ABSTRACT
Fibric acid derivatives have a mode of action that suggests they may be of value in patients whose serum triglyceride remains elevated despite statin therapy (see Chapter 9). They have little effect in decreasing LDL cholesterol. They do decrease serum cholesterol, but that is due to a reduction in VLDL cholesterol. Their main action is decreasing serum triglycerides (Table 5.6), which leads to a decrease in CETP activity and small dense LDL. The latter effect, though important in explaining the anti-atherogenic effect of fibrates, does not greatly decrease LDL cholesterol, because small dense LDL is already depleted in cholesterol. Fibrates also raise HDL, because they stimulate lipoprotein lipase activity (which partly explains their triglyceride-lowering action) and because of the decrease in CETP activity that they induce. The increase is generally not more that 10%, and though they have been extensively promoted for the treatment of low HDL following the publication of the Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial (VAHIT), their effect would be undetectable in routine clinical practice in most patients with low HDL cholesterol (e.g. in a patient whose HDL cholesterol is 0.9 mmol/l, an increase to 1.0 mmol/l would be almost within the error of the HDL method and biological variation).
