Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial

J Am Coll Cardiol. 2008 Dec 16;52(25):2198-205. doi: 10.1016/j.jacc.2008.10.031.

Abstract

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 <or=70 mg/dl; non-high-density lipoprotein cholesterol <or=100 mg/dl; systolic blood pressure <or=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 <or=100 mg/dl; non-high-density lipoprotein cholesterol <or=130 mg/dl; systolic blood pressure <or=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).

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / therapeutic use
  • Azetidines / therapeutic use*
  • Biomarkers / blood
  • Carotid Artery Diseases / drug therapy*
  • Carotid Artery Diseases / pathology
  • Carotid Artery, Common / drug effects*
  • Carotid Artery, Common / pathology
  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / drug effects
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / pathology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / pathology
  • Disease Progression
  • Drug Therapy, Combination
  • Ezetimibe
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Linear Models
  • Male
  • Middle Aged
  • Prospective Studies
  • Severity of Illness Index
  • Tunica Intima / drug effects
  • Tunica Media / drug effects

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ezetimibe

Associated data

  • ClinicalTrials.gov/NCT00047424