacks FM, Stone PH, Gibson CM, et al., for the HARP Research Group: Controlled trial of fish oil for regression of human coronary atherosclerosis. J Am Coll Cardiol 1995, 25:1492–1498.

    Article  PubMed  CAS  Google Scholar 

  23. von Schacky C, Angerer P, Kothny W, et al.: The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999, 130:554–562.

    Google Scholar 

  24. Bairati I, Roy, Meyer F: Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty. Circulation 1992, 85:950–956.

    PubMed  CAS  Google Scholar 

  25. Leaf A, Jorgensen MB, Jacobs AK, et al.: Do fish oils prevent restenosis after coronary angioplasty? Circulation 1994, 90:2248–2257.

    PubMed  CAS  Google Scholar 

  26. Johansen O, Brekke M, Seljeflot I, et al.: N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial. J Am Coll Cardiol 1999, 33:1619–1626.

    Article  PubMed  CAS  Google Scholar 

  27. Connor WE: Alpha-linolenic acid in health and disease. Am J Clin Nutr 1999, 69:827–828. Superb information on alpha-linolenic acid with excellent tables.

    PubMed  CAS  Google Scholar 

  28. Salem N, Wegher B, Mena P, Uauy RD: Arachidonic acid and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc Natl Acad Sci USA 1996, 93:49–54.

    Article  PubMed  CAS  Google Scholar 

  29. De-Lorgeril M, Renaud S, Mamelle N, et al.: Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994, 343:1454–1459.

    Article  PubMed  CAS  Google Scholar 

  30. de Lorgeril M, Salen P, Martin J-L, et al.: Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999, 99:779–785.

    PubMed  Google Scholar 

  31. Schaefer EJ, Lichtenstein AH, Lamon-Fava S, et al.: Effects of National Cholesterol Education Program Step 2 diets relatively high or relatively low in fish-derived fatty acids on plasma lipoproteins in middle-aged and elderly subjects. Am J Clin Nutr 1996, 63:234–241.

    PubMed  CAS  Google Scholar 

  32. Svensson B-G, Nilsson A, Hansson M, et al.: Exposure to dioxins and dibenzoflurans through the consumption of fish. N Engl J Med 1991, 324:8–12.

    Article  PubMed  CAS  Google Scholar 

  33. Salonen JT, Seppanen K, Nyysonen K, et al.: Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. Circulation 1995, 91:645–655.

    PubMed  CAS  Google Scholar 

  34. Schectman G, Kaul S, Cherayil GD, et al.: Can the hypotriglyceridemic effect of fish oil concentrate be sustained? Ann Int Med 1989, 110:346–352.

    PubMed  CAS  Google Scholar 

  35. Glauber H, Wallace P, Griver K, Brechtel G: Adverse metabolic effect of omega-3 fatty acids in non-insulin dependent diabetes mellitus. Ann Intern Med 1988, 108:663–668.

    PubMed  CAS  Google Scholar 

  36. Harris WS, Silveira S, Dujovne CA: The combined effects of N-3 fatty acids and aspirin on hemostatic parameters in man. Thromb Res 1990, 57:517–526.

    Article  PubMed  CAS  Google Scholar 

  37. Dyerberg J, Bang HO: Lipid metabolism, atherogenesis, and haemostasis in Eskimos: the role of the prostaglandin-3 family. Haemostasis 1979, 8:227–233.

    PubMed  CAS  Google Scholar 

  38. Kromhout D, Bosschieter EB, de Lezenne Coulander C: The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985, 312:1205–1209.

    Article  PubMed  CAS  Google Scholar 

  39. Kromhout D, Feskens EJ, Bowles CH: The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Int J Epidemiol 1995, 24:340–345.

    Article  PubMed  CAS  Google Scholar 

  40. Pauletto P, Puato M, Caroli MG, et al.: Blood pressure and atherogenic lipoprotein profiles of fish-diet and vegetarian villagers in Tanzania: the Lugalawa study. Lancet 1996, 348:784–788.

    Article  PubMed  CAS  Google Scholar 

  41. Daviglus ML, Stamler J, Orencia AJ, et al.: Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med 1997, 336:1046–1053.

    Article  PubMed  CAS  Google Scholar 

  42. Albert CM, Hennekens CH, O’Donnell CJ, et al.: Fish consumption and risk of sudden cardiac death. JAMA 1998, 279:23–28.

    Article  PubMed  CAS  Google Scholar 

  43. Ascherio A, Rimm EB, Stampfer MJ, et al.: Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 1995, 332:977–982.

    Article  PubMed  CAS  Google Scholar 

  44. Guallar E, Hennekens CH, Sacks FM, et al.: A prospective study of plasma fish oil levels and incidence of myocardial infarction in US male physicians. J Am Coll Cardiol 1995, 25:387–394.

    Article  PubMed  CAS  Google Scholar 

  45. Pietinen P, Ascherio A, Korhonen P, et al.: Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol. 1997, 145:876–887.

    PubMed  CAS  Google Scholar 

  46. Hu FB, Stampfer MJ, Manson JE, et al.: Dietary intake of a-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr 1999, 69:890–897.

    PubMed  CAS  Google Scholar 

  47. Harris WS, Ginsberg HN, Arunakul N, et al.: Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk 1997, 4:385–391.

    Article  PubMed  CAS  Google Scholar 

  48. Axelrod L, Camuso J, Williams E, et al.: Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study. Diabetes Care 1994, 17:37–44.

    Article  PubMed  CAS  Google Scholar 

  49. Grundy SM, Bazzarre T, Cleeman J, et al.: Prevention Conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: medical office assessment: Writing Group I. Circulation 2000, 101:e3. Important conference focusing on the high-risk patient for primary prevention. Sections from all three writing groups are worth reading.

    PubMed  CAS  Google Scholar 

  50. O’Keefe JH, Harris WS: From Inuit to implementation. Omega-3 Fatty Acids Come of Age. Mayo Clinic Proc 2000, 75: 607–614.

    Article  CAS  Google Scholar 

  51. Leaf A: Dietary prevention of coronary heart disease: the Lyon Diet Heart Study. Circulation 1999, 99:733–735.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Northwestern University School of Medicine, 211 E. Chicago Avenue, STE 1050, 60611, Chicago, Illinois, USA

    Neil J. Stone MD

Authors
  1. Neil J. Stone MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stone, N.J. The Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto miocardio (GISSI)-Prevenzione trial on fish oil and vitamin E supplementation in myocardial infarction survivors. Curr Cardiol Rep 2, 445–451 (2000). https://doi.org/10.1007/s11886-000-0059-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-000-0059-5

Keywords

Search

Navigation