on January 6, 2003
Published online before print January 6, 2003, doi: 10.1161/01.CIR.0000047525.58618.3C
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 13, 2002
From the Montreal Heart Institute (J.C.T., J.G., J. Lespérance, M.G.B., P.L.L., J. Lambert, M.-C.G.), Montreal, Canada; Toronto General Hospital (L.S.), Toronto, Canada; Queen Elizabeth II Hospital (L.T.), Halifax, Canada; Ottawa Heart Institute (L.L.), Ottawa, Canada; Notre-Dame Hospital (F.R.), Montreal, Canada; and AtheroGenics (M.G.), Alpharetta, Ga. * To whom correspondence should be addressed. E-mail: tardifjc{at}icm.umontreal.ca.
Background—AGI-1067, a metabolically stable modification of probucol, is an equipotent antioxidant to probucol but is pharmacologically distinct. In a multicenter trial, we studied whether AGI-1067 reduces restenosis assessed by intravascular ultrasound (IVUS) after percutaneous coronary intervention (PCI) compared with placebo and probucol used as a positive control. Methods and Results—Two weeks before PCI, 305 patients were randomly assigned to 1 of 5 treatment groups: placebo, probucol 500 mg BID, or AGI-1067 70, 140, or 280 mg once daily. Patients were treated for 2 weeks before and 4 weeks after PCI. Baseline and 6-month follow-up IVUS were interpreted by a blinded core laboratory. Stents were used in 85% of patients. Luminal area at the PCI site at follow-up was 2.66±1.58 mm2 for placebo, 3.69±2.69 mm2 for probucol, 2.75±1.76 mm2 for AGI-1067 70 mg, 3.17±2.26 mm2 for AGI-1067 140 mg, and 3.36±2.12 mm2 for AGI-1067 280 mg (P=0.02 for the dose-response relationship; P Conclusions—AGI-1067 and probucol reduce restenosis after PCI. In contrast to probucol, AGI-1067 did not cause prolongation of the QTc interval and improved lumen dimensions of reference segments, suggestive of a direct effect on atherosclerosis.
Revised on October 18, 2002
Accepted on October 20, 2002
Effects of AGI-1067 and Probucol After Percutaneous Coronary Interventions
Jean-Claude Tardif MD*,
0.05 for AGI-1067 280 mg and probucol versus placebo). There was a mean narrowing of 5.3 mm3 of reference segment lumen in the placebo group and an enlargement in the AGI-1067 140- and 280-mg groups at follow-up (P=0.05 for 140 mg). An increase in QTc interval >60 ms occurred in 4.8% of placebo patients, 17.4% of probucol patients, and 4.8%, 2.4%, and 2.5% of patients in the AGI-1067 groups (P=0.02).
Key words: antioxidants • coronary disease • atherosclerosis • restenosis
This article has been cited by other articles:
 |
|
 |
|
  B. J. Wu, R. G. Midwinter, C. Cassano, K. Beck, Y. Wang, D. Changsiri, J. R. Gamble, and R. Stocker Heme Oxygenase-1 Increases Endothelial Progenitor Cells Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1537 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Byrne, J. Mehilli, R. Iijima, S. Schulz, J. Pache, M. Seyfarth, A. Schomig, A. Kastrati, and for the Intracoronary Stenting and Angiographic Re A polymer-free dual drug-eluting stent in patients with coronary artery disease: a randomized trial vs. polymer-based drug-eluting stents Eur. Heart J., April 2, 2009; 30(8): 923 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Chevillet, G. J. Park, A. Bedalov, J. A. Simon, and V. I. Vasioukhin Identification and characterization of small-molecule inhibitors of hepsin Mol. Cancer Ther., October 1, 2008; 7(10): 3343 - 3351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Boekholdt, R. J. de Winter, and J. J.P. Kastelein Inhibition of Lipoprotein-Associated Phospholipase Activity by Darapladib: Shifting Gears in Cardiovascular Drug Development: Are Antiinflammatory Drugs the Next Frontier? Circulation, September 9, 2008; 118(11): 1120 - 1122. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Luyendyk, J. D. Piper, M. Tencati, K. V. Reddy, T. Holscher, R. Zhang, J. Luchoomun, X. Chen, W. Min, C. Kunsch, et al. A Novel Class of Antioxidants Inhibit LPS Induction of Tissue Factor by Selective Inhibition of the Activation of ASK1 and MAP Kinases Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1857 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S Wierzbicki Voodoo medicine -- cardiovascular trials jinxed in New Orleans: Dr Anthony Wierzbicki discusses highlights of the 56th Annual Scientific Session of American College of Cardiology held at Morial Conventions Centre in New Orleans March 24th--27th, 2007 The British Journal of Diabetes & Vascular Disease, May 1, 2007; 7(3): 142 - 144. [PDF]
|
|
|
|
 |
|
 B. J. Wu, N. Di Girolamo, K. Beck, C. G. Hanratty, K. Choy, J. Y. Hou, M. R. Ward, and R. Stocker Probucol [4,4'-[(1-Methylethylidene)bis(thio)]bis-[2,6-bis(1,1-dimethylethyl)phenol]] Inhibits Compensatory Remodeling and Promotes Lumen Loss Associated with Atherosclerosis in Apolipoprotein E-Deficient Mice J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 477 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Tardif, J. Gregoire, P. L. L'Allier, R. Ibrahim, J. Lesperance, T. M. Heinonen, S. Kouz, C. Berry, R. Basser, M.-A. Lavoie, et al. Effects of Reconstituted High-Density Lipoprotein Infusions on Coronary Atherosclerosis: A Randomized Controlled Trial JAMA, April 18, 2007; 297(15): 1675 - 1682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-L. Levonen, M. Inkala, T. Heikura, S. Jauhiainen, H.-K. Jyrkkanen, E. Kansanen, K. Maatta, E. Romppanen, P. Turunen, J. Rutanen, et al. Nrf2 Gene Transfer Induces Antioxidant Enzymes and Suppresses Smooth Muscle Cell Growth In Vitro and Reduces Oxidative Stress in Rabbit Aorta In Vivo Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 741 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Waxman, F. Ishibashi, and J. E. Muller Detection and Treatment of Vulnerable Plaques and Vulnerable Patients: Novel Approaches to Prevention of Coronary Events Circulation, November 28, 2006; 114(22): 2390 - 2411. [Full Text] [PDF]
|
|
|
|
|
|
R. Stocker and M. A. Perrella Heme Oxygenase-1: A Novel Drug Target for Atherosclerotic Diseases? Circulation, November 14, 2006; 114(20): 2178 - 2189. [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Tardif, T. Heinonen, D. Orloff, and P. Libby Vascular Biomarkers and Surrogates in Cardiovascular Disease Circulation, June 27, 2006; 113(25): 2936 - 2942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Heinecke Lipoprotein oxidation in cardiovascular disease: chief culprit or innocent bystander? J. Exp. Med., April 17, 2006; 203(4): 813 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Wu, K. Kathir, P. K. Witting, K. Beck, K. Choy, C. Li, K. D. Croft, T. A. Mori, D. Tanous, M. R. Adams, et al. Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging J. Exp. Med., April 17, 2006; 203(4): 1117 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Nissen, S. J. Nicholls, I. Sipahi, P. Libby, J. S. Raichlen, C. M. Ballantyne, J. Davignon, R. Erbel, J. C. Fruchart, J.-C. Tardif, et al. Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis: The ASTEROID Trial JAMA, April 5, 2006; 295(13): 1556 - 1565. [Abstract] [Full Text] [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]
|
|
|
|
|
|
K. Choy, K. Beck, F. Y. Png, B. J. Wu, S. B. Leichtweis, S. R. Thomas, J. Y. Hou, K. D. Croft, T. A. Mori, and R. Stocker Processes Involved in the Site-Specific Effect of Probucol on Atherosclerosis in Apolipoprotein E Gene Knockout Mice Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1684 - 1690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Guedes, P.-F. Keller, P. L. L'Allier, J. Lesperance, J. Gregoire, and J.-C. Tardif Long-term safety of intravascular ultrasound in nontransplant, nonintervened, atherosclerotic coronary arteries J. Am. Coll. Cardiol., February 15, 2005; 45(4): 559 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yonekawa and J. M. Harlan Targeting leukocyte integrins in human diseases J. Leukoc. Biol., February 1, 2005; 77(2): 129 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Tardif, J. Gregoire, P. L. L'Allier, T. J. Anderson, O. Bertrand, F. Reeves, L. M. Title, F. Alfonso, E. Schampaert, A. Hassan, et al. Effects of the Acyl Coenzyme A:Cholesterol Acyltransferase Inhibitor Avasimibe on Human Atherosclerotic Lesions Circulation, November 23, 2004; 110(21): 3372 - 3377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Deng, B. J. Wu, P. K. Witting, and R. Stocker Probucol Protects Against Smooth Muscle Cell Proliferation by Upregulating Heme Oxygenase-1 Circulation, September 28, 2004; 110(13): 1855 - 1860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R.P Agema, P. S Monraats, A. H Zwinderman, R. J de Winter, R. A Tio, P. A.F.M Doevendans, J. Waltenberger, M. P.M de Maat, R. R Frants, D. E Atsma, et al. Current PTCA practice and clinical outcomes in The Netherlands: the real world in the pre-drug-eluting stent era Eur. Heart J., July 1, 2004; 25(13): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kunsch, J. Luchoomun, J. Y. Grey, L. K. Olliff, L. B. Saint, R. F. Arrendale, M. A. Wasserman, U. Saxena, and R. M. Medford Selective Inhibition of Endothelial and Monocyte Redox-Sensitive Genes by AGI-1067: A Novel Antioxidant and Anti-Inflammatory Agent J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 820 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Winter, A. M. Morawski, S. D. Caruthers, R. W. Fuhrhop, H. Zhang, T. A. Williams, J. S. Allen, E. K. Lacy, J. D. Robertson, G. M. Lanza, et al. Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With {alpha}v{beta}3-Integrin-Targeted Nanoparticles Circulation, November 4, 2003; 108(18): 2270 - 2274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Tardif, J. Gregoire, P.L. Lallier, and M. Joyal Chronic heart rate reduction with ivabradine and prevention of atherosclerosis progression assessed using intravascular ultrasound Eur. Heart J. Suppl., September 1, 2003; 5(suppl_G): G46 - G51. [Abstract] [PDF]
|
|
|
|
 |
|
 D. G Harrison, Hua Cai, U. Landmesser, and K. K Griendling The Pickering Lecture British Hypertension Society, 10th September 2002: Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, June 1, 2003; 4(2): 51 - 61. [Abstract] [PDF]
|
|
|
|
|
|
C. L. Sundell, P. K. Somers, C. Q. Meng, L. K. Hoong, K.-L. Suen, R. R. Hill, L. K. Landers, A. Chapman, D. Butteiger, M. Jones, et al. AGI-1067: A Multifunctional Phenolic Antioxidant, Lipid Modulator, Anti-Inflammatory and Antiatherosclerotic Agent J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1116 - 1123. [Abstract] [Full Text] [PDF]
|
|