Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial

Department of Cardiology, Juntendo University, Tokyo, Japan.

OBJECTIVES: The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled study that investigated the effectiveness of probucol therapy in reducing the rate of restenosis after percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Antioxidants have an inhibitory effect on smooth muscle cell growth in experiments in vitro and in vivo, which suggests a possible pharmacologic effect on restenosis after PTCA. METHODS: One hundred one patients were randomly assigned to receive 1,000 mg/day of probucol or control (no lipid-lowering) therapy 4 weeks before PTCA. After 4 weeks of premedication, both groups underwent PTCA. Probucol was continued until follow-up angiography 24 weeks after PTCA. Angiographic results were analyzed at a core laboratory by quantitative coronary angiography. RESULTS: Dilation was successful in 46 of 50 patients in the probucol group and 45 of 51 in the control group. At follow-up angiography 24 weeks after angioplasty, angiographic restenosis occurred in 9 (23%) of 40 patients in the probucol group and 22 (58%) of 38 in the control group (p = 0.001). Minimal lumen diameter was 1.49 +/- 0.75 mm (mean +/- SD) in the probucol group and 1.13 +/- 0.65 mm in the control group (p = 0.02). Percent diameter stenosis at follow-up angiography in the probucol group was significantly lower than that in the control group (43.9% vs. 56.4%, p = 0.009). The late loss was 0.37 +/- 0.69 mm in the probucol group and 0.60 +/- 0.62 mm in the control group (p = 0.13). The loss/gain ratio was 0.32 +/- 0.74 in the probucol group and 0.56 +/- 0.81 in the control group (p = 0.059). Net gain was greater in the probucol group than in the control group (0.77 +/- 0.70 vs. 0.48 +/- 0.59 mm, p = 0.053). CONCLUSIONS: Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.

This article has been cited by other articles:

				A.-L. Levonen, E. Vahakangas, J. K. Koponen, and S. Yla-Herttuala Antioxidant Gene Therapy for Cardiovascular Disease: Current Status and Future Perspectives Circulation, April 22, 2008; 117(16): 2142 - 2150. [Abstract] [Full Text] [PDF]

				J. A. Reid, L. L. Lau, R. J. Hannon, B. Lee, I. S. Young, and C. V. Soong Decreased Antioxidant Vitamin Concentration May Be a Risk Factor for Recurrent Carotid Stenosis Vascular and Endovascular Surgery, September 1, 2007; 41(4): 330 - 334. [Abstract] [PDF]

				A. M Franks and S. F Gardner AGI-1067: A Novel Vascular Protectant for Prevention of Restenosis Ann. Pharmacother., January 1, 2006; 40(1): 66 - 73. [Abstract] [Full Text] [PDF]

				D. Zhuang, A.-C. Ceacareanu, B. Ceacareanu, and A. Hassid Essential role of protein kinase G and decreased cytoplasmic Ca2+ levels in NO-induced inhibition of rat aortic smooth muscle cell motility Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1859 - H1866. [Abstract] [Full Text] [PDF]

				R. S. Schwartz, N. A. Chronos, and R. Virmani Preclinical restenosis models and drug-eluting stents: Still important, still much to learn J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1373 - 1385. [Abstract] [Full Text] [PDF]

				K.-Y. Chyu, S. M. Babbidge, X. Zhao, R. Dandillaya, A. G. Rietveld, J. Yano, P. Dimayuga, B. Cercek, and P. K. Shah Differential Effects of Green Tea-Derived Catechin on Developing Versus Established Atherosclerosis in Apolipoprotein E-Null Mice Circulation, May 25, 2004; 109(20): 2448 - 2453. [Abstract] [Full Text] [PDF]

				A. K. Lau, S. B. Leichtweis, P. Hume, R. Mashima, J. Y. Hou, X. Chaufour, B. Wilkinson, N. H. Hunt, D. S. Celermajer, and R. Stocker Probucol Promotes Functional Reendothelialization in Balloon-Injured Rabbit Aortas Circulation, April 22, 2003; 107(15): 2031 - 2036. [Abstract] [Full Text] [PDF]

				J.-C. Tardif, J. Gregoire, L. Schwartz, L. Title, L. Laramee, F. Reeves, J. Lesperance, M. G. Bourassa, P. L. L'Allier, M. Glass, et al. Effects of AGI-1067 and Probucol After Percutaneous Coronary Interventions Circulation, February 4, 2003; 107(4): 552 - 558. [Abstract] [Full Text] [PDF]

				B. G. Brown, M. C. Cheung, A. C. Lee, X.-Q. Zhao, and A. Chait Antioxidant Vitamins and Lipid Therapy: End of a Long Romance? Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1535 - 1546. [Abstract] [Full Text] [PDF]

				G. Theilmeier, R. Quarck, P. Verhamme, M.-L. Bochaton-Piallat, M. Lox, H. Bernar, S. Janssens, M. Kockx, G. Gabbiani, D. Collen, et al. Hypercholesterolemia impairs vascular remodelling after porcine coronary angioplasty Cardiovasc Res, August 1, 2002; 55(2): 385 - 395. [Abstract] [Full Text] [PDF]

				R. J. Pettersen, Z. A. Muna, K. K.J. Kuiper, E. Svendsen, F. Muller, P. Aukrust, R. K. Berge, and J. Erik Nordrehaug Sustained retention of tetradecylthioacetic acid after local delivery reduces angioplasty-induced coronary stenosis in the minipig Cardiovasc Res, November 1, 2001; 52(2): 306 - 313. [Abstract] [Full Text] [PDF]

				M. Aoki, T. Nata, R. Morishita, H. Matsushita, H. Nakagami, K. Yamamoto, K. Yamazaki, M. Nakabayashi, T. Ogihara, and Y. Kaneda Endothelial Apoptosis Induced by Oxidative Stress Through Activation of NF-{kappa}B: Antiapoptotic Effect of Antioxidant Agents on Endothelial Cells Hypertension, July 1, 2001; 38(1): 48 - 55. [Abstract] [Full Text] [PDF]

				Y. Shi, R. Niculescu, D. Wang, S. Patel, K. L. Davenpeck, and A. Zalewski Increased NAD(P)H Oxidase and Reactive Oxygen Species in Coronary Arteries After Balloon Injury Arterioscler. Thromb. Vasc. Biol., May 1, 2001; 21(5): 739 - 745. [Abstract] [Full Text] [PDF]

				L. C.P. Azevedo, M. d. A. Pedro, L. C. Souza, H. P. de Souza, M. Janiszewski, P. L. da Luz, and F. R.M. Laurindo Oxidative stress as a signaling mechanism of the vascular response to injury: The redox hypothesis of restenosis Cardiovasc Res, August 18, 2000; 47(3): 436 - 445. [Abstract] [Full Text] [PDF]

				D. S Ettenson and E. R Edelman Local drug delivery: an emerging approach in the treatment of restenosis Vascular Medicine, May 1, 2000; 5(2): 97 - 102. [Abstract] [PDF]

				A. Betriu, M. Masotti, A. Serra, J. Alonso, F. Fernandez-Aviles, F. Gimeno, T. Colman, J. Zueco, J. L. Delcan, E. Garcia, et al. Randomized comparison of coronary stent implantation and balloon angioplasty in the treatment of de novo coronary artery lesions (START): A four-year follow-up J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1498 - 1506. [Abstract] [Full Text] [PDF]

				A. Mezzetti, M. D. Guglielmi, S. D. Pierdomenico, F. Costantini, F. Cipollone, D. De Cesare, T. Bucciarelli, S. Ucchino, F. Chiarelli, F. Cuccurullo, et al. Increased Systemic Oxidative Stress After Elective Endarterectomy : Relation to Vascular Healing and Remodeling Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2659 - 2665. [Abstract] [Full Text] [PDF]

				K. J. Harjai Potential New Cardiovascular Risk Factors: Left Ventricular Hypertrophy, Homocysteine, Lipoprotein(a), Triglycerides, Oxidative Stress, and Fibrinogen Ann Intern Med, September 7, 1999; 131(5): 376 - 386. [Abstract] [Full Text] [PDF]

				D. L. Tribble Antioxidant Consumption and Risk of Coronary Heart Disease: Emphasis on Vitamin C, Vitamin E, and ß-Carotene : A Statement for Healthcare Professionals From the American Heart Association Circulation, February 2, 1999; 99(4): 591 - 595. [Full Text] [PDF]

				M. J. Pollman, J. L. Hall, and G. H. Gibbons Determinants of Vascular Smooth Muscle Cell Apoptosis After Balloon Angioplasty Injury : Influence of Redox State and Cell Phenotype Circ. Res., January 22, 1999; 84(1): 113 - 121. [Abstract] [Full Text] [PDF]

				G. Cote, J.-C. Tardif, J. Lesperance, J. Lambert, M. Bourassa, R. Bonan, G. Gosselin, M. Joyal, J.-F. Tanguay, S. Nattel, et al. Effects of Probucol on Vascular Remodeling After Coronary Angioplasty Circulation, January 12, 1999; 99(1): 30 - 35. [Abstract] [Full Text] [PDF]

				B. D. Klugherz, N. Meneveau, W. Chen, F. Wade-Whittaker, G. Papandreou, R. Levy, and R. L. Wilensky Sustained Intramural Retention and Regional Redistribution Following Local Vascular Delivery of Polylactic-Coglycolic Acid and Liposomal Nanoparticulate Formulations Containing Probucol Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(3): 167 - 174. [Abstract] [PDF]

				J. Binko, S. Meachem, and H. Majewski Endothelium removal induces iNOS in rat aorta in organ culture, leading to tissue damage Am J Physiol Endocrinol Metab, January 1, 1999; 276(1): E125 - E134. [Abstract] [Full Text] [PDF]

				E. R. Edelman Vessel Size, Antioxidants, and Restenosis : Never Too Small, Not Too Little, but Often Too Late Circulation, February 10, 1998; 97(5): 416 - 420. [Full Text] [PDF]