Probucol and Multivitamins in the Prevention of Restenosis after Coronary Angioplasty
Abstract
BACKGROUND: Oxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Antioxidants may counter oxidative stress and modify neointimal formation and vascular remodeling. Experimental data and small clinical studies have suggested that antioxidants may prevent restenosis after angioplasty. In a double-blind, randomized trial, we studied whether drugs with antioxidant properties decrease the incidence and severity of restenosis after angioplasty. METHODS: One month before angioplasty, 317 patients were randomly assigned to receive one of four treatments: placebo, probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice daily. Patients were treated for four weeks before and six months after angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according to their treatment assignments. Base-line and follow-up angiograms were interpreted by blinded investigators using a quantitative approach. RESULTS: The mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12 +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the placebo group (P = 0.006 for those receiving vs. those not receiving probucol, and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis rates per segment were 20.7 percent in the probucol group, 28.9 percent in the combined-treatment group, 40.3 percent in the multivitamin group, and 38.9 percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6 percent, respectively (P = 0.009 for probucol vs. no probucol). CONCLUSIONS: The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
LDL oxidation is an important aspect of the pathogenic mechanism of atherosclerosis.
“From the viewpoint of cell biology672, 673), immunohistology674, 675) and other factors, it has become clear that LDL oxidation is an important aspect of the pathogenic mechanism of atherosclerosis.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [674]
Cites
Longitudinal data analysis using generalized linear models
LIANG, K.-Y., & ZEGER, S. L. (1986) · Biometrika · doi:10.1093/biomet/73.1.13 · Cited by 18,550 · see citing works
Epstein, F. H., Steinberg, D. I., Parthasarathy, S., Carew, T. E., Khoo, J. C., & Witztum, J. L. (1989) · New England Journal of Medicine · doi:10.1056/nejm198904063201407 · Cited by 6,425 · see citing works
β-Carotene: an Unusual Type of Lipid Antioxidant
Burton, G. W., & Ingold, K. U. (1984) · Science · doi:10.1126/science.6710156 · Cited by 2,150 · see citing works
Book ReviewAmbulatory Pediatric Care
Steinberg, J. B. (1989) · New England Journal of Medicine · doi:10.1056/nejm198901053200122 · Cited by 2,121 · see citing works
Group sequential methods in the design and analysis of clinical trials
POCOCK, S. J. (1977) · Biometrika · doi:10.1093/biomet/64.2.191 · Cited by 1,831 · see citing works
Langille, B. L., & O'Donnell, F. E. (1986) · Science · doi:10.1126/science.3941904 · Cited by 1,124 · see citing works
Anderson, T. J., Meredith, I. T., Yeung, A. C., Frei, B. B., Selwyn, A. P., & Ganz, P. (1995) · New England Journal of Medicine · doi:10.1056/nejm199502233320802 · Cited by 1,108 · see citing works
Kugiyama, K., Kerns, S. A., Morrisett, J. D., Roberts, R., & Henry, P. D. (1990) · Nature · doi:10.1038/344160a0 · Cited by 858 · see citing works
Schwartz, L., Bourassa, M. G., Lespérance, J., Aldridge, H. E., Kazim, F., Salvatori, V. A., Henderson, M. A., Bonan, R., & David, P. R. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806303182603 · Cited by 692 · see citing works
Self-citationGalis, Z. S., Muszynski, M., Sukhova, G. K., SIMON‐MORRISSEY, E., Unemori, E., Lark, M. W., Amento, E. P., & Libby, P. (1994) · Circulation Research · doi:10.1161/01.res.75.1.181 · Cited by 646 · see citing works
The Dietary History as a Tool in Research1
BURKE, B. S. (1947) · Journal of the American Dietetic Association · doi:10.1016/s0002-8223(21)43949-0 · Cited by 625 · see citing works
Probucol inhibits oxidative modification of low density lipoprotein.
Parthasarathy, S., Young, S. G., Witztum, J. L., Pittman, R. C., & Steinberg, D. H. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112349 · Cited by 620 · see citing works
Goodman, D. S., Hulley, S. B., Clark, L. T., Davis, C. E., Fuster, V., LaRosa, J. C., Oberman, A., Schaefer, E. J., Steinberg, D., Brown, W. V., et al. (1988) · Archives of Internal Medicine · doi:10.1001/archinte.148.1.36 · Cited by 529 · see citing works
Vitamin E as an in Vitro and in Vivo Antioxidanta
Burton, G. W., & Ingold, K. U. (1989) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1989.tb14904.x · Cited by 449 · see citing works
Percutaneous Transluminal Coronary Angioplasty
Landau, C., Lange, R. A., & Hillis, L. D. (1994) · New England Journal of Medicine · doi:10.1056/nejm199404073301407 · Cited by 449 · see citing works
SGalis, Z., MMuszynski, KSukhova, G., ESimon-Morrissey, NUnemori, E., WLark, M., EAmento, & PLibby (1994) · Circulation Research · Cited by 402 · see citing works
Free Radicals in Medicine. I. Chemical Nature and Biologic Reactions
Southorn, P. A., & Powis, G. (1988) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(12)64861-7 · Cited by 391 · see citing works
Recycling of vitamin E in human low density lipoproteins.
Kagan, V. E., Serbinova, E. A., Forte, T. M., Scita, G., & Packer, L. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41529-9 · Cited by 322 · see citing works
Jialal, I., & Grundy, S. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41515-9 · Cited by 296 · see citing works
Weintraub, W. S., Boccuzzi, S., Klein, J., Kosinski, A. S., King, S. B., Ivanhoe, R., Cedarholm, J. C., Stillabower, M., Talley, J., Demaio, S., et al. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411173312002 · Cited by 281 · see citing works
Extracellular matrix remodeling after balloon angioplasty injury in a rabbit model of restenosis.
Strauss, B. H., Chisholm, R. J., Keeley, F. W., et al. (1994) · Circulation Research · doi:10.1161/01.res.75.4.650 · Cited by 275 · see citing works
Dietary antioxidants preserve endothelium-dependent vessel relaxation in cholesterol-fed rabbits.
Keaney, J. F., Gaziano, J. M., Xu, A., Frei, B. B., Curran-Celentano, J., Shwaery, G. T., Loscalzo, J., & Vita, J. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.24.11880 · Cited by 198 · see citing works
Currier, J. W., & Faxon, D. P. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)98445-j · Cited by 181 · see citing works
Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits.
Shaish, A., Daugherty, A., O’Sullivan, F., Schonfeld, G., & Heinecke, J. W. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118256 · Cited by 174 · see citing works
Schneider, J. E., Berk, B. C., Gravanis, M. B., Santoian, E. C., Cipolla, G. D., Tarazona, N., Lassegue, B. P., & King, S. B. (1993) · Circulation · doi:10.1161/01.cir.88.2.628 · Cited by 149 · see citing works
Combination of Vitamins C and E Alters the Response to Coronary Balloon Injury in the Pig
Nunes, G. L., Sgoutas, D. S., Redden, R. A., Sigman, S. R., Gravanis, M. B., King, S. B., & Berk, B. C. (1995) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.15.1.156 · Cited by 141 · see citing works
Ferns, G. A., Förster, L., Stewart‐Lee, A. L., et al. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.23.11312 · Cited by 128 · see citing works
Freyschuss, A., Stiko-Rahm, A., Swedenborg, J., et al. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116326 · Cited by 117 · see citing works
DeMaio, S. J., King, S. B., Lembo, N., Roubin, G. S., Hearn, J. A., Bhagavan, H. N., & Sgoutas, D. S. (1992) · Journal of the American College of Nutrition · doi:10.1080/07315724.1992.10718198 · Cited by 111 · see citing works
Sgoutas, D. S., DeMaio, S. J., King, S. B., Lembo, N., Roubin, G. S., Hearn, J. A., Bhagavan, H. N., & Gruentzig, A. R. (1993) · Springer eBooks · doi:10.1007/978-1-4615-2437-3_45 · Cited by 111 · see citing works
Inhibition by probucol of interleukin 1 secretion and its implication in atherosclerosis
Ku, G., Doherty, N. S., Wolos, J. A., Jackson, R. L., Schmidt, L., & Hendricks, D. (1988) · The American Journal of Cardiology · doi:10.1016/s0002-9149(88)80057-2 · Cited by 97 · see citing works
Superoxide generation during cardiopulmonary bypass: Is there a role for vitamin E?
Cavarocchi, N. C., England, M. D., O’Brien, J. F., et al. (1986) · Journal of Surgical Research · doi:10.1016/0022-4804(86)90093-4 · Cited by 95 · see citing works
Reaven, P. D., Parthasarathy, S., Beltz, W. F., et al. (1992) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.12.3.318 · Cited by 87 · see citing works
Preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty
Watanabe, K., Sekiya, M., Ikeda, S., et al. (1996) · American Heart Journal · doi:10.1016/s0002-8703(96)90386-5 · Cited by 82 · see citing works
Quantitative coronary arteriography: equipment and technical requirements
Reiber, J. H. C., van der Zwet, P. M. J., Land, C. D. V., et al. (1993) · Developments in cardiovascular medicine · doi:10.1007/978-94-011-1854-5_5 · Cited by 78 · see citing works
Studies on the mechanism of action of probucol
Steinberg, D. H. (1986) · The American Journal of Cardiology · doi:10.1016/0002-9149(86)90430-3 · Cited by 76 · see citing works
Simultaneous measurement of serum probucol and lipid-soluble antioxidants.
Elinder, L. S., & Walldius, G. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41890-5 · Cited by 54 · see citing works
O’Keefe, J. H., Stone, G. W., McCallister, B. D., et al. (1996) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)89325-3 · Cited by 53 · see citing works
Setsuda, M., Inden, M., Hiraoka, N., et al. (1993) · PubMed · Cited by 37 · see citing works
Lesp�rance, J., & Waters, D. D. (1992) · International journal of cardiac imaging · doi:10.1007/bf01146835 · Cited by 36 · see citing works
Self-citationYokoi, H., Yamaguchi, H., & Kuwabara, Y. (1996) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(96)82493-4 · Cited by 29 · see citing works
Relationship between Dose of Vitamin E Administered and Blood Levela
Brin, M. F., Fahn, S., LOFTUS, S., et al. (1989) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1989.tb14945.x · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Role of Endothelial Dysfunction in Atherosclerosis
Davignon, J., & Ganz, P. (2004) · Circulation · doi:10.1161/01.cir.0000131515.03336.f8 · Cited by 2,513 · see citing works
What is meant by intention to treat analysis? Survey of published randomised controlled trials
Hollis, S., & Campbell, F. (1999) · BMJ · doi:10.1136/bmj.319.7211.670 · Cited by 2,160 · see citing works
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007176.pub2 · Cited by 924 · see citing works
Sesso, H. D. (2008) · JAMA · doi:10.1001/jama.2008.600 · Cited by 913 · see citing works
Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture)
Félétou, M., & Vanhoutte, P. M. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00292.2006 · Cited by 818 · see citing works
Kinoshita, M., Yokote, K., Arai, H., Iida, M., Ishigaki, Y., Ishibashi, S., Umemoto, S., Egusa, G., Ohmura, H., Okamura, T., et al. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2017 · Cited by 813 · see citing works
Reactive oxygen species in cardiovascular disease
Sugamura, K., & Keaney (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.004 · Cited by 769 · see citing works
Natural and synthetic antioxidants: An updated overview
Augustyniak, A., Bartosz, G., Čipak, A., Duburs, G., Horáková, L., Łuczaj, W., Majekova, M., Odysseos, A. D., Rackova, L., Skrzydlewska, E., et al. (2010) · Free Radical Research · doi:10.3109/10715762.2010.508495 · Cited by 319 · see citing works
Tardif, J.-C., Ballantyne, C. M., Barter, P., Dasseux, J.-L., Fayad, Z. A., Guertin, M.-C., Kastelein, J. J. P., Keyserling, C., Klepp, H., Koenig, W., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu171 · Cited by 251 · see citing works
Self-citationSawayama, Y., Shimizu, C., Maeda, N., Tatsukawa, M., Kinukawa, N., Koyanagi, S., Kashiwagi, S., & Hayashi, J. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01783-1 · Cited by 226 · see citing works
Yamashita, S., Bujo, H., Arai, H., Harada-Shiba, M., Matsui, S., Fukushima, M., Saito, Y., Kita, T., & Matsuzawa, Y. (2008) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.e610 · Cited by 110 · see citing works
- Authors
- Tardif, J.-C., Côté, G., Lespérance, J., Bourassa, M., Lambert, J., Doucet, S., Bilodeau, L., Nattel, S., & de Guise, P.
- Affiliations
- Montreal Heart Institute (CA)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1997-08-07
- Volume
- 337
- Issue
- 6
- Pages
- 365-372
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2330609598
- Cited by
- 565
- References
- 42
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 9 · 2014: 12 · 2013: 6 · 2012: 12
- FWCI
- 62.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- probucol, multivitamins, antioxidant therapy, coronary restenosis, coronary angioplasty, neointima formation, vitamin E, beta-carotene, vitamin C, oxidative stress, vascular remodeling, repeat angioplasty, coronary heart disease prevention, lipid peroxidation inhibition
- MeSH terms
- Antioxidants, Ascorbic Acid, Coronary Disease, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Probucol, Recurrence, Vitamin E, Angioplasty, Balloon, Coronary, Treatment Outcome, Coronary Angiography, beta Carotene
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review