Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial.
OBJECTIVE
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).
Fleg
Jerome L
JL
National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Mete
Mihriye
M
Howard
Barbara V
BV
Umans
Jason G
JG
Roman
Mary J
MJ
Ratner
Robert E
RE
Silverman
Angela
A
Galloway
James M
JM
Henderson
Jeffrey A
JA
Weir
Matthew R
MR
Wilson
Charlton
C
Stylianou
Mario
M
Howard
Wm James
WJ
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001384:Azetidines / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D048909:Diabetes Complications / Q000188:drug therapy* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D017539:Tunica Intima / Q000187:drug effects; D017540:Tunica Media / Q000187:drug effects
D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe