Author + information
- Received December 4, 2009
- Revision received January 29, 2010
- Accepted February 2, 2010
- Published online May 25, 2010.
- Stephen J. Nicholls, MBBS, PhD⁎,†,‡,⁎ (, )
- Amy Hsu, MS⁎,
- Kathy Wolski, MPH⁎,
- Bo Hu, PhD§,
- Ozgur Bayturan, MD⁎,
- Andrea Lavoie, MD⁎,
- Kiyoko Uno, MD, PhD⁎,
- E. Murat Tuzcu, MD⁎ and
- Steven E. Nissen, MD⁎
- ↵⁎Reprint requests and correspondence:
Dr. Stephen J. Nicholls, Department of Cardiovascular Medicine, Heart & Vascular Institute, Mail Code JJ-65, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195
Objectives The aim of this study was to investigate the relationship between intravascular ultrasound (IVUS)-derived measures of atherosclerosis and cardiovascular outcomes.
Background IVUS has been used in clinical trials to evaluate the effect of medical therapies on coronary atheroma progression.
Methods Coronary plaque progression was evaluated in 4,137 patients in 6 clinical trials that used serial IVUS. The relationship between baseline and change in percent atheroma volume (PAV) and total atheroma volume with incident major adverse cardiovascular events (MACE) was investigated.
Results PAV increased by 0.3% (p < 0.001), and 19.9% of subjects experienced MACE (0.9% death, 1.8% myocardial infarction, 18.9% coronary revascularization). Greater baseline PAVs were observed in patients who experienced myocardial infarctions (42.2 ± 9.6% vs. 38.6 ± 9.1%, p = 0.001), coronary revascularization (41.2 ± 9.3% vs. 38.1 ± 9.0%, p < 0.001), or MACE (41.3 ± 9.2% vs. 38.0 ± 9.0%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.32-fold (95% confidence interval: 1.22 to 1.42; p < 0.001) greater likelihood of experiencing a MACE. During follow-up (21.1 ± 3.7 months), greater increases in PAV, but not total atheroma volume, were observed in subjects who experienced MACE compared with those who did not (0.95 ± 0.19% vs. 0.46 ± 0.16%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.20-fold (95% confidence interval: 1.10 to 1.31; p < 0.001) greater risk for MACE. Multivariate analysis revealed that factors associated with MACE included baseline PAV (p < 0.0001), change in PAV (p = 0.002), smoking (p = 0.0002) and hypertension (p = 0.01).
Conclusions A direct relationship was observed between the burden of coronary atherosclerosis, its progression, and adverse cardiovascular events. The relationship between disease progression and outcomes largely reflected the need for coronary revascularization. These data support the use of atherosclerosis imaging with IVUS in the evaluation of novel antiatherosclerotic therapies.
The REVERSAL, CAMELOT, and ILLUSTRATE studies were sponsored by Pfizer. The ACTIVATE study was sponsored by Daiichi Sankyo. The PERISCOPE study was sponsored by Takeda. The STRADIVARIUS study was sponsored by Sanofi-Aventis. Dr. Nicholls has received honoraria from Pfizer, AstraZeneca, Takeda, and Merck/Schering-Plough; consultancy fees from AstraZeneca, Pfizer, Roche, Novo Nordisk, Merck/Schering-Plough, LipoScience, and Anthera Pharmaceuticals; and research support from AstraZeneca, Lipid Sciences, Novartis, Eli Lilly, Anthera, and Resverlogix. Dr. Lavoie has received honoraria from Pfizer, AstraZeneca, Bayer, Servier, and Bristol-Myers Squibb. Dr. Tuzcu has received consultancy fees from Pfizer and honoraria from Pfizer and Merck. Dr. Nissen has received research support from AstraZeneca, Eli Lilly, Pfizer, Takeda, Daiichi Sankyo, Novartis, Roche, Resverlogix, and Sanofi-Aventisand has consulted for a number of pharmaceutical companies without financial compensation; all of Dr. Nissen's honoraria, consulting fees, or any other payments from any for-profit entity are paid directly to charity, so that neither income nor any tax deduction is received.
- Received December 4, 2009.
- Revision received January 29, 2010.
- Accepted February 2, 2010.
- American College of Cardiology Foundation