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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia.

PURPOSE: To compare the efficacy and safety of pravastatin, gemfibrozil, combined therapy, and placebo in the treatment of hypercholesterolemia. PATIENTS AND METHODS: At 5 centers in Sweden and 2 in Finland, 290 ambulatory patients were randomized to active treatment or placebo for 12 weeks following a single-blind placebo lead-in period. The study was double-blind and placebo-controlled. Patients has plasma total cholesterol levels of at least 6.0 mmol/L or in the 90th percentile by age and sex and triglycerides less than 4.0 mmol/L. Concentrations of lipids, lipoproteins, and apolipoproteins were measured, and clinical laboratory tests included liver function and creatine kinase determinations. RESULTS: Pravastatin reduced total cholesterol (26.3% versus 15.2%, p < or = 0.01), low-density lipoprotein cholesterol (LDL-C) (33.5% versus 16.8%, p < or = 0.01), and apolipoprotein B (28.8% versus 15.3%, p < or = 0.01) more than gemfibrozil. Gemfibrozil reduced very-low-density lipoprotein cholesterol (VLDL-C) (49.1% versus 21.9%, p < or = 0.01) and triglycerides (42.2% versus 14.2%, p < or = 0.01) and increased high-density lipoprotein cholesterol (HDL-C) (15.2% versus 5.9%, p < or = 0.01) more than pravastatin. Pravastatin and gemfibrozil increased apolipoprotein A-I comparably (3.3% versus 5.0%, p = NS). The combination significantly (p < or = 0.01) reduced total cholesterol (29.0%), LDL-C (37.1%), VLDL-C (49.4%), and apolipoprotein B (31.6%), and increased HDL-C (16.8%). The combination reduced the total cholesterol/HDL-C (39.3%) and LDL-C/HDL-C (45.8%) ratios significantly (p < 0.01). Adverse events and clinical laboratory abnormalities were generally mild and transient in all groups, although creatine kinase tended to be higher with combination therapy. Study drugs were withdrawn from two patients with asymptomatic creatine kinase elevations. Severe myopathy was not observed; however, the presence of subclinical musculoskeletal effects cannot be excluded. CONCLUSIONS: Co-administration of pravastatin and gemfibrozil combined the specific effects of the two drugs on lipoprotein concentrations and ratios. The incidence of side effects was low; severe myopathy did not occur. The combination may be useful in selected cases of combined hyperlipidemia; however, since myopathy at a low incidence or after long-term therapy cannot be excluded, the routine use of combination therapy is not advisable.[1]


  1. Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia. Wiklund, O., Angelin, B., Bergman, M., Berglund, L., Bondjers, G., Carlsson, A., Lindén, T., Miettinen, T., Odman, B., Olofsson, S.O. Am. J. Med. (1993) [Pubmed]
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