Long-term safety and efficacy of fenofibrate/pravastatin combination therapy in high risk patients with mixed hyperlipidemia not controlled by pravastatin monotherapy

OBJECTIVE: To assess the long-term safety and efficacy of a fenofibrate/pravastatin 160/40 mg fixed-dose combination in high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy. STUDY DESIGN AND METHODS: After an 8-week pravastatin 40 mg and diet run-in period, high-risk patients (n = 248) with low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and triglycerides (TG) ≥ 150 and ≤400 mg/dL, were randomized to fenofibrate/pravastatin combination therapy or to pravastatin monotherapy for 12 weeks, followed by an open-label, 52-week safety phase on the combination therapy. RESULTS: Of the 224 patients who continued after the double-blind phase, 211 completed the one-year safety period. Overall, fenofibrate/pravastatin combination therapy was well tolerated during this extension study. Only three patients had an elevation of ALAT > 3 times the upper limit of normal and one patient a CPK elevation ≥5, but <10 times the upper limit of normal. At week 64, and by comparison to baseline levels on pravastatin 40 mg, the fenofibrate/pravastatin combination therapy significantly reduced non-high-density lipoprotein (non-HDL) cholesterol by 16.3%, LDL-C by 12.2%, TG by 31.6%, apolipoprotein B by 11.0% and increased HDL-cholesterol and apolipoprotein A1 respectively by 4.8 and 9.6% (p < 0.0001 for all the variables). A limitation of this trial is that the study was not powered to assess clinical events. CONCLUSIONS: Long-term co-administration of fenofibrate/pravastatin 160/40 mg in a single capsule was well tolerated and produced complementary benefits on the overall lipid profile of high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg.