Effects of policosanol on the susceptibility of low-density lipoprotein isolated from hypercholesterolemic patients at high coronary risk to in vitro copper-mediated lipid peroxidation: a randomized, double-blind pilot study

Abstract

Objective: The aim of the study was to investigate the effects of policosanol administered at its starting dosage (5 mg/d) on low-density lipoprotein (LDL) peroxidation in patients with type II hypercholesterolemia and high coronary risk. Background: Oxidation of LDL has been suggested as a step in the development of atherosclerosis. Policosanol is a cholesterol-lowering drug that inhibits lipid peroxidation in experimental models and healthy volunteers. Methods: In this randomized, double-blind, placebo-controlled trial, after 6 weeks of dietary stabilization, 20 patients were randomly assigned to receive placebo or policosanol 5-mg tablets once daily for 12 weeks. LDL isolated at baseline and after 12 weeks of therapy was submitted to in vitro copper-catalyzed time-course experiments. Results: The 2 groups were statistically similar at randomization. When compared with baseline, policosanol significantly decreased ( P < 0.05) total cholesterol (TC) by 15.7%, LDL-cholesterol (LDL-C) by 19.6%, the ratio of TC to high-density lipoprotein cholesterol (HDL-C) by 18.1%, and the ratio of LDL-C to HDL-C by 23.2%, whereas it significantly increased ( P < 0.05) HDL-C by 5.4%; the change in triglycerides did not reach statistical significance. When compared with placebo, policosanol significantly decreased TC, the ratio of TC to HDL-C, and the ratio of LDL-C to HDL-C ( P < 0.05), as well as LDL-C ( P < 0.01), whereas it significantly increased HDL-C ( P < 0.05). The percentage of change versus placebo was significant for TC ( P < 0.001), LDL-C ( P < 0.01), HDL-C ( P < 0.05), and the ratios of TC to HDL-C and LDL-C to HDL-C ( P < 0.05). Treatment was safe and well tolerated. No drug-related disturbances in safety indicators were found. Three patients withdrew from the study; however, none withdrew because of adverse experiences. Lag phase was significantly prolonged by 30.9% in the policosanol-treated group compared with baseline values (58.87 ± 19.12 vs 51.68 ± 18.33 min, respectively; P < 0.05). In contrast, no significant changes were found in the lipid profile or the indicators of lipid peroxidation in the placebo group from baseline to the end of the study. The frequency of patients showing increases in lag time was greater in the policosanol group than in the placebo group. Policosanol tended to decrease diene propagation rate, but the mean reduction (11.3%) did not reach statistical significance when compared with placebo. Conclusions: The present study demonstrated that policosanol 5 mg/d not only lowered TC, LDL-C, and atherogenic indices, and increased HDL-C, but also significantly decreased the susceptibility of LDL to copper ion-induced lipid peroxidation in vitro in hypercholesterolemic patients at high coronary risk.