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Antiplatelet therapy, including aspirin, is recommended to lower the vascular risk in patients with intermittent claudication. Policosanol has increased walking distances in these patients, probably because of its antiplatelet effects, but the effect of shorter treatment has not been studied. This double-blind study compared the effects of policosanol 10 mg/d and aspirin 100 mg/d for 10 weeks on walking distances in claudicants. Thirty-nine patients were randomized to policosanol or aspirin. Walking distances on a treadmill were assessed before and after treatment. Policosanol significantly increased the initial and absolute claudication distances, while aspirin changed neither variable. Policosanol, not aspirin, significantly lowered serum low-density lipoprotein-cholesterol and total cholesterol while raising high-density lipoprotein-cholesterol. In conclusion, treatments of policosanol, not aspirin, for 10 weeks significantly increased walking distances, but modestly, in contrast with previous results. Therefore, the duration of treatments at the doses tested was too short for meaningful effects on the treadmill test. [ABSTRACT FROM AUTHOR]

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. The present study was undertaken to compare the effects of policosanol and ticlopidine in patients with moderately severe intermittent claudication (IC). The study had a 4-week baseline step, followed by a 20-week double-blinded, randomized treatment period. Twenty-eight eligible patients were randomized to policosanol 10 mg or ticlopidine 250 mg tablets twice daily (bid). Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees, temperature 25 degrees C) were assessed before and after 20 weeks of treatment. Both groups were similar at baseline. Compared with baseline, policosanol significantly increased (p < 0.01) mean values of initial (ICD) and absolute (ACD) claudication distances from 162.1 to 273.2 m and from 255.8 to 401.0 m, respectively. Ticlopidine also raised significantly (p < 0.01) ICD (166.2 to 266.3 m) and ACD (252.9 to 386.4 m). Comparisons between groups did not show significant differences. Policosanol, but not ticlopidine, significantly (p < 0.05), but modestly, increased the ankle/arm pressure ratio. After 10 weeks, policosanol significantly (p < 0.001) lowered low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) (p < 0.01), and TC/HDL-C and raised (p < 0.05) high-density lipoprotein-cholesterol (HDL-C). At study completion, policosanol lowered (p < 0.001) LDL-C (30.2%), TC (16.9%), and TC/HDL-C (33.9%), increased (p < 0.01) HDL-C (+31.7%), and left triglycerides unchanged. Ticlopidine did not affect the lipid profile variable. Policosanol induced modest, but significant, reductions (p < 0.01) of fibrinogen levels compared with baseline and ticlopidine. Treatments were well tolerated and did not impair safety indicators. Three ticlopidine patients (21.4%) withdrew from the trial, only 1 owing to a serious adverse experience (AE) (unstable angina). Three other ticlopidine patients experienced mild AE (headache, diarrhea, and acidity). It is concluded that policosanol (10 mg bid) can be as effective as ticlopidine (250 mg bid) for improving walking distances of claudicant patients, and it could be advantageous for the global risk of these individuals owing to its cholesterol-lowering effects. This study is, however, just a pilot comparison, so that further studies in larger sample sizes are needed for definitive conclusions of the comparative effects of both drugs on patients with IC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypercholesterolaemia is a risk factor for coronary heart disease (CHD). Clinical studies have shown that lowering elevated serum total cholesterol (TC) levels, and particularly low density lipoprotein-cholesterol (LDL-C) levels, reduces the frequency of coronary morbidity and deaths, whereas high serum levels of high density lipoprotein-cholesterol (HDL-C) protect against CHD. Policosanol is a cholesterol-lowering drug purified from sugar cane wax with a therapeutic dosage range from 5-20 mg/day. Atorvastatin is an HMG-CoA reductase inhibitor which across its dosage range (10-80 mg/day) has shown significantly greater lipid-lowering effects than all previously marketed statins. OBJECTIVE: This study was undertaken to compare the efficacy and tolerability of policosanol with atorvastatin in older patients with type II hypercholesterolaemia. PATIENTS AND METHODS: This randomised, single-blind, parallel-group study was conducted in older patients (60-80 years) with type II hypercholesterolaemia. After 4 weeks on a cholesterol-lowering diet, 75 patients were randomised to policosanol or atorvastatin 10mg tablets taken once daily with the evening meal for 8 weeks. An interim and final check-up were performed at 4 and 8 weeks, respectively, after treatment was initiated. RESULTS: At 4 (p < 0.0001) and 8 (p < 0.00001) weeks, policosanol 10 mg/day significantly lowered serum LDL-C levels by 17.5 and 23.1%, respectively compared with baseline; corresponding values for atorvastatin were 28.4 and 29.8%. At study completion, policosanol significantly (p < 0.0001) reduced serum TC (16.4%), LDL-C/HDL-C ratio (25.5%) and TC/HDL-C ratio (19.3%), as well as (p < 0.001) triglyceride levels (15.4%). Atorvastatin significantly (p < 0.0001) decreased serum TC (22.6%), LDL-C/HDL-C (26.2%) and TC/HDL-C (19.8%) ratios, as well as (p < 0.001) triglyceride levels (15.5%). Atorvastatin was significantly more effective than policosanol in reducing LDL-C and TC, but similar in reducing both atherogenic ratios and triglyceride levels. Policosanol, but not atorvastatin, significantly (p < 0.05) increased serum HDL-C levels by 5.3%. Both treatments were well tolerated. At study completion, atorvastatin mildly, but significantly (p < 0.05) increased creatine phosphokinase (CPK) and creatinine, whereas policosanol significantly reduced AST and glucose (p < 0.01) and CPK (p < 0.05) levels. All individual values, however, remained within normal limits. Three atorvastatin but no policosanol patients withdrew from the study because of adverse events: muscle cramps (1 patient), gastritis (1 patient) and uncontrolled hypertension, abdominal pain and myalgia (1 patient). Overall, no policosanol and seven atorvastatin patients (18.9%) reported a total of nine mild or moderate adverse events during the study (p < 0.01). CONCLUSIONS: This study shows that policosanol (10 mg/day) administered for 8 weeks was less effective than atorvastatin (10 mg/day) in reducing serum LDL-C and TC levels in older patients with type II hypercholesterolaemia. Policosanol, but not atorvastatin, however, significantly increased serum HDL-C levels, whereas both drugs similarly reduced atherogenic ratios and serum triglycerides. Policosanol was better tolerated than atorvastatin as revealed by patient withdrawal analysis and overall frequency of adverse events. Nevertheless, further studies must be conducted in larger sample sizes and using dose-titration methods to achieve target lipid levels in order to reach wider conclusions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of D-003 on the bleeding time (BT) and lipid profile of healthy human volunteers. Methods: This single-blind, randomised, placebo-controlled, parallel-group study was conducted in healthy volunteers. Step 1 investigated the effects of single doses of D-003 5, 25 or 50mg on BT in comparison with placebo. Step 2 investigated the effects of 30 days of D-003 5, 25 or 50 mg/day compared with placebo on lipid profile with an interim assessment at 14 days. BT, lipid profile, physical and haematological safety indicators were measured and adverse events (AEs) recorded. Both steps were followed by a 14- or 30-day washout period Results: Step 1: D-003 25 and 50mg significantly increased mean BT 2 hours after administration compared with baseline, but a significant difference versus placebo occurred only with the 50mg dose. Individual values from participants taking this dose, however, remained within normal limits. This effect was reversible. BT values obtained 2 hours after drug administration showed a moderate dose-dependent relationship. No drug-related changes in safety indicators were found with D-003. Step 2: After 7 days on D-003 50 mg/day, BT was significantly increased compared with baseline and placebo up to the end of the active treatment period. However, all individual values for participants taking this dosage remained within the normal range. This effect was reversible by the end of the washout period. After 30 days, D-003 (5, 25 and 50 mg/day) significantly reduced serum TC (by 13.3 to 17.4%) and LDL-C (by 11.6 to 22.6%) levels, and raised HDL-C levels (by 14.6 to 29.7%), but did not affect triglyceride levels. The significant increase in HDL-C was observed after 14 days on treatment. The effects on the lipid profile were reversible by the end of the 30-day washout period, although after 14 days of washout the effects on HDL-C and LDL-C still remained significant, revealing a certain persistence of effect. Eight participants (four receiving placebo and four receiving D-003 5, 25 or 50 mg/day) reported a total of nine AEs, none of which were drug-related. Of these patients, only two treated with D-003 25 and 50 mg/day discontinued treatment. Conclusions: D-003 in single or repeated doses (50mg) induced significant and reversible increases in BT. In addition, repeated doses (5, 25 and 50 mg/day) significantly and reversibly lowered serum LDL-C and TC levels and significantly raised serum HDL-C levels. These effects were reversible by 30 days after the end of treatment. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to investigate the effects of policosanol administered for 12 months on the lipid profile of older patients with hypertension and type II hypercholesterolaemia and no history of coronary heart disease (CHD) or cerebrovascular disease. Patients and participants: 589 older male and female patients with hypertension and type II hypercholesterolaemia and no history of CHD or cerebrovascular disease were included. Methods: This was a prospective, randomised, double-blind, placebo-controlled study in parallel groups treated with policosanol (5 to 10 mg/day) for 1 year. After 6 weeks on a standard step I cholesterol-lowering diet, 589 patients were randomised to policosanol (5mg) or placebo tablets, to be taken once daily for 12 months. The dosage was doubled to 10 mg/day if total cholesterol values were >6.1 mmol/L after 6 months of therapy. Results: Policosanol significantly (p < 0.00001) lowered serum low-density lipoprotein-cholesterol (LDL-C) [20.5%], total cholesterol (TC) [15.4%], triglycerides (11.9%), LDL-C/high-density lipoprotein-cholesterol (HDL-C) ratio [22.2%] and TC/HDL-C ratio (20.1%), and increased (p < 0.0001) HDL-C (12.7%). The frequency of vascular and all-cause serious adverse events (SAEs) was lower (p < 0.05) in the policosanol recipients (two vascular SAEs, 0.7%; five all-cause SAEs, 1.7%) than in the placebo recipients (six vascular SAEs, 2.0%; 12 all-cause SAEs, 4.1%). Similarly, total adverse events (AEs) were less frequent in the policosanol-treated group (29; 9.8%) compared with the placebo group (52; 17.7%) [p < 0.01]. Three placebo recipients and no policosanol recipients died during the study as a result of myocardial infarction (two patients) and sudden cardiac arrest (one). Policosanol was well tolerated, and no drug-related disturbances in safety indicators were found. Policosanol significantly decreased systolic blood pressure (BP) compared with baseline and placebo, which could be an additional advantage in this population at high coronary risk. Conclusions: Policosanol administered long term is effective in lowering LDL-C and TC as well as increasing HDL-C levels in older patients with hypertension and type II hypercholesterolaemia without a history of CHD or cerebrovascular disease. In addition, policosanol treatment also shows benefits in the occurrence of SAEs of vascular aetiology, on the general AE profile and the reduction of BP in treated patients compared with baseline. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to investigate the effects of policosanol administered for 1 year on the lipid profile and cardiac events of older hypercholesterolaemic patients with coronary heart disease (CHD). Patients: 280 older patients of both sexes with type II hypercholesterolaemia and CHD were included. Methods: Patients were randomised after 6 weeks of a standard step I cholesterol-lowering diet to treatment with policosanol (5mg) or placebo tablets once daily for 1 year. The starting dose was 5 mg/day, which was doubled to 10 mg/day if predefined goals were not reached after 6 months on therapy. Cardiac events were defined as death from cardiovascular causes [fatal myocardial infarction (MI), sudden cardiac death] and nonfatal MI, unstable angina pectoris or coronary surgery. Results: Policosanol significantly (p < 0.00001) lowered serum low-density lipoprotein-cholesterol (LDL-C) [21.3%], total cholesterol (TC) [15.9%], TC to high-density lipoprotein-cholesterol (HDL-C) ratio [22.7%] and LDL-C/HDL-C ratio (26.1%), as well as triglycerides (7.8%, p < 0.001). HDL-C was significantly increased (18.2%, p < 0.001). The frequency of cardiac events was lower (p < 0.001) in policosanol (1 event, 0.7%) than in placebo (11 events, 7.9%) recipients. Likewise, the frequency of all vascular serious adverse events (four events, 2.9%) and all-cause hospitalisations in the policosanol group (five events, 3.6%) was lower (p < 0.001) than in the placebo group (15 and 20 events, 10.7 and 14.3%, respectively). No patient died during the study. Policosanol was well tolerated. Conclusions: Long-term policosanol is effective in lowering LDL-C and TC and in increasing HDL-C levels in older patients with CHD, and also showed benefits in the occurrence of cardiac events and overall frequency of serious adverse events of vascular aetiology. [ABSTRACT FROM AUTHOR]

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 < .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. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis begins in childhood and is influenced by risk factors for coronary heart disease (CHD), of which hypercholesterolemia is crucial. The rationale for treating hypercholesterolemia in childhood is to limit atherosclerosis development, for which adherence to a cholesterol-lowering diet is the first-choice therapy. Nevertheless, pharmacological intervention with bile acid-binding resins may be prescribed for patients older than 10 years, mainly those with family history of CHD, multiple risk factors, and/or severe hypercholesterolemia. Resins are effective and tolerable in this population, but their clinical use has been limited because of poor compliance due to unpalatability; other effective cholesterol-lowering drugs have not been recommended in this population because of the potential impact of drug-related adverse effects such as increases in transaminases, myopathies, and gastrointestinal disturbances. Thus, the need for safer, easy-to-take, and effective cholesterol-lowering agents for this population continues. Policosanol is a mixture of higher primary aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects proven in patients with type II hypercholesterolemia and dyslipidemia due to type 2 diabetes mellitus. Policosanol shows good safety and tolerability profiles, with no evidence of drug-related adverse events (AEs) to date. This background supports the idea that policosanol could be a good candidate for treating hypercholesterolemia in children and adolescents, but it requires clinical demonstration.Objective: This 12-week study was undertaken to investigate the cholesterol-lowering effects and tolerability of policosanol in hypercholesterolemic patients aged 11 to 19 years.Methods: In this randomized, double-blind, placebo-controlled study, after 4 weeks of dietary stabilization, adolescents with type II hypercholesterolemia were randomly assigned (1:1 ratio) to receive placebo or policosanol 5-mg tablets once daily for 12 weeks. Physical examinations were performed, and lipid profiles and blood samples were obtained at baseline and after 6 and 12 weeks of therapy. The treatment was considered effective if mean reductions of low-density lipoprotein cholesterol (LDL-C) were>15%. In addition, the percentages of patients reaching final values of LDL-C <3.4 mmol/L and optimal values of <2.8 mmol/L were also evaluated. The doses were doubled if LDL-C values were +/- 3.4 mmol/L after 6 weeks of therapy. The incidence of AEs and compliance with study medications were also evaluated after 6 and 12 weeks of treatment.Results: Fifty-five patients were enrolled in the study (28 policosanol, 27 placebo). Twenty-three patients (17 placebo, 6 policosanol) required dose titration at 6 weeks. After 12 weeks of therapy, policosanol significantly decreased LDL-C with respect to baseline and placebo (both P < 0.001), showing a mean reduction of 32.6%. Total cholesterol (TC) and TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were reduced by 21.9%, 27.8%, and 37.2%, respectively, in the policosanol group (P < 0.001, compared with baseline and placebo). HDL-C rose 10.1% (P < 0.001), compared with baseline and placebo. Triglycerides were unaffected by policosanol. LDL-C, TC, and both atherogenic ratios were reduced significantly in the policosanol group (P < 0.001), and significant increases in HDL-C values were observed at the 6-week interim checkup (P < 0.001 vs baseline, P < 0.01 vs placebo). Twenty-five (89.3%) of 28 patients in the policosanol group showed LDL-C reductions>15% compared with 2 (7.4%) of 27 patients in the placebo group (P < 0.001). In addition, 26 (92.8%) of 28 policosanol patients reached LDL-C values < 3.4 mmol/L compared with 4 (14.8%) of 27 patients in the placebo group (P < 0.001). Likewise, the response rate for achievement of optimal values (LDL-C < 2.8 mmol/L) was also larger in the policosanol group (20/28; 71.4%) than in the placebo group (0/27; 0.0%) (P < 0.001). Policosanol was well tolerated, with no drug-related effects found on physical examination. Blood biochemistry determinations revealed significantly lower alanine aminotransferase levels in the policosanol group after 6 weeks of therapy compared with placebo (P < 0.05), as well as significant reductions in aspartate aminotransferase levels at 6 weeks (P < 0.01) and 12 weeks (P < 0.05) compared with baseline. No patients withdrew from the study, and only 3 patients (2 placebo, 1 policosanol) experienced mild AEs during the study; the placebo patients reported abdominal pain and constipation (1 each), and the policosanol patient reported polyphagia.Conclusions: Policosanol 5 mg/d appears to be well tolerated and effective as short-term treatment of hypercholesterolemia in adolescents. [ABSTRACT FROM AUTHOR]

Both hypercholesterolemia (HC) and obesity are coronary risk factors. Clinical studies have shown the benefits of lowering elevated plasma levels of low-density lipoprotein-cholesterol (LDL-C) on clinical end-points. Policosanol is a cholesterol-lowering drug purified from sugar cane wax with a therapeutic range from 5 to 20 mg/day. This randomised, double-blinded, placebo-controlled study was undertaken to investigate the long-term efficacy and safety of policosanol in obese patients (BMI = 30) with Type II hypercholesterolemia. After 5 weeks on step one cholesterol-lowering diet, 129 patients were randomised to policosanol 5 mg or placebo tablets taken once daily with the evening meal for 3 years. Lipid profile variables, safety indicators, adverse events (AE) and compliance with diet counselling and study medications were assessed. Study patiens showed a high frequency of other coronary risk factors, hypertension being the most common. Both groups were well matched at randomisation. After one year on treatment, policosanol significantly (p < 0.01 vs placebo) lowered serum LDL-C, the primary efficacy variable (24.3 %) and total cholesterol (TC) (15.8 %), whereas increased high-density lipoprotein-cholesterol (HDL-C) (21.9 %). Changes of lipid variables in placebo were not significant. Treatment effects were persistent, even slightly enhanced, during the trial. At study completion, policosanol had lowered (p < 0.00001) LDL-C (31.8 %) and TC (20.1 %), while markedly raised (p <0.00001) HDL-C (24.6 %). Thirty patients (18 placebo, 12 policosanol) discontinued the study: 15 (11 placebo, 4 policosanol) due to AE and 12 (9 placebo, 3 policosanol) due to serious adverse events (SAE), most vascular. Policosanol was safe and well tolerated, not impairing significantly any safety indicator. Average body weight was slightly reduced over the study, indicating a general acceptable compliance with dietary recommendations, but policosanol did not show any drug effect on body weight. Overall, 28 placebo and 26 policosanol patients reported some mild or moderate AE during the study. It is concluded that policosanol was effective for lowering cholesterol in obese patients with type II hypercholesterolemia, being also safe and well tolerated. [ABSTRACT FROM AUTHOR]

Diabetes and hypercholesterolemia are major coronary risk factors. Coronary risk of diabetics is also greater than non-diabetics. The main goal of dyslipidemia control in diabetics is to lower elevated low-density lipoproteincholesterol (LDL-C) levels. Policosanol is a cholesterol-lowering drug purified from sugar cane wax, which significantly reduces LDL-C levels and inhibits platelet aggregation. Previous short-term studies have shown the efficacy and tolerability of policosanol at 10 mg/day on patients with Type 2 diabetes, but no previous study on the effects of long-term treatment or lower doses has been reported. This study was undertaken to investigate the longterm efficacy, safety and tolerability of policosanol on patients with Type 2 diabetes. After 5 weeks on a step one cholesterol lowering diet, 239 patients with Type 2 diabetes were randomized to policosanol 5 mg/day or placebo for 2 years. Analysis was by Intention-to-treat. Baseline characteristics were well matched in both groups. After one year, policosanol reduced significantly (p < 0.0001 versus baseline and placebo) low-density lipoprotein-cholesterol (LDLC) (21.1 %), total cholesterol (TC) (17.5 %) and triglycerides (TG) (16.0 %), whereas increased (p < 0.01 versus baseline and placebo) high-density lipoprotein-cholesterol (HDL-C) levels (10.7 %). Treatment effects on LDL-C, HDL-C and TC persisted, even moderately enhanced, during the study, the effect on TG being persistent too Thus, at study completion, policosanol lowered (p < 0.0001 vs baseline and placebo) LDL-C (29.5 %), TC (21.9 %), TG (16.9 %) and raised (p < 0.0001 vs baseline and placebo) HDL-C (12.4 %). No significant changes on lipid profile variables of placebo group occurred during the study. Of 239 randomized patients, 63 (26.4 %) discontinued the study, 43/120 placebo (35.8 %) and 20/119 policosanol patients (16.8 %). Of them, 35 patients (28 placebo, 7 policosanol) withdrew from the study due to some AE. The frequency of serious adverse events (SAE), most vascular, in policosanol patients (6/119, 5.0 %) was lower than in respective placebo (26/120, 43.3 %). Five patients, all placebo, died during the study, four of them due to myocardial infarction. No drug-related impairment of safety indicators, particularly on glycemic control, was observed. Nevertheless, a reduction of systolic and diastolic blood pressure was observed in policosanol patients compared with placebo. The overall frequency of policosanol patients reporting mild and/or moderate was similar than in placebo. It is concluded that policosanol was long-term effective, safe and well tolerated on patients with dyslipidemia due to Type 2 diabetes. [ABSTRACT FROM AUTHOR]