Clofibrate-induced low density liporotein elevation. Therapeutic implications and treatment by colestipol resin.
Plasma lipid and lipoprotein responses to clofibrate were assessed in fifteen hypertriglyceridemic patients for the purpose of ascertaining low-density lipoprotein (LDL) changes. Subjects were grouped into either Type IV (11) or IIB (4) subgroups according to initial LDL level. Clofibrate was without effect on LDL in the IIB group, but consistent, often large, elevations were noted in Type IV cases (mean increase, 37.6%, P less than 0.001). In the IIB subgroup, addition of the bile-acid sequestrant, colestipol, lowered LDL (27.8%, P less 0.02) and total cholesterol (21.3%, P less 0.01) below pre-treatment values. In the Type IV subgroup, LDL fell to 19.5% above baseline (P great than 0.05). Significant LDL elevations induced by clofibrate in three of six subjects were restored to initial levels. In both groups, triglycerides and very-low density lipoproteins (VLDL) were not affected. The efficacy of colestipol in reducing LDL levels, expressed as either absolute or percentage reductions, increased as a function of increasing post-clofibrate LDL concentration (r = 0.84, P less than 0.001). In these subjects the level of LDL after treatment with clofibrate depended upon their LDL level prior to drug therapy, the effect of clofibrate on this level, and lipoprotein phenotype. Thus colestipol was most effective in IIB subjects, Type IV subjects with the lowest baseline VLDL and hence reciprocally highest LDL, and Type IV individuals who exhibited the largest LDL induction by clofibrate. The reported ineffectiveness of clofibrate on mortality and morbidity in patients with established coronary heart disease might be related to elevations and infrequent reductions of LDL. From the perspective of lipoprotein lowering, the combination with colestipol appears more favorable.
D000328:Adult; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D003084:Colestipol / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011073:Polyamines; D014280:Triglycerides; D002784:Cholesterol; D002994:Clofibrate; D003084:Colestipol