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EXPEDITED PUBLICATION

Effect of Statins Alone Versus Statins Plus Ezetimibe on Carotid Atherosclerosis in Type 2 Diabetes

The SANDS (Stop Atherosclerosis in Native Diabetics Study) Trial

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^_**

^_* National Heart, Lung, and Blood Institute, Bethesda, Maryland
MedStar Research Institute, Hyattsville, Maryland
Weill Cornell Medical College, New York, New York
University of Arizona Health Science Center, Tucson, Arizona
^|| Black Hills Center for American Indian Health, Rapid City, South Dakota
^¶ University of Maryland School of Medicine, Baltimore, Maryland
^# Phoenix Indian Medical Center, Phoenix, Arizona
^_** Washington Hospital Center, Washington, DC

Manuscript received August 28, 2008; revised manuscript received October 8, 2008, accepted October 14, 2008.

^_* Reprint requests and correspondence: Dr. Wm. James Howard, MedStar Research Institute, 6495 New Hampshire Avenue, Hyattsville, Maryland 20783 (Email: wm.james.howard{at}medstar.net).

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 [ClinicalTrials.gov] )

Key Words: ezetimibe • carotid artery intima-media thickness • atherosclerosis

Abbreviations and Acronyms   BP = blood pressure   CIMT = common carotid artery intima-media thickness   CV = cardiovascular   HDL-C = high-density lipoprotein cholesterol   LDL-C = low-density lipoprotein cholesterol   SBP = systolic blood pressure

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