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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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1
Lipid Clinic of Cardiovascular Associates of Northern Wisconsin, Wausau 54401, USA.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
10385779
DOI:
10.1016/s0002-8703(99)70261-9
[Indexed for MEDLINE]

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