Relationships between metabolic syndrome and other baseline factors and the efficacy of ezetimibe/simvastatin and atorvastatin in patients with type 2 diabetes and hypercholesterolemia

Abstract

Objective: To investigate relationships between baseline factors and treatment-associated efficacy changes in type 2 diabetes.

Research design: AND METHODS Multivariable analyses of treatment response in 1,229 type 2 diabetic patients with hypercholesterolemia who received ezetimibe/simvastatin or atorvastatin in a randomized double-blind 6-week study.

Results: Increasing age was related to improvements in all lipid assessments. Men had greater triglyceride and non-HDL cholesterol reductions than women, and black/Hispanic patients had less favorable lipid effects than other races/ethnicities. Increasing baseline LDL cholesterol was associated with improvements in most lipids; higher baseline non-HDL cholesterol with improved HDL cholesterol and triglycerides; higher baseline HDL cholesterol with greater non-HDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) reductions; and higher baseline hs-CRP with smaller LDL cholesterol, non-HDL cholesterol, and apolipoprotein B reductions. Patients with high baseline non-HDL cholesterol or triglycerides less frequently attained LDL cholesterol targets. Obesity was inversely related to HDL cholesterol and hs-CRP changes, and higher baseline A1C to smaller apolipoprotein B reductions. Metabolic syndrome was not a significant predictor.

Conclusions: Treatment responses in type 2 diabetic patients were related to baseline factors, although treatment effects (ezetimibe/simvastatin being more effective than atorvastatin) remained consistent. The presence of predictive factors should be considered in planning lipid-altering therapy.

Figure 1

Multivariable association of categorical factors with the percent change from baseline in LDL cholesterol (LDL-C) (A), HDL cholesterol (HDL-C) (B), non–HDL cholesterol (C), and apolipoprotein B (D). P values (*P < 0.05, **P < 0.01, ***P < 0.001) in A–D correspond to the significance of marked (*) category compared with lowest category for the variable. Association (logistic regression) of categorical factors with the attainment of LDL cholesterol <2.59 mmol/l (<100 mg/dl) (E) and <1.81 mmol/l (<70 mg/dl) (F) is shown. (Note: When non-HDL cholesterol was removed from the multivariable model, baseline LDL cholesterol was a significant factor for attainment of these LDL cholesterol levels, presumably because of the high correlation [r = 0.90] of baseline non-HDL cholesterol with baseline LDL cholesterol levels.) G and H: Proportion of patients who attained LDL cholesterol <1.81 mmol/l (<70 mg/dl) by the number of positive predictive factors in the multivariate model. The four baseline factors associated with LDL cholesterol <1.81 mmol/l, i.e., age ≥65 years, baseline triglycerides <1.70 mmol/l (<150 mg/dl), baseline non-HDL cholesterol <4.14 mmol/l (160 mg/dl), and race/ethnicity other than black or Hispanic, are shown in G. The four baseline factors additionally with ezetimibe/simvastatin (vs. atorvastatin) treatment are shown in H. n = the number of patients with the indicated number of positive factors in the category of all patients assessed for that number. To convert mmol/l to mg/dl, divide by 0.0259. BL, baseline. TG, triglyceride.