Study Design, Rationale, and Baseline Characteristics: Evaluation of Fenofibric Acid on Carotid Intima-Media Thickness in Patients with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) Trial

Purpose

Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels contribute to cardiovascular disease risk and can be effectively treated with fenofibric acid. A trial is under way to evaluate the effect of once-daily fenofibric acid or placebo on carotid intima-media thickness (CIMT) progression in patients with controlled low-density lipoprotein cholesterol (LDL-C) levels achieved through atorvastatin treatment, but with high TG and low HDL-C levels.

Methods

In this multicenter, double-blind study, 682 patients were randomized to once-daily delayed-release capsules of choline fenofibrate 135?mg (fenofibric acid Trilipix?; Abbott, North Chicago, IL]) or placebo plus atorvastatin treatment after a 2- to 10-week diet and atorvastatin run-in period. Key inclusion criteria included age ≥45?years; posterior-wall common CIMT ≥0.7?mm on at least one side at baseline; fasting results of TG ≥150?mg/dL, and HDL-C ≤45?mg/dL for men or HDL-C ≤55?mg/dL for women at screening while receiving atorvastatin; controlled LDL-C; and known coronary heart disease (CHD) or a CHD risk equivalent. The primary efficacy variable is the rate of change from baseline through week 104 in the mean posterior-wall intima-media thickness of the common carotid arteries (composite value of left and right sides).

Conclusions

This trial is the first to examine the effect of fenofibric acid on CIMT and the first CIMT trial to select patients with controlled LDL-C and elevated TG and low HDL-C as inclusion criteria. Also, this trial will prospectively evaluate the effect of treatment on LDL particles and address shortcomings of previous CIMT trials.