The primary complication of type 2 diabetes is macrovascular disease. Eighty percent of diabetes patients will develop macrovascular disease or die from it. These events can be reduced by decreasing the risk factors for macrovascular disease, such as hyperlipidemia. Numerous studies have shown that HMG-CoA reductase inhibitors (statins) can reduce cardiovascular events. Combination lipid therapy has been shown to decrease LDL-Cholesterol (LDL-C) and triglyceride (TG) levels to a greater degree than a single agent. It is not known whether this increased reduction results in a greater decrease in cardiovascular events.1
In the randomized trial conducted by the ACCORD study group,2 researchers examined the effects of combination lipid therapy in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. Participants needed to have a glycated hemoglobin (Hgb A1c) level of 7.5% or more, be between the ages of 40 and 79 years and have cardiovascular disease, or be between the ages of 55 and 79 years and have anatomical evidence of significant atherosclerosis, albuminuria, left ventricular hypertrophy, or at least two additional risk factors for cardiovascular disease such as dyslipidemia, hypertension, current status as a smoker, or obesity. Additionally, participants needed an LDL-C between 60 and 180 mg/dL, HDL-Cholesterol (HDL-C) less than 55 mg/dL for women and African Americans, or less than 50 for all other groups, and TG less than 750 mg/dL if not on a lipid medication or less than 400 if on a lipid medication.
In the ACCORD patients on simvastatin monotherapy were compared with those on simvastatin and fenofibrate. The primary composite outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The secondary end points included expanded macrovascular outcomes, major coronary artery disease events, nonfatal myocardial infarction, total stroke, nonfatal stroke, total mortality, cardiovascular mortality, and congestive heart failure. The final analysis included 5518 patients with type 2 diabetes mellitus. These patients had a mean age of 62 years old, a mean Hgb A1c of 8.3%, a mean LDL-C of 101 mg/dL, a mean HDL-C of 38 mg/dl and a median plasma triglycerides of 162 mg/dL.
During the mean 4.7 year follow-up period, the mean LDL-C fell from 100.0 to 81.1 mg/dL in the fenofibrate + simvastatin group and from 101.1 to 80.0 mg/dL in the simvastatin monotherapy group. The mean HLD-C levels increased from 38.0 to 41.2 mg/dL and from 38.2 to 40.5 mg/dL respectively. Median TG levels fell from 164 to 122 mg/dL with combination therapy compared to 160 to 144 mg/dL with statin monotherapy. The primary outcome occurred in 291 patients (10.5%) in the statin + fenofibrate group compared with 310 (11.3%) in the statin monotherapy group (p=0.32). The hazard ratio showed no statistically significant decrease in cardiovascular events between patients on statin monotherapy versus those receiving a stain plus fenofibrate [hazard ratio [HR], 0.92; 95% confidence interval [CI] 0.79 to 1.08].