Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (The SAFARI Trial)

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 greater than or equal to150 and less than or equal to500 mg/dl, and LDL cholesterol > 130 mg/dl) received simvastatin monotherapy (20 mg/day, h = 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. (C) 2005 by Excerpta Medica Inc.