Some Aspects of Sensitivity and Resistance to the Cholesterol Lowering Effect of Clofibrate

Clofibrate (CPIB) is not generally considered the drug of choice in the treatment of familial type II hypercholesterolemia (Levy et al., 1972). This is unfortunate because in our experience (Davignon et al., 1971), and in that of others (Crepaldi et al., 1974), it has been found to be a potent cholesterol and β-lipoprotein cholesterol-lowering agent in a good proportion of patients affected with this disease. The problem, however, is to identify the potential responders among these patients. A few years ago, we were able to demonstrate a negative correlation between the average plasma triglyceride/cholesterol (TG/TC) ratio of a control period and the cholesterol-lowering effect of Clofibrate in familial type II (Davignon et al., 1971). Thus, type IIa patients with low plasma triglycerides were more likely to have their plasma cholesterol concentration lowered by this drug than type IIb patients with higher plasma triglycerides. Since a line arbitrarily drawn at a TG/TC ratio of 0.40 separated the majority of the responders from the majority of the nonresponders, we have been using this ratio in our laboratory as a cutoff point for separating type IIa from type IIb. At one extreme, the responsive type II patient may show a 30% decrease in plasma cholesterol while at the other extreme a 10% increase may be observed. These findings allowed us to account for some of the discrepancies in the literature on the effectiveness of Clofibrate in familial hypercholesterolemia as a function of the relative proportion of types IIa and IIb (or of responders and nonresponders).