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

Abstract

Objective This secondary analysis from the Stop Atherosclerosis in Native Diabetics Study examines the effects of lowering low-density lipoprotein cholesterol (LDL-C) with statins alone versus statins plus ezetimibe (E) on common carotid artery intimal medial thickness (CIMT) in patients with type 2 diabetes and no prior cardiovascular event. Background It is unknown whether the addition of E to statin therapy affects subclinical atherosclerosis. Methods Within an aggressive group (target LDL-C ≤70mg/dL; non-high-density lipoprotein [non-HDL]-C ≤<100 mg/dL; systolic blood pressure [SBP] ≤115mmHg), change in CIMT over 36mos was compared in diabetic individuals >40 yrs receiving statins plus E versus statins alone. CIMT changes in both aggressive subgroups were compared with changes in the standard subgroups (target LDL-C ≤<100mg/dL; non-HDL-C ≤ 130 mg/dL; SBP ≤130mmHg). Results Mean (95%CI) LDL-C was reduced by 31 (23, 37)mg/dL and 32 (27, 38)mg/dL in the aggressive group receiving statins plus E and statins alone, respectively, compared with changes of 1 (−3, 6) mg/dL in the standard group (p<0.0001 vs both aggressive subgroups. Within the aggressive group, mean IMT at 36mos regressed from baseline similarly in the E (−.025 [−05,.003] mm) and non-E subgroups (−.012 [−.03,.008] mm) but progressed in the standard treatment arm (0.039 [0.02, 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 E. CIMT increased in those achieving standard targets.

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

“…Other therapies with complementary but differing mechanisms of action have the potential to benefit endothelial function. In T2D patients, aggressive LDLcholesterol lowering with statins alone or statins plus ezetimibe achieved a similar regression of CIMT in patients who had equivalent LDLcholesterol reductions [236], but comparative therapeutic effects on endothelial function were not studied. Omega-3 fatty acid supplementation has been shown to improve endothelial function in T2D [153,[156][157][158][159], including postprandial endothelial function [156][157][158].…”

Atherogenic Dyslipidemia and Combination Pharmacotherapy in Diabetes: Recent Clinical Trials

“…In T2D patients, combination ezetimibe with lower-dose statin therapy achieved LDL-cholesterol and non-HDLcholesterol targets more effectively than statin alone [98]. In the Stop Atherosclerosis in Native Diabetes Study (SANDS), lowering of LDLcholesterol to aggressive targets with ezetimibe plus statin, or statin alone, achieved regression of carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis, in T2D patients [99]. This related to the reduction in LDLcholesterol and not the minimal changes in triglycerides or HDL-cholesterol [99].…”

“…In the Stop Atherosclerosis in Native Diabetes Study (SANDS), lowering of LDLcholesterol to aggressive targets with ezetimibe plus statin, or statin alone, achieved regression of carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis, in T2D patients [99]. This related to the reduction in LDLcholesterol and not the minimal changes in triglycerides or HDL-cholesterol [99]. Hence, further evidence is required to support the role of ezetimibe in treating residual CVD risk in statintreated T2D patients.…”

Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in Acute Coronary Syndrome

“…8 In a recent randomized study, Tsujita et al demonstrated the superiority of the combination of ezetimibe and statin on coronary atherosclerosis, compared with statin alone, in patients with coronary artery disease. 9 Similarly, the SANDS clinical trial concluded that the beneficial effects of the combination of ezetimibe plus statin on carotid atherosclerosis was similar to that of statin alone in patients with similar reduction in LDL-C. 10 Other clinical trials on the combination of ezetimibe and statin on carotid atherosclerosis, however, noted variable results: both beneficial 10 and non-favorable outcomes. 11,12 Thus, the anti-atherosclerotic effects of ezetimibe remain controversial.…”