Plasma and lipoprotein lipid responses to four hypolipid drugs

The responses of 14 hyperlipidemic subjects to 4 hypolipidemic agents were compared by measureing cholesterol and triglyceride in whole plasma, very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) monthly for 2 months before and 3 months during treatment with each of 4 drugs: clofibrate, 2 g/d; colestipol, 20 g/d; para-aminosalicylic acid-ascorbate (PAS-C), 6–8 g/d; and oxandrolone, 7.5 mg/d. Lipid responses proved to be stable by the first monthly evaluation both off and on each drug. Mean adherence was high and similar for all agents (81–92% of the prescribed dose). Clofibrate was associated with significant decreases in mean plasma cholesterol (−16%, p<.01), plasma triglyceride (−51%, p<.005), VLDL-cholesterol (−61%, p<.005) and VLDL-triglyceride (−61%, P<.005), while HDL cholesterol increased (+20%, p<.01), and the LDL-cholesterol/HDL ratio declined (−24%, p<.05). Colestipol was associated with decreases in mean plasma cholesterol (−15%, p<.01) and LDL-cholesterol (−22%, p<.05), while VLDL-triglyceride increased (+41%, p<.05), and the LDL-cholesterol/HDL-cholesterol ratio declined (−25%, p<.05). PAS-C was associated with decreases in VLDL-cholesterol (−30%, p<.05), and VLDL-triglyceride (−29%, p<.05), while the LDL-cholesterol/HDL-cholesterol ratio remained unchanged. Oxandrolone was associated with increases in mean plasma cholesterol (+7%, p<.05), LDL-cholesterol (+45%, p<.005 [+25% excluding one subject who increased 298%]), and LDL-triglyceride (+24%, p<.01), while decreases occurred in plasma triglyceride (−31%, p<.05), VLDL-cholesterol (−26%, p<.05), VLDL-triglyceride (−42%, p<.005), HDL-cholesterol (−45%, p<.005), and HDL-triglyceride (−43%, p<.01). The mean LDL-cholesterol/HDL-cholesterol ratio increased by 109% (p<.005), reflecting the reciprocal changes in LDL and HDL. Thus, while both clofibrate and colestipol were associated with significant, equivalent reductions in theoretical atherogenic risk, oxandrolone produced a net effect that was not only adverse but 4 times that magnitude, suggesting caution in its long-term use, even for the management of hypertriglyceridemia.