TREATMENT OF COMBINED HYPERLIPIDEMIA WITH FLUVASTATIN AND GEMFIBROZIL, ALONE OR IN COMBINATION, DOES NOT INDUCE MUSCLE DAMAGE

Although combination therapy using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co-A) reductase inhibitors and fibrates is efficacious in comb ined hyperlipidemia, such treatment has been associated with myopathy. For this reason, we studied the effects of fluvastatin and gemfibrozi l, alone or in combination, on muscle. A total of 21 patients with com bined hyperlipidemia were recruited who were matched for age, body mas s index, and baseline levels of total cholesterol, low density lipopro tein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) , triglycerides, creatine phosphokinase, and myoglobin. Patients were randomized to three groups for 6-week treatment with fluvastatin at 40 mg/day, gemfibrozil at 600 mg twice daily, or a combination of the tw o drugs. Parameters for muscle damage were rises in levels of serum cr eatine phosphokinase and myoglobin compared with pre-exercise levels; these were assessed 1 hr and 8 hr after a 45 min lean body mass standa rdized ergometer test, which was performed before and after treatment in all patients. Biopsies from the quadriceps muscle were taken 48 hr after each test. Fluvastatin lowered total cholesterol and LDL-C by 23 % and 35%, respectively (p <0.01), with no effects on triglycerides an d HDL-C. Gemfibrozil lowered triglycerides by 40% (p <0.01) but did no t lower total cholesterol or LDL-C significantly. The combination ther apy decreased total cholesterol LDL-C, and triglycerides by 28%, 29%, and 39%, respectively (p <0.05). Pre-exercise creatine phosphokinase a nd myoglobin levels were not affected by treatment in any group. The m ean +/- SEM peak creatine phosphokinase rise (8 hr after exercise) did not differ significantly before or after treatment with fluvastatin o r combination therapy, but was reduced after treatment with gemfibrozi l (43.3 +/- 13.8 vs 23.0 +/- 6.9 U/liter; p <0.05). Peak myoglobin ris e (1 hr after exercise) was similar before and after treatment with fl uvastatin and gemfibrozil, but was lower after combination therapy. Tw o patients had abnormal muscle histology (atrophy of type 2 fibers) be fore therapy, whereas after treatment only 1 patient taking fluvastati n and 1 taking gemfibrozil had abnormal histology. In conclusion, 8-we ek combination therapy with fluvastatin plus gemfibrozil is effective in patients with combined hyperlipidemia and has no adverse effects on muscle.