Jerome L. Fleg, Mihriye Mete, Barbara V. Howard, Jason G. Umans, Mary J. Roman, Robert E. Ratner, Angela Silverman, James M. Galloway, Jeffrey A. Henderson, Matthew R. Weir, Charlton Wilson, Mario Stylianou, and Wm. James Howard

Effect of Statins Alone Versus Statins Plus Ezetimibe on Carotid Atherosclerosis in Type 2 Diabetes
The SANDS (Stop Atherosclerosis in Native Diabetics Study) Trial

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])