The effect of simvastatin on triglyceride-rich lipoproteins in patients with type 2 diabetic dyslipidemia: a SILHOUETTE trial sub-study.

Objective: To determine if simvastatin effectively decreases the elevated levels of triglyceride (TG), TG-rich lipoproteins, and small, dense LDL particles, which are characteristic of diabetic dyslipidemia. Research design and methods: We conducted a prespecified analysis from a double-blind, placebo-controlled, randomized, 6-week crossover trial in patients with type 2 diabetes and low HDL-C (less than 40 mg/dL). Each patient was randomized to 1 of 6 possible treatment arms; each patient received simvastatin 80 mg, simvastatin 40 mg, and placebo over 3 periods. We used the validated vertical auto profile (VAP dagger) method to directly assess TG-rich lipoproteins and LDL subclasses. We assessed the efficacy of simvastatin to improve the lipoprotein profile in adult men (71%) and women (29%) (n = 151) with stable type 2 diabetes (HbA(1c) < 9%), LDL-C > 100 mg/dL, HDL-C < 40 mg/dL, and fasting TG level > 150 and < 700 mg/dL (median = 273 mg/dL). Main outcome measures: Percentage change from baseline in LDL and VLDL (TG-rich lipoproteins), LDL subclasses, and additional lipoproteins at the end of each 6-week treatment interval; percentage of patients who reached NCEP ATP III non-HDL goal of < 130 mg/dL by the end of each 6-week period. Results: Both simvastatin 80 mg and 40 mg significantly reduced VLDL-C, VLDL3, and IDL, as well as the four LDL subclasses measured with VAP, compared with placebo. Simvastatin 80 mg, compared with simvastatin 40mg, provided additional efficacy. With simvastatin 80 mg, 77.2% of patients not at their non-HDL-C goal of < 130mg/dL at study baseline reached goal, compared with 65.7% following simvastatin 40mg treatment, and 2.2% following placebo. Conclusions: Treatment with simvastatin effectively reduced the elevated levels of TG-rich lipoproteins and improved LDL composition in patients with type 2 diabetes. A large percentage of these patients attained the NCEP ATP III non-HDL-C goal of < 130 mg/dL, which demonstrates the improvement of the atherogenic profile in these patients.