Atherosclerosis 145 (1999) 405 – 413 Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma Akihiro Inazu a,b, *, Junji Koizumi c , Kouji Kajinami a , Tsuyoshi Kiyohar a,d , Kenji Chichibu d , Hiroshi Mabuchi a a The Second Department of Internal Medicine, School of Medicine, Kanazawa Uniersity, Takara -machi 13 -1, Kanazawa 920 -8641, Japan b Department of Clinical Laboratory Science, School of Health Sciences, Kanazawa Uniersity, Kodatsuno 5 -11 -80, Kanazawa 920-0942, Japan c Department of General Medicine, Kanazawa Uniersity Hospital, Takara -machi 13 -1, Kanazawa 920 -8641, Japan d Diagnostic Laboratory, Diagnostics Research Labs, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan Received 21 May 1998; received in revised form 11 December 1998; accepted 22 February 1999 Abstract Long-term effects of pravastatin and probucol on serum cholesteryl ester transfer protein (CETP) and xanthoma/xanthelasma size were compared. Twenty-three patients with primary hypercholesterolemia and xanthoma/xanthelasma, including 11 patients with heterozygous familial hypercholesterolemia, were treated with pravastatin (20 mg/day) or probucol (1000 mg/day) for 24 months. Serum CETP levels were measured by sandwich ELISA. In 11 patients (six men and five women, 55 2 [SE] yr) treated with pravastatin, serum cholesterol levels decreased from 262 13 to 229 13 mg/dl during the 24-month treatment period (P =0.05). Serum HDL cholesterol levels were not changed. Serum CETP levels decreased from 2.5 0.2 to 2.0 0.2 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 significantly 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 levels increased from 2.3 0.1 to 2.8 0.2 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 with xanthoma/xanthelasma regression after 2 years treatment had higher baseline levels of serum CETP than those without regression (2.7 0.2 g/ml [n =9] versus 2.1 0.2 g/ml [n =7], P =0.05). Serial changes in serum CETP levels during treatment with pravastatin and probucol were discordant, but not related to the degree of xanthoma regression. However, higher level of serum HDL3 cholesterol was an independent factor in the smaller size 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 treatment with either pravastatin or probucol. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Pravastatin; Probucol; High density lipoprotein; Cholesteryl ester transfer protein; Xanthoma; Regression www.elsevier.com/locate/atherosclerosis 1. Introduction The efficacy of drug therapy for atherosclerosis or xanthoma may be dependent on a specific phenotype through lipid-lowering dependent or independent mech- anisms. One of the underlying mechanisms of prevent- ing atheroma or xanthoma is reverse cholesterol transport, in which excess cholesterol is transported from peripheral tissues to the liver [1]. This process involves several biological activities of cholesterol efflux from peripheral tissues, cholesterol esterification, cholesteryl ester (CE) transfer from HDL to VLDL- LDL, and subsequent receptor-mediated clearance of lipoproteins by the liver or selective uptake of CE without endocytosis of HDL. Serum cholesteryl ester transfer protein (CETP) transfers and exchanges CE * Corresponding author. Tel.: +81-76-265-2251; fax: +81-76-234- 4251. E-mail address: inazua@mhs.mp.kanazawa-u.ac.jp (A. Inazu) 0021-9150/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII:S0021-9150(99)00088-X