Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma

Long-term effects of pravastatin and probucol on serum cholesteryl ester tr ansfer protein (CETP) and xanthoma/xanthelasma size were compared. Twenty-t hree patients with primary hypercholesterolemia and xanthoma/xanthelasma, i ncluding 11 patients with heterozygous familial hypercholesterolemia, were treated with pravastatin (20 mg/day) or probucol (1000 mg/day) for 24 month s. Serum CETP levels were measured by sandwich ELISA. In 11 patients (six m en and five women, 55 +/- 2 [SE] yr) treated with pravastatin, serum choles terol levels decreased from 262 +/- 13 to 229 +/- 13 mg/dl during the 24-mo nth treatment period (P = 0.05). Serum HDL cholesterol levels were not chan ged. Serum CETP levels decreased from 2.5 +/- 0.2 to 2.0 +/- 0.2 mu g/ml (- 21%, P = 0.002). By contrast, in 12 patients (four men and eight women, 57 +/- 4 year) treated with probucol, serum cholesterol levels did not signif icantly decrease from 236 +/- 11 to 207 +/- 13 mg/dl. Serum HDL cholesterol levels decreased from 44 +/- 2 to 30 +/- 2 mg/dl (P = 0.009). Serum CETP l evels increased from 2.3 +/- 0.1 to 2.8 +/- 0.2 mu g/ml (+ 23%, P = 0.02), Xanthelasma regression was found in two of four patients (50%) each treated with pravastatin and probucol, respectively. In contrast, Achilles' tendon xanthoma regressed in four of five patients (80%) treated with pravastatin , but only in two of five patients (40%) treated with probucol. Patients wi th xanthoma/xanthelasma regression after 2 years treatment had higher basel ine levels of serum CETP than those without regression (2.7 +/- 0.2 mu g/ml [n = 9] versus 2.1 +/- 0.2 mu g/ml [n = 7], P = 0.05), Serial changes in s erum CETP levels during treatment with pravastatin and probucol were discor dant, but not related to the degree of xanthoma regression. However, higher level of serum HDL3 cholesterol was an independent factor in the smaller s ize of Achilles' tendon xanthoma at baseline. In addition, higher levels of serum HDL3 triglyceride on lipid-lowering therapy (6 months) appear to be a common predictor of regression of Achilles' tendon xanthoma in the treatm ent with either pravastatin or probucol. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.