Ezetimibe plus simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study)

Background: The primary goal of therapy in patients with hypercholesterolemia and coronary heart disease (CHD) is reducing low-density lipoprotein cholesterol (LDL-C). This was a multicenter, randomized, double-blind, double-dummy study in patients with type 2 diabetes mellitus (T2DM). Methods: Adult patients with T2DM and CHD (N = 93) on a stable dose of simvastatin 20 mg with LDL-C >= 2.6 mmol/L (100 mg/dL) and <= 4.1 mmol/L (160 mg/dL) were randomized to ezetimibe 10 mg plus simvastatin 20 mg (EZ + simva 10/20 mg) or simvastatin 40 mg for 6 weeks. Percent change in LDL-C, high-density lipoprotein cholesterol, and triglycerides was assessed. Results: EZ + simva 10/20 mg produced a significantly greater change from treated baseline compared with simvastatin 40 mg in LDL-C (-32.2% vs -20.8%; p < 0.01) and total cholesterol (-20.6% vs -13.2%; p < 0.01). A greater proportion of patients achieved LDL-C < 2.6 mmol/L with EZ + simva 10/20 mg than with simvastatin 40 mg, but this was not statistically significant (78.4% vs 60%; odds ratio = 2.81; p = 0.052). Changes in high-density lipoprotein cholesterol and triglycerides were similar between treatments. Both treatments were generally well-tolerated. Conclusions: These results demonstrate that EZ + simva 10/20 mg may provide a superior alternative for LDL-C lowering vs doubling the dose of simvastatin to 40 mg in hyperlipidemic patients with T2DM and CHD. In addition, the combination therapy may provide an alternative treatment for patients who require further LDL-C reduction than they can achieve with simvastatin 20 mg alone.