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

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).

Figure 1. SANDS Participant Flow Diagram

CVD = cardiovascular disease IMT = intimal medial thickness LDL-C = low-density lipoprotein cholesterol SBP = systolic blood pressure TG = triglyceride

Figure 2. Categorical Change in Carotid Intimal Medial Thickness in SANDS Subgroups

Numbers represent percentages of participants who experienced a decrease or no change in CIMT greater than 0.01mm versus an increase. The majority of both aggressive subgroups experienced a decline or no change in IMT, whereas the majority of the standard group showed an increase, p<0.0001. E+ = statin plus ezetimibe; E− = statin alone