Author + information
- Received August 28, 2008
- Revision received October 8, 2008
- Accepted October 14, 2008
- Published online December 16, 2008.
- Jerome L. Fleg, MD⁎,
- Mihriye Mete, PhD†,
- Barbara V. Howard, PhD†,
- Jason G. Umans, MD, PhD†,
- Mary J. Roman, MD‡,
- Robert E. Ratner, MD†,
- Angela Silverman, MSN, CANP†,
- James M. Galloway, MD§,
- Jeffrey A. Henderson, MD, MPH∥,
- Matthew R. Weir, MD¶,
- Charlton Wilson, MD#,
- Mario Stylianou, PhD⁎ and
- Wm. James Howard, MD⁎⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Wm. James Howard, MedStar Research Institute, 6495 New Hampshire Avenue, Hyattsville, Maryland 20783
Objectives This secondary analysis from the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial examines the effects of lowering low-density lipoprotein cholesterol (LDL-C) with statins alone versus statins plus ezetimibe on common carotid artery intima-media thickness (CIMT) in patients with type 2 diabetes and no prior cardiovascular event.
Background It is unknown whether the addition of ezetimibe to statin therapy affects subclinical atherosclerosis.
Methods Within an aggressive group (target LDL-C ≤70 mg/dl; non–high-density lipoprotein cholesterol ≤100 mg/dl; systolic blood pressure ≤115 mm Hg), change in CIMT over 36 months was compared in diabetic individuals >40 years of age receiving statins plus ezetimibe versus statins alone. The CIMT changes in both aggressive subgroups were compared with changes in the standard subgroups (target LDL-C ≤100 mg/dl; non–high-density lipoprotein cholesterol ≤130 mg/dl; systolic blood pressure ≤130 mm Hg).
Results Mean (95% confidence intervals) LDL-C was reduced by 31 (23 to 37) mg/dl and 32 (27 to 38) mg/dl in the aggressive group receiving statins plus ezetimibe and statins alone, respectively, compared with changes of 1 (−3 to 6) mg/dl in the standard group (p < 0.0001) versus both aggressive subgroups. Within the aggressive group, mean CIMT at 36 months regressed from baseline similarly in the ezetimibe (−0.025 [−0.05 to 0.003] mm) and nonezetimibe subgroups (−0.012 [−0.03 to 0.008] mm) but progressed in the standard treatment arm (0.039 [0.02 to 0.06] mm), intergroup p < 0.0001.
Conclusions Reducing LDL-C to aggressive targets resulted in similar regression of CIMT in patients who attained equivalent LDL-C reductions from a statin alone or statin plus ezetimibe. Common carotid artery IMT increased in those achieving standard targets. (Stop Atherosclerosis in Native Diabetics Study [SANDS]; NCT00047424)
Funding was provided by the National Heart, Lung, and Blood Institute, National Institutes of Health, NHLBI grant (1U01 HL67031-01A1). Medications were donated by First Horizon Pharmacy (Triglide), Merck and Co. (Cozaar/Hyzaar), and Pfizer, Inc. (Lipitor). Dr. B. V. Howard has served on the Advisory Boards of Merck, Schering-Plough, the Egg Nutrition Council, and General Mills and has received research support from Merck and Pfizer. Dr. Wm. J. Howard has received research support from Pfizer, AstraZeneca, Merck, and Schering-Plough; has served as a consultant for Merck, Schering-Plough, Pfizer, and Reliant; and has served on the Speakers' Bureaus for Merck, Schering-Plough, Pfizer, AstraZeneca, Abbott, and Daichi Sankyo. Dr. Ratner has received research support from AstraZeneca, Bayhill Therapeutics, Boehringer Ingelheim, GlaxoSmithKline, Merck, NovoNordisk, Pfizer, Takeda, and Veraligh; has served on the Advisory Boards of Amylin, AstraZeneca, Eli Lilly, GlaxoSmithKline, Lifescan, NovoNordisk, Sanofi-Aventis, Takeda, and Tethys Bioscience; and owns stock in Merck, Johnson & Johnson, and Abbott. Dr. Weir has served on the Speakers' Bureaus of Merck Sharp & Dohme, Novartis, Boehringer Ingelheim, and Bristol-Myers Squibb. The opinions expressed in this report are those of the authors and do not necessarily reflect the views of the Indian Health Service, the Office of Public Health and Science, or the National Institutes of Health.
- Received August 28, 2008.
- Revision received October 8, 2008.
- Accepted October 14, 2008.
- American College of Cardiology Foundation