Long-term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia.

To assess the long-term efficacy and use of fenofibrate together with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor ("statin") in the treatment of elevated levels of triglycerides and low-density lipoprotein (LDL) cholesterol, we conducted a study that compared a before- and after-case series. The study involved 80 patients with a diagnosis of combined hyperlipidemia and existing coronary artery disease (81% of patients) or outpatients with > or = 3 risk factors for coronary artery disease who had been receiving treatment at a tertiary care center. Fasting biochemical measures were obtained at baseline during monotherapy with a statin consisting of pravastatin 20 mg once daily or simvastatin 10 mg once daily (39 patients) or fenofibrate 300 mg once daily (41 patients), and during a 2-year period of combination therapy. This combination therapy comprised fenofibrate 300 mg once daily or micronized fenofibrate 200 mg once daily taken together with pravastatin 20 mg once daily (63 patients) or simvastatin 10 mg once daily (17 patients). The main outcome measures were: (1) absolute and percent change in total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol; (2) percentage of patients with alanine aminotransferase > or = 2x the upper limits of normal on any occasion; (3) percentage of patients with creatinine kinase > or = 3 times the upper limits of normal on any occasion; (4) absolute changes in alanine aminotransferase and creatinine phosphokinase; and (5) months on combination therapy. Patients receiving combination therapy had a mean total cholesterol (+/- standard error of the mean [SEM]) that was significantly decreased by 26+/-1%, triglycerides by 41+/-3%, and LDL cholesterol by 28+/-2%, and mean HDL cholesterol that was significantly increased by 22+/-6%. These changes correspond to mean absolute changes of total cholesterol: -75+/-5 mg/dL; triglycerides: -94+/-13 mg/dL; LDL cholesterol: -52+/-5 mg/dL; and HDL cholesterol: 5+/-1 mg/dL. During combination treatment, alanine aminotransferase increased by 2+/-2 U/liter (not significant) and creatinine phosphokinase decreased by 4+/-13 U/liter (not significant). During treatment, 8 patients (10%) had transitory isolated elevations in alanine aminotransferase levels > or = 2 times the upper limits of normal and 2 patients (2.5%) had an isolated and transitory elevation of creatinine kinase (> or = 3x but < 6x upper limits of normal) without associated muscle symptoms. Patient-years on combination therapy equaled 220.6 (average 2.06 years per patient). The results demonstrated that combination treatment with fenofibrate and low-dose simvastatin or pravastatin is generally safe and effective for the treatment of combined hyperlipidemia in patients with normal hepatic and renal function.