Efficacy and tolerability of policosanol in hypercholesterolemic postmenopausal women.
This randomized, double-blind, multicenter placebo-controlled study was conducted to investigate the efficacy and tolerability of policosanol, a cholesterol-lowering drug purified from sugar cane wax, in women who had experienced menopause and showed elevated serum total cholesterol and low density lipoprotein (LDL)-cholesterol levels despite a 6-week standard lipid-lowering diet. Thus, 56 eligible patients were randomized to receive placebo or policosanol 5 mg/day for 8 weeks and the dose was doubled to 10 mg/day during the next 8 weeks. Policosanol (5 and 10 mg/day) significantly decreased LDL-cholesterol (17.3% and 26.7%, respectively), total cholesterol (12.9% and 19.5%) as well as the ratios of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (17.2% and 26.5%) and total cholesterol to HDL-cholesterol (16.3% and 21.0%) compared with baseline and placebo. HDL-cholesterol levels were significantly raised by 7.4% at study completion. No significant changes occurred in the lipid profile of the placebo group. The drug was safe and well tolerated. No drug- related adverse effects were observed. None of the patients administered policosanol but three of those administered placebo withdrew from the trial because of adverse effects: one due to a serious hypertensive status, one because of an allergic reaction (pruritus plus skin rash) and one due to gastrointestinal disturbances (nauseas plus vomiting). Eleven placebo patients reported 24 adverse effects compared with six policosanol patients who reported seven adverse effects (p < 0.05). In addition, five placebo (17.9%) and 13 policosanol patients (46.4%) (p < 0.05) reported improvements in habitual symptoms and health perception during the study. In conclusion, policosanol was effective and well tolerated in hypercholesterolemic postmenopausal women, showing additional benefits in the health perception of the study patients.
Int J Clin Pharmacol Res 2001;21(1):31-41
Effects of policosanol in older patients with type II hypercholesterolemia and high coronary risk.
BACKGROUND: The present study was undertaken to investigate the effects of policosanol in older patients with type II hypercholesterolemia and more than one concomitant atherosclerotic risk factor. METHODS: After 6 weeks on a lipid-lowering diet, 179 patients randomly received a placebo or policosanol at doses of 5 followed by 10 mg per day for successive 12-week periods of each dose. Policosanol (5 and 10 mg/d) significantly (p < .001) reduced low-density lipoprotein cholesterol (LDL-C; 16.9% and 24.4%, respectively) and total cholesterol (TC; 12.8% and 16.2%, respectively), while significantly (p é .01) increasing (p < .001) high-density lipoprotein cholesterol (HDL-C) by 14.6% and 29.1%, respectively. RESULTS: Policosanol significantly decreased (p < .01) the ratios of LDL-C to HDL-C (29.1%) and TC to HDL-C (28%) at study completion, although triglycerides remained unchanged. Policosanol, but not the placebo, significantly improved (p .01) cardiovascular capacity, which was assessed using the Specific Activity Scale. No serious adverse experiences occurred in policosanol patients (p < .01), compared with seven adverse experiences (7.9%) reported by placebo patients. CONCLUSIONS: This study shows that policosanol is effective, safe, and well tolerated in older hypercholesterolemic patients.
J Gerontol A Biol Sci Med Sci 2001 Mar;56(3):M186-92
A long-term study of policosanol in the treatment of intermittent claudication.
Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication. The study consisted of a 6-week single-blind, placebo-controlled run in phase, followed by a 2-year double-blind, randomized treatment step. Fifty-six patients who met study entry criteria were randomized to receive placebo or policosanol 10 mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope 10 degrees, temperature 25 degrees C) were assessed before and after 6, 12, 18, and 24 months of treatment. Both groups were similar at randomization. After 6 months of therapy, policosanol significantly increased (p < 0.01) the initial claudication distance from 125.9 +/- 8.7 m to 201.1 +/- 24.8 m and the absolute claudication distance from 219.5 +/- 14.1 m to 380.7 +/- 50.2 m. Both variables remained unchanged in the placebo group (p < 0.01). These effects did not wear off but improved after long-term therapy, so that final values were 333.5 +/- 28.6 m (initial claudication distance) and 648.9 +/- 54.1 m (absolute claudication distance); both significantly greater (p < 0.0001) than those obtained in the placebo group, which showed values of 137.9 +/- 21.8 m (initial claudication distance) and 237.7 +/- 28.1 m (absolute claudication distance), respectively. At study completion, 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50% (p < 0.001). Policosanol, but not placebo, significantly increased the ankle/arm pressure index. In addition, from month 6 up to study completion, the frequency of patients reporting improvement of lower limb symptoms was greater in the policosanol group than in the placebo group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4 policosanol) from the study. Eight patients in the placebo group experienced a total of 10 serious adverse events, 8 of which were vascular events, compared with none in the policosanol group (p < 0.01). In addition, 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study. The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication.
Angiology 2001 Feb;52(2):115-25
Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors.
INTRODUCTION: This study was undertaken to evaluate the efficacy, safety, and tolerability of policosanol, a new cholesterol-lowering drug, in patients with type II hypercholesterolemia and additional coronary risk factors. PATIENTS AND METHODS: After 5 weeks of a standard step-1 lipid-lowering diet, 437 patients were randomized to receive, under double-blind conditions, 5 mg policosanol or placebo once a day with the evening meal for 12 weeks and 10 mg policosanol or placebo for the next 12 weeks. RESULTS: Both groups were similar at randomization. Policosanol (5 and 10 mg/day) significantly reduced (P Z .001) serum low-density lipoprotein cholesterol (18.2% and 25.6%, respectively) and cholesterol (13.0% and 17.4%), and it significantly raised (P < .01) high-density lipoprotein cholesterol (15.5% and 28.4%). Triglycerides remained unchanged after the first 12 weeks and lowered significantly (5.2%; P < .01) at study completion. Policosanol was safe and well tolerated, and no drug-related disturbances were observed. Two male patients who received placebo died during the study—one because of a myocardial infarction and the other because of a cardiac arrest that occurred during a surgical intervention. There were 11 serious adverse events (5.1%) in 10 patients who received placebo (4.6%), 7 of which were vascular, compared with no serious adverse events reported in patients receiving policosanol (P < .01). CONCLUSIONS: Subjects in the group treated with policosanol did not have serious adverse events during the 24-week study. This study shows that policosanol is effective, safe, and well tolerated in patients with hypercholesterolemia and concomitant coronary risk factors.
Clin Pharmacol Ther 1999 Apr;65(4):439-47
Effect of policosanol on lipofundin-induced atherosclerotic lesions in rats.
Policosanol is a mixture of higher aliphatic alcohols isolated from sugar cane wax, showing cholesterol-lowering effects and preventing the development of lipofundin-induced lesions in New Zealand rabbits. This study was conducted to determine whether policosanol orally administered to rats also protects against the development of lipofundin-induced atherosclerotic lesions. Fifty four male Wistar rats were randomly distributed amongst a negative control group, a positive control group intravenously injected with lipofundin for eight days, and four experimental groups also injected with lipofundin, but orally receiving policosanol at 0.5, 2.5, 5 and 25 mg kg-1, respectively. Policosanol treatment was orally administered once-a-day for eight days, while control groups similarly received equivalent amounts of vehicle. A significant reduction of the atherosclerotic lesions in the treated animals was observed. It is concluded that policosanol has a protective effect on lipofundin-induced aortic lesions in Wistar rats.
J Pharm Pharmacol 1995 Apr;47(4):289-91
Protective effect of policosanol on atherosclerotic lesions in rabbits with exogenous hypercholesterolemia.
Policosanol is a mixture of higher aliphatic alcohols purified from sugar cane wax, with cholesterol-lowering effects demonstrable in experimental models and in patients with type II hypercholesterolemia. The protective effects of policosanol on atherosclerotic lesions experimentally induced by lipofundin in rabbits and rats and spontaneously developed in stumptail monkeys have been described. The present study was conducted to determine whether policosanol administered orally to rabbits with exogenous hypercholesterolemia also protects against the development of atherosclerotic lesions. Male New Zealand rabbits weighing 1.5 to 2 kg were randomly divided into three experimental groups which received 25 or 200 mg/kg policosanol (N = 7) orally for 60 days with acacia gum as vehicle or acacia gum alone (control group, N = 9). All animals received a cholesterol-rich diet (0.5%) during the entire period. Control animals developed marked hypercholesterolemia, macroscopic lesions and arterial intimal thickening. Intima thickness was significantly less (32.5 +/- 7 and 25.4 +/- 4 microm) in hypercholesterolemic rabbits treated with policosanol than in controls (57.6 +/- 9 microm). In most policosanol-treated animals, atherosclerotic lesions were not present, and in others, thickness of fatty streaks had less foam cell layers than in controls. We conclude that policosanol has a protective effect on the atherosclerotic lesions occurring in this experimental model.
Braz J Med Biol Res 2000 Jul;33(7):835-40
Oral administration of policosanol inhibits in vitro copper ion-induced rat lipoprotein peroxidation.
Policosanol, a new cholesterol-lowering agent, is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) wax, which prevents the onset of espontaneously and experimentally induced atherosclerotic lesions in experimental models. Because the oxidation of low-density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis, we investigate the effect of policosanol on copper oxidative susceptibility of rat lipoprotein fractions (VLDL + LDL). Rats fed normal diet were treated with policosanol (250-500 mg/kg/day) for up to 4 weeks. EDTA-free lipoprotein particles were oxidized in a cell-free system by the addition of copper ions, and conjugated dienes generation was monitored by changes of optical density at 234 nm. Thiobarbituric acid-reactive substances (TBARS) content and lysine-amino group reactivity were investigated. After administration, there was no change in cholesterol, triglycerides, and phospholipid content of lipoprotein fractions; however, policosanol significantly prolongs the lag time and reduces the propagation rate of diene generation. Also, policosanol reduces TBARS content and increases lysine reactivity in lipoprotein fractions treated with Cu2+. In conclusion, policosanol, in addition to its cholesterol-lowering effect, has other properties that enables it to reduce the potential of lipoprotein to undergo lipid peroxidation. Such effect can be considered of promissory value in the management of atherosclerosis.
Physiol Behav 1999 Aug 1;67(1):1-7
Effect of policosanol on foam-cell formation in carrageenan-induced granulomas in rats.
Policosanol is a new cholesterol-lowering drug isolated and purified from sugar-cane wax, which prevents the development of lipofundin-induced lesions and foam-cell formation in New Zealand rabbits and Wistar rats. This study was conducted to examine the effects of policosanol on foam-cell formation in carrageenan-induced granulomas in rats. Eighteen Wistar rats were randomly distributed in three experimental groups which received orally for 20 days Tween 20 H2O as vehicle (control group) or policosanol at 2.5 or 25 mg kg-1. At the 11th day, lipofundin was injected intraperitoneally for 8 days to induce formation of foam cells in the granuloma. At day 13, carrageenan was injected subcutaneously for granuloma induction and seven days later animals were killed. A significant reduction of the foam-cell formation in granulomas of policosanol-treated rats was observed. It is concluded that policosanol prevents the development of foam cells in carrageenan-induced granulomas (extravascular medium) in rats.
J Pharm Pharmacol 1996 Mar;48(3):306-9