Patients with combined
hyperlipidemia (elevated
triglyceride [TG] levels, elevated
low-density lipoprotein [
LDL] cholesterol, and multiple
lipoprotein abnormalities) are at increased risk for
coronary heart disease. We conducted a multicenter (in the United States), randomized, double-blind, active-controlled, 18-week study to determine if combination
therapy with
simvastatin plus
fenofibrate is more effective in reducing elevated TG levels, thus improving the
lipoprotein pattern in patients with combined
hyperlipidemia compared with
simvastatin monotherapy, and to evaluate safety and tolerability. Patients (aged 21 to 68 years) with a diagnosis of combined
hyperlipidemia (fasting TG levels >/=150 and </=500 mg/dl, and
LDL cholesterol >130 mg/dl) received
simvastatin monotherapy (20 mg/day, n = 207) or
simvastatin 20 mg plus
fenofibrate (160 mg/day) combination
therapy (n = 411) for 12 weeks following a 6-week diet and placebo run-in period. From baseline to week 12, median TG levels decreased 43.0% (combination
therapy) and 20.1% (
simvastatin monotherapy [treatment difference -23.6%, p <0.001]). Mean
LDL cholesterol levels decreased 31.2% and 25.8% (treatment difference -5.4%, p <0.001), and
high-density lipoprotein cholesterol levels increased 18.6% and 9.7% (treatment difference 8.8%, p <0.001) in the combination
therapy versus monotherapy groups, respectively. No drug-related serious adverse experiences were observed. No patient experienced clinical
myopathy or severe abnormalities in liver function. Combination
therapy with
simvastatin 20 mg and
fenofibrate 160 mg in patients with combined
hyperlipidemia resulted in additional improvement in all
lipoprotein parameters measured compared with
simvastatin 20 mg monotherapy and was well tolerated. Thus, this combination
therapy is a beneficial therapeutic option for managing combined
hyperlipidemia.