Why Have Antioxidants Failed in Clinical Trials?

American Journal of Cardiology

Volumn 101, Issue 10 SUPPL., 2008, Pages

  Steinhubl, Steven R ^a  

^a GEISINGER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; ALPHA TOCOPHEROL; ANTIOXIDANT; GLYCERYL TRINITRATE; STREPTOKINASE;

ARTICLE; ATHEROSCLEROSIS; CLINICAL TRIAL; DRUG EFFECT; HEART INFARCTION; HUMAN; INFLAMMATION; OXIDATIVE STRESS; PRIORITY JOURNAL; VITAMIN SUPPLEMENTATION;

ANTIOXIDANTS; CLINICAL TRIALS AS TOPIC; CORONARY ARTERY DISEASE; EVIDENCE-BASED MEDICINE; HUMANS; OXIDATIVE STRESS; RISK FACTORS; TREATMENT FAILURE;

EID: 43049180323     PISSN: 00029149     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.amjcard.2008.02.003     Document Type: Article

References (33)

1. Dzau V.J., Antman E.M., Black H.R., Hayes D.L., Manson J.E., Plutzky J., Popma J.J., and Stevenson W. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes. Part II: clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation 114 (2006) 2871-2891
2. Verlangieri A.J., Kapeghian J.C., el-Dean S., and Bush M. Fruit and vegetable consumption and cardiovascular mortality. Med Hypotheses 16 (1985) 7-15
3. Gey K.F., and Puska P. Plasma vitamins E and A inversely correlated to mortality from ischemic heart disease in cross-cultural epidemiology. Ann N Y Acad Sci 570 (1989) 268-282
4. Rimm E.B., Stampfer M.J., Ascherio A., Giovannucci E., Colditz G.A., and Willett W.C. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 328 (1993) 1450-1456
5. Stampfer M.J., Hennekens C.H., Manson J.E., Colditz G.A., Rosner B., and Willett W.C. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 328 (1993) 1444-1449
6. Knekt P., Reunanen A., Jarvinen R., Seppanen R., Heliovaara M., and Aromaa A. Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol 139 (1994) 1180-1189
7. Todd S., Woodward M., Tunstall-Pedoe H., and Bolton-Smith C. Dietary antioxidant vitamins and fiber in the etiology of cardiovascular disease and all-causes mortality: results from the Scottish Heart Health Study. Am J Epidemiol 150 (1999) 1073-1080
8. Vivekananthan D.P., Penn M.S., Sapp S.K., Hsu A., and Topol E.J. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361 (2003) 2017-2023
9. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330 (1994) 1029-1035
10. Stephens N.G., Parsons A., Schofield P.M., Kelly F., Cheeseman K., and Mitchinson M.J. Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347 (1996) 781-786
11. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 354 (1999) 447-455
12. Hegele R.A. Angiotensin-converting enzyme (ACE) inhibition in the secondary prevention of vascular disease: the Heart Outcomes Prevention Evaluation (HOPE) Trial and its substudies. Curr Atheroscler Rep 2 (2000) 361-362
13. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 360 (2002) 23-33
14. de Gaetano G., and Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet 357 (2001) 89-95
15. Redlich C.A., Chung J.S., Cullen M.R., Blaner W.S., Van Bennekum A.M., and Berglund L. Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET). Atherosclerosis 145 (1999) 425-432
16. Green A., Williams G., Neale R., Hart V., Leslie D., Parsons P., Marks G., Gaffney P., Battistutta D., Frost C., and Nambour Skin Cancer Prevention Trial (NSCP). Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 354 (1999) 723-729
17. Hennekens C.H., Buring J.E., Manson J.E., Stampfer M., Rosner B., Cook N.R., Belanger C., LaMotte F., Gaziano J.M., Ridker P.M., Willett W., and Peto R. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334 (1996) 1145-1149
18. Lee I.-M., Cook N.R., Manson J.E., Buring J.E., and Hennekens C.H. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Womens' Health Study. J Natl Cancer Inst 91 (1999) 2102-2109
19. Bleys J., Miller III E.R., Pastor-Barriuso R., Appel L.J., and Guallar E. Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials. Am J Clin Nutr 84 (2006) 880-887 quiz 954-955
20. Brown B.G., Zhao X.Q., Chait A., Fisher L.D., Cheung M.C., Morse J.S., Dowdy A.A., Marino E.K., Bolson E.L., Alaupovic P., Frohlich J., and Albers J.J. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 345 (2001) 1583-1592
21. Lonn E.M., Yusuf S., Dzavik V., Doris I., Yi Q., Smith S., Moore-Cox A., Bosch J., Riley W.A., Teo K.K., and SECURE Investigators. Effect of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation 103 (2001) 919-925
22. Fang J.C., Kinlay S., Beltrame J., Hikiti H., Wainstein M., Behrendt D., Suh J., Frei B., Mudge G.H., Selwyn A.P., and Ganz P. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet 359 (2002) 1108-1113
23. Hodis H.N., Mack W.J., LaBree L., Mahrer P.R., Sevanian A., Liu C.R., Liu C.H., Hwang J., Selzer R.H., Azen S.P., and VEAPS Research Group. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation 106 (2002) 1453-1459
24. Waters D.D., Alderman E.L., Hsia J., Howard B.V., Cobb F.R., Rogers W.J., Ouyang P., Thompson P., Tardif J.C., Higginson L., et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA 288 (2002) 2432-2440
25. Salonen R.M., Nyyssönen K., Kaikkonen J., Porkkala-Sarataho E., Voutilainen S., Rissanen T.H., Tuomainen T.P., Valkonen V.P., Ristonmaa U., Lakka H.M., et al. Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. Circulation 107 (2003) 947-953
26. Hercberg S., Galan P., Preziosi P., Bertrais S., Mennen L., Malvy D., Roussel A.M., Favier A., and Briançon S. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 164 (2004) 2335-2342
27. Arstall M.A., Yang J., Stafford I., Betts W.H., and Horowitz J.D. N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction: safety and biochemical effects. Circulation 92 (1995) 2855-2862
28. Marenzi G., Assanelli E., Marana I., Lauri G., Campodonico J., Grazi M., De Metrio M., Galli S., Fabbiocchi F., Montorsi P., Veglia F., and Bartorelli A.L. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 354 (2006) 2773-2782
29. Pearson P., Lewis S.A., Britton J., Young I.S., and Fogarty A. The pro-oxidant activity of high-dose vitamin E supplements in vivo. BioDrugs 20 (2006) 271-273
30. Bjelakovic G., Nikolova D., Gluud L.L., Simonetti R.G., and Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297 (2007) 842-857
31. Miller III E.R., Pastor-Barriuso R., Dalal D., Riemersma R.A., Appel L.J., and Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142 (2005) 37-46
32. Serfontein W.J., Ubbink J.B., and de Villiers L.S. Further evidence on the effect of vitamin E on the cholesterol distribution in lipoproteins with special reference to HDL subfractions. Am J Clin Pathol 79 (1983) 604-606
33. Kaliora A.C., Dedoussis G.V., and Schmidt H. Dietary antioxidants in preventing atherogenesis. Atherosclerosis 187 (2006) 1-17