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Am Heart J. 1999 Jul;138(1 Pt 1):151-5.

Long-term safety and efficacy of combination gemfibrozil and HMG-CoA reductase inhibitors for the treatment of mixed lipid disorders.

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Lipid Clinic of Cardiovascular Associates of Northern Wisconsin, Wausau 54401, USA.



Combinations of gemfibrozil and a 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase inhibitor show promise in treating mixed lipid abnormalities. However, concern regarding the risk of myopathy and hepatic toxicity has limited the use of this combination. To determine the long-term safety and efficacy of this combination, we prospectively identified all patients placed on a combination of gemfibrozil and any HMG reductase inhibitor.


Pravastatin, simvastatin, fluvastatin, lovastatin, or atorvastatin at incremental doses was combined with gemfibrozil (600 mg twice daily). Lipid profiles, creatine kinase levels, and aminotransferase levels were monitored. Two hundred fifty-two patients with established atherosclerosis receiving combination therapy for a mean of 2.36 +/- 1.52 years spanning a total of 593.6 patient-years were monitored.


In 148 patients, gemfibrozil was started before an HMG was added. The pretreatment total cholesterol level fell from 222 +/- 34 mg/dL to 181 +/- 26 mg/dL (P <.001) on combination therapy. HDL cholesterol level rose from 30 +/- 5 mg/dL to 36 +/- 7 mg/dL (P <.01), triglyceride level fell from 361 +/- 141 mg/dL to 212 +/- 101 mg/dL (P <.03). The ratio of total cholesterol to HDL fell from 7.6 +/- 1. 7 to 5.3 +/- 1.6 (P <.001). In 104 patients an HMG was begun before gemfibrozil was added. Pretreatment total cholesterol level fell from 246 +/- 54 mg/dL to 192 +/- 40 mg/dL on combination therapy (P <.01). HDL level rose from 33 +/- 9 mg/dL to 38 +/- 9 mg/dL (P <.03) and triglyceride level fell from 314 +/- 183 mg/dL to 183 +/- 93 mg/dL (P <.001). The ratio of total cholesterol to HDL fell from 7.9 +/- 3.6 to 5.2 +/- 1.4 (P <.001). In both groups the lipid profile on combination therapy was significantly better than that obtained on single-agent therapy. One episode of myopathy (0.4%) and one episode of aminotransferase level elevation (0.4%) of greater than 3 times upper limit of normal occurred. Both resolved with cessation of therapy without consequence.


Combinations of gemfibrozil and an HMG, compared with either agent alone, results in improved long-term control of lipid abnormalities in mixed lipid disorders. The low incidence of toxicity permits the use of combination therapy in patients at high risk of atherosclerotic complications.

[Indexed for MEDLINE]

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