Circulation. 2004;110:3512-3517
Published online before print November 10, 2004, doi: 10.1161/01.CIR.0000148955.19792.8D
Published online before print November 10, 2004, doi: 10.1161/01.CIR.0000148955.19792.8D
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;110:3512-3517.)
© 2004 American Heart Association, Inc.
Late-Breaking Clinical Trials |
Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2
A Double-Blind, Placebo-Controlled Study of Extended-Release Niacin on Atherosclerosis Progression in Secondary Prevention Patients Treated With Statins
From the Cardiology Service, Walter Reed Army Medical Center, Washington, DC.
Correspondence to Allen J. Taylor, MD, LTC, MC, USA, Director, Cardiovascular Research, Cardiology Service, Walter Reed Army Medical Center, 6900 Georgia Ave, NW, Bldg 2, Room 3L28, Washington, DC 20307-5001. E-mail allen.taylor{at}na.amedd.army.mil
Received October 1, 2004; accepted October 6, 2004.
Abstract
Background— Niacin reduces coronary heart disease morbidity and mortality when taken either alone or in combination with statins; however, the incremental impact of adding niacin to background statin therapy is unknown.
Methods and Results— This was a double-blind randomized placebo-controlled study of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease and low levels of high-density lipoprotein cholesterol (HDL-C; <45 mg/dL). The primary end point was the change in common carotid intima-media thickness (CIMT) after 1 year. Baseline CIMT (0.884±0.234 mm), low-density lipoprotein cholesterol (89±20 mg/dL), and HDL-C (40±7 mg/dL) were comparable in the placebo and niacin groups. Adherence to niacin exceeded 90%, and 149 patients (89.2%) completed the study. HDL-C increased 21% (39 to 47 mg/dL) in the niacin group. After 12 months, mean CIMT increased significantly in the placebo group (0.044±0.100 mm; P<0.001) and was unchanged in the niacin group (0.014±0.104 mm; P=0.23). Although the overall difference in IMT progression between the niacin and placebo groups was not statistically significant (P=0.08), niacin significantly reduced the rate of IMT progression in subjects without insulin resistance (P=0.026). Clinical cardiovascular events occurred in 3 patients treated with niacin (3.8%) and 7 patients treated with placebo (9.6%; P=0.20).
Conclusions— The addition of extended-release niacin to statin therapy slowed the progression of atherosclerosis among individuals with known coronary heart disease and moderately low HDL-C.
Key Words: atherosclerosis • risk factors • lipids
Related Article:
Circulation 2004 110: 3509-3511.
This article has been cited by other articles:
 |
|
 |
|
  D J Hausenloy and D M Yellon Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels Heart, June 1, 2008; 94(6): 706 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Movva and D. J. Rader Laboratory Assessment of HDL Heterogeneity and Function Clin. Chem., May 1, 2008; 54(5): 788 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Guyton, B. G. Brown, S. Fazio, A. Polis, J. E. Tomassini, and A. M. Tershakovec Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia. J. Am. Coll. Cardiol., April 22, 2008; 51(16): 1564 - 1572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Davidson, P. M. Meyer, S. Haffner, S. Feinstein, R. D'Agostino Sr, G. T. Kondos, A. Perez, Z. Chen, and T. Mazzone Increased High-Density Lipoprotein Cholesterol Predicts the Pioglitazone-Mediated Reduction of Carotid Intima-Media Thickness Progression in Patients With Type 2 Diabetes Mellitus Circulation, April 22, 2008; 117(16): 2123 - 2130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Brunzell, M. Davidson, C. D. Furberg, R. B. Goldberg, B. V. Howard, J. H. Stein, and J. L. Witztum Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus Conference Report From the American Diabetes Association and the American College of Cardiology Foundation J. Am. Coll. Cardiol., April 15, 2008; 51(15): 1512 - 1524. [Full Text] [PDF]
|
|
|
|
 |
|
 B. V. Howard, M. J. Roman, R. B. Devereux, J. L. Fleg, J. M. Galloway, J. A. Henderson, Wm. J. Howard, E. T. Lee, M. Mete, B. Poolaw, et al. Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes: The SANDS Randomized Trial JAMA, April 9, 2008; 299(14): 1678 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Brown and A. J. Taylor Does ENHANCE Diminish Confidence in Lowering LDL or in Ezetimibe? N. Engl. J. Med., April 3, 2008; 358(14): 1504 - 1507. [Full Text] [PDF]
|
|
|
|
|
|
J. J.P. Kastelein, F. Akdim, E. S.G. Stroes, A. H. Zwinderman, M. L. Bots, A. F.H. Stalenhoef, F. L.J. Visseren, E. J.G. Sijbrands, M. D. Trip, E. A. Stein, et al. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia N. Engl. J. Med., April 3, 2008; 358(14): 1431 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J.P. Kastelein and E. de Groot Ultrasound imaging techniques for the evaluation of cardiovascular therapies Eur. Heart J., April 1, 2008; 29(7): 849 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Brunzell, M. Davidson, C. D. Furberg, R. B. Goldberg, B. V. Howard, J. H. Stein, and J. L. Witztum Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation Diabetes Care, April 1, 2008; 31(4): 811 - 822. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ferns and V. Keti HDL-cholesterol modulation and its impact on the management of cardiovascular risk Ann Clin Biochem, March 1, 2008; 45(2): 122 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. deGoma, N. J. Leeper, and P. A. Heidenreich Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol. J. Am. Coll. Cardiol., January 1, 2008; 51(1): 49 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Lavie and R. V. Milani Shedding light on high-density lipoprotein cholesterol: the post-ILLUMINATE era. J. Am. Coll. Cardiol., January 1, 2008; 51(1): 56 - 58. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Muller, H. Mehling, B. Otto, R. Bergmann-Lips, F. Luft, J. Jordan, and R. Kettritz Niacin Lowers Serum Phosphate and Increases HDL Cholesterol in Dialysis Patients Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1249 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Criqui Triglycerides and Coronary Heart Disease Revisited (Again) Ann Intern Med, September 18, 2007; 147(6): 425 - 427. [Full Text] [PDF]
|
|
|
|
|
|
J. D. Brunzell Hypertriglyceridemia N. Engl. J. Med., September 6, 2007; 357(10): 1009 - 1017. [Full Text] [PDF]
|
|
|
|
|
|
I. M. Singh, M. H. Shishehbor, and B. J. Ansell High-Density Lipoprotein as a Therapeutic Target: A Systematic Review JAMA, August 15, 2007; 298(7): 786 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yanai, H. Yoshida, Y. Tomono, and N. Tada Atherosclerosis imaging in statin intervention trials QJM, May 1, 2007; 100(5): 253 - 262. [Full Text] [PDF]
|
|
|
|
|
|
J. M S Lee and R. P Choudhury Prospects for atherosclerosis regression through increase in high-density lipoprotein and other emerging therapeutic targets Heart, May 1, 2007; 93(5): 559 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J.P. Kastelein, S. I. van Leuven, L. Burgess, G. W. Evans, J. A. Kuivenhoven, P. J. Barter, J. H. Revkin, D. E. Grobbee, W. A. Riley, C. L. Shear, et al. Effect of Torcetrapib on Carotid Atherosclerosis in Familial Hypercholesterolemia N. Engl. J. Med., April 19, 2007; 356(16): 1620 - 1630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Brown A Direct Comparison of Intravascular Ultrasound and Quantitative Coronary Arteriography: Implications for Measures of Atherosclerosis as Clinical Surrogates Circulation, April 10, 2007; 115(14): 1824 - 1826. [Full Text] [PDF]
|
|
|
|
|
|
S. E. Nissen, J.-C. Tardif, S. J. Nicholls, J. H. Revkin, C. L. Shear, W. T. Duggan, W. Ruzyllo, W. B. Bachinsky, G. P. Lasala, E. M. Tuzcu, et al. Effect of Torcetrapib on the Progression of Coronary Atherosclerosis N. Engl. J. Med., March 29, 2007; 356(13): 1304 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sanossian, J. L. Saver, M. Navab, and B. Ovbiagele High-Density Lipoprotein Cholesterol: An Emerging Target for Stroke Treatment Stroke, March 1, 2007; 38(3): 1104 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Nicholls, E. M. Tuzcu, I. Sipahi, A. W. Grasso, P. Schoenhagen, T. Hu, K. Wolski, T. Crowe, M. Y. Desai, S. L. Hazen, et al. Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis JAMA, February 7, 2007; 297(5): 499 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Benyo, A. Gille, C. L. Bennett, B. E. Clausen, and S. Offermanns Nicotinic Acid-Induced Flushing Is Mediated by Activation of Epidermal Langerhans Cells Mol. Pharmacol., December 1, 2006; 70(6): 1844 - 1849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. McKenney, M. H. Davidson, C. L. Shear, and J. H. Revkin Efficacy and Safety of Torcetrapib, a Novel Cholesteryl Ester Transfer Protein Inhibitor, in Individuals With Below-Average High-Density Lipoprotein Cholesterol Levels on a Background of Atorvastatin J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1782 - 1790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Sirtori HDL and the progression of atherosclerosis: new insights Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F4 - F9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bruckert Epidemiology of low HDL-cholesterol: results of studies and surveys Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F17 - F22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Drexel Reducing risk by raising HDL-cholesterol: the evidence Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F23 - F29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Wierzbicki Diabetic dyslipidaemia: the triad Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F30 - F33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tschoepe and B. Stratmann Plaque stability and plaque regression: new insights Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F34 - F39. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Assmann Dyslipidaemia and global cardiovascular risk: clinical issues Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F40 - F46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Barter Options for therapeutic intervention: how effective are the different agents? Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F47 - F53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Brown Niaspan(R) in the management of dyslipidaemia: the evidence Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F60 - F67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Reasner Achieving the therapeutic benefits of Niaspan(R) in daily practice Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F68 - F73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Taylor Evidence to support aggressive management of HDL-cholesterol: implications of recent trials Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F74 - F80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Crouse III Thematic review series: Patient-Oriented Research. Imaging atherosclerosis: state of the art J. Lipid Res., August 1, 2006; 47(8): 1677 - 1699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Circulation, June 20, 2006; 113(24): e873 - e923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Stroke, June 1, 2006; 37(6): 1583 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Junyent, M. Cofan, I. Nunez, R. Gilabert, D. Zambon, and E. Ros Influence of HDL Cholesterol on Preclinical Carotid Atherosclerosis in Familial Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1107 - 1113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Cheng, T.-J. Wu, K. K. Wu, C. Sturino, K. Metters, K. Gottesdiener, S. D. Wright, Z. Wang, G. O'Neill, E. Lai, et al. Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans PNAS, April 25, 2006; 103(17): 6682 - 6687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Duffy and D. J. Rader Emerging Therapies Targeting High-Density Lipoprotein Metabolism and Reverse Cholesterol Transport Circulation, February 28, 2006; 113(8): 1140 - 1150. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Raggi, A. Taylor, Z. Fayad, D. O'Leary, S. Nissen, D. Rader, and L. J. Shaw Atherosclerotic Plaque Imaging: Contemporary Role in Preventive Cardiology Arch Intern Med, November 14, 2005; 165(20): 2345 - 2353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Raggi, A. Bellasi, and C. Ratti Ischemia Imaging and Plaque Imaging in Diabetes: Complementary tools to improve cardiovascular risk management Diabetes Care, November 1, 2005; 28(11): 2787 - 2794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
2nd International Symposium on Triglycerides and HDL: Lipid abnormalities and their treatment Diabetes Care, November 1, 2005; 28(11): 2795 - 2802. [Full Text] [PDF]
|
|
|
|
|
|
M. D. Ashen and R. S. Blumenthal Low HDL Cholesterol Levels N. Engl. J. Med., September 22, 2005; 353(12): 1252 - 1260. [Full Text] [PDF]
|
|
|
|
|
|
J. J.P. Kastelein The realities of dyslipidaemia: what do the studies tell us? Eur. Heart J. Suppl., July 1, 2005; 7(suppl_F): F27 - F33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Brown Maximizing coronary disease risk reduction using nicotinic acid combined with LDL-lowering therapy Eur. Heart J. Suppl., July 1, 2005; 7(suppl_F): F34 - F40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Nicholls and S. E. Nissen Strategies to promote HDL-C: an emerging therapeutic target Eur. Heart J., May 1, 2005; 26(9): 853 - 855. [Full Text] [PDF]
|
|
|
|
|
|
E. D. Beishuizen, M. A. van de Ree, J. W. Jukema, J. T. Tamsma, and M. V. Huisman Two-Year Statin Therapy Does Not Alter the Progression of Intima-Media Thickness in Patients With Type 2 Diabetes Without Manifest Cardio-vascular Disease: Response to Cicero et al. Diabetes Care, May 1, 2005; 28(5): 1263 - 1264. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Lee and R. P Choudhury ARBITER 2: targeting HDL to retard atherosclerosis progression: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2 The British Journal of Diabetes & Vascular Disease, March 1, 2005; 5(2): 78 - 80. [PDF]
|
|
|
|
|
|
S. M. Grundy Atherosclerosis Imaging and the Future of Lipid Management Circulation, December 7, 2004; 110(23): 3509 - 3511. [Full Text] [PDF]
|
|