Comparison of the efficacy and tolerability of policosanol with atorvastatin in elderly patients with type II hypercholesterolaemia.

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.

Comparison of the effects of policosanol and atorvastatin on lipid profile and platelet aggregation in patients with dyslipidaemia and type 2 diabetes mellitus.

BACKGROUND: Diabetes mellitus and hypercholesterolaemia increase the risk for coronary heart disease, with type 2 diabetes mellitus being the most prevalent form of diabetes, frequently accompanied by dyslipidaemia. The main goal of dyslipidaemia control in nondiabetic and diabetic patients is to lower elevated low-density lipoprotein-cholesterol (LDL-C) levels. Policosanol is a cholesterol-lowering drug, purified from sugarcane wax, with a therapeutic range of 5-20 mg/day, which significantly reduces LDL-C levels. Atorvastatin is an HMG-CoA reductase inhibitor that, across its dose range (10-80 mg/day), has shown significantly greater lipid-lowering effects than all previously marketed statins. OBJECTIVE: To compare the effects on lipid profile and platelet aggregation of policosanol and atorvastatin in patients with dyslipidaemia due to type 2 diabetes. PATIENTS AND METHODS: This randomised, single-blind, parallel-group study was conducted in patients with type 2 diabetes (fasting glucose /=3.0 mmol/L). After 6 weeks on a cholesterol-lowering diet, 40 patients were randomised to policosanol or atorvastatin 10mg tablets taken once daily with the evening meal for 8 weeks. Assessments of lipid profile, platelet aggregation tests, safety indicators and adverse events were performed. RESULTS: After 8 weeks of therapy, policosanol significantly lowered LDL-C by 25.7% (p < 0.0001 versus baseline) and total cholesterol (TC) by 18.2% (p < 0.001 versus baseline). In turn, atorvastatin 10 mg/day decreased LDL-C by 41.9% and TC by 31.5% (p < 0.0001 versus baseline). Atorvastatin was more effective than policosanol in reducing LDL-C and TC (p < 0.001). Policosanol also significantly reduced the TC/high-density lipoprotein-cholesterol (HDL-C) ratio (25.2%; p < 0.0001) and triglycerides (15.6%; p < 0.001), while atorvastatin lowered TC/HDL-C by 30.5% (p < 0.0001) and triglycerides by 13.9% (p < 0.001); the reductions on these variables were similar in the two groups. Policosanol, but not atorvastatin, significantly increased HDL-C (11.1%; p < 0.01), the effect being significantly different from that of atorvastatin (p < 0.0001). Also, policosanol, but not atorvastatin, significantly inhibited platelet aggregation induced by arachidonic acid 0.75 and 1.5 mmol/L (39.0% and 33.3%, respectively) and by collagen 0.25 and 0.5 mug/mL (15.7% and 28.5%, respectively) [p < 0.001]; these inhibitions were significantly different (p < 0.05) from the changes that occurred with atorvastatin. Neither drug significantly changed platelet aggregation elicited by adenosine diphosphate (ADP). Both treatments were well tolerated, with glycaemic control being unaffected. Neither drug impaired physical safety indicators or glucose control indicators (fasting glucose and HbA(1c)). Atorvastatin significantly increased levels of alanine aminotransferase (ALT) [p < 0.05] and creatine phosphokinase (CPK) [p < 0.01], while policosanol did not significantly change any safety indicator. Only three atorva-statin recipients showed individual values of ALT and CPK that were moderately enhanced (<3 times above the normal upper limit). No patients withdrew from the study. Four patients reported adverse events: two policosanol (insomnia and pruritus) and two atorvastatin (myalgia and raised arterial blood pressure) recipients. CONCLUSION: Policosanol (10 mg/day) for 8 weeks was less effective than similar doses of atorvastatin in reducing LDL-C and TC in patients with dyslipidaemia due to type 2 diabetes, but more effective in increasing HDL-C. Both drugs similarly reduced the TC/HDL-C ratio and triglycerides. Policosanol showed additional advantages regarding inhibition of platelet aggregation. Nevertheless, further studies of longer duration and using dose-titration schemes to achieve LDL-C goals are needed for wider conclusions about the respective effects of these two drugs in such a population subset.

Effects of D-003 on the Lipid Profile of Patients with Type II Hypercholesterolaemia : A Phase II Clinical Study.

BACKGROUND: D-003 is a cholesterol-lowering agent that is isolated and purified from sugarcane wax and has concomitant antiplatelet effects. OBJECTIVE: To evaluate lipid profile responses to different doses of D-003 in patients with type II hypercholesterolaemia. STUDY DESIGN: An 8-week, double-blind, placebo-controlled, parallel-group clinical study. METHODS: After concluding a 5-week diet-only baseline period, 55 patients were randomly allocated to receive either placebo or D-003 at 5, 10, 20 or 40mg once daily with their evening meal for 8 weeks. An interim check-up was performed at week 4. The primary efficacy variable was the reduction of serum low-density lipoprotein-cholesterol (LDL-C) from baseline compared with placebo. Drug safety and tolerability were assessed on the basis of changes in physical, haematological and blood biochemical indicators and on questioning about adverse experiences (AEs). RESULTS: After 8 weeks of therapy, D-003 significantly lowered (p < 0.0001 vs baseline and placebo) serum LDL-C in a dose-related manner, with reductions of 20.5-26.1% from the lowest to the highest dose investigated. At study completion, 43 of 44 (97.7%) randomised patients treated with D-003 reached LDL-C reductions >15% compared with baseline, while 30 of 44 patients (68.2%) reached LDL-C targets according to their individual global coronary risk status. Decreases in total cholesterol (TC) and the ratios of TC/high-density lipoprotein-cholesterol (HDL-C) and LDL-C/HDL-C were also significant (p < 0.0001) and dose related. Changes in LDL-C, TC and both ratios were significant from the interim check-up. D-003 significantly increased HDL-C values (11.7-16.7%), but the increase was not dose related. No significant changes in lipid profile variables were observed with placebo. D-003 was well tolerated. The treatment did not affect any physical, haematological or blood safety indicators. All included patients completed the study. Four patients reported mild AEs during the study: headache (one patient treated with placebo and one treated with D-003 20 mg/day), insomnia (one patient treated with D-003 5 mg/day) and polyuria (one patient treated with D-003 40 mg/day). CONCLUSIONS: D-003 was effective in dose dependently reducing LDL-C in patients with type II hypercholesterolaemia, as documented by average percentage reductions and the percentage of patients achieving decreases >15% from baseline and LDL-C goals. The treatment was well tolerated by patients and did not affect any safety indicator. Further studies corroborating these results and exploring the effect of lower doses of D-003 and a longer treatment duration must be carried out, however, before definitive conclusions can be reached. These results encourage continuing clinical investigation on this drug.

Effects of policosanol on borderline to mildly elevated serum total cholesterol levels: a prospective, double-blind, placebo-controlled, parallel-group, comparative study.

BACKGROUND: Hypercholesterolemia is a major risk factor for coronary heart disease. Clinical studies have shown that lowering elevated serum cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is beneficial for patients with borderline to mildly elevated serum total cholesterol (TC) levels (5.0-6.0 mmol/L). Policosanol is a cholesterol-lowering drug made from purified sugar cane wax. The therapeutic range of policosanol is 5 to 20 mg/d. OBJECTIVE: This study investigated the efficacy and tolerability of policosanol 5 mg/d in patients with borderline to mildly elevated serum TC levels. METHODS: This 14-week, single-center, prospective, double-blind, placebo-controlled, parallel-group, comparative study was conducted in men and women aged 25 to 75 years with a serum TC level ≥4.8 to <6.0 mmol/L. After a 6-week run-in period in which patients were placed on therapeutic lifestyle changes, in particular a cholesterol-lowering diet, patients were randomly assigned to receive policosanol 5-mg tablets or placebo tablets once daily with the evening meal for 8 weeks, and the diet was continued throughout the study. Lipid profile variables, safety indicators, adverse events (AEs), and compliance with study medications were assessed. RESULTS: One hundred patients (71 women, 29 men; mean [SD] age, 52 [10] years) entered the study after the dietary run-in period. After 8 weeks of treatment, the mean (SD) serum LDL-C level decreased significantly in the policosanol group (P<0.001 vs baseline and placebo) from 3.57 (0.30) mmol/L to 2.86 (0.41) mmol/L (change, -19.9%). Significantly more patients in the policosanol group (42 patients [84%]) achieved a ≥15% decrease in serum LDL-C than in the placebo group (2 patients [4%]) (P<0.001). Also in the policosanol group, the mean (SD) serum TC level decreased significantly, from 5.20 (0.22) mmol/L to 4.56 (0.44) mmol/L (P<0.001 vs baseline and placebo) (change, -12.3%); the mean (SD) triglyceride (TG) level decreased significantly, from 1.59 (0.57) mmol/L to 1.48 (0.57) mmol/L (P<0.01 vs baseline; P<0.05 vs placebo) (change, -6.9%); and the mean (SD) high-density lipoprotein cholesterol (HDL-C) level increased significantly from 1.05 (0.18) mmol/L to 1.16 (0.21) mmol/L (P<0.001 vs baseline and placebo) (change, +10.5%). The percentage changes were significantly different between the policosanol and placebo groups for serum LDL-C, TC, and HDL-C levels (P<0.001, P<0.001, and P<0.05, respectively), but not for TG. In the placebo group, changes in lipid profile variables from baseline were not significant. Policosanol did not significantly impair any safety indicator and was well tolerated. Three patients (3%) (1 patient [2%] in the policosanol group; 2 patients [4%] in the placebo group) withdrew from the trial, none because of AEs. Two patients (1 patient [2%] each in the policosanol and placebo groups) withdrew from the study because of an unwillingness to return for follow-up; 1 patient (2%) in the placebo group had a change of address and could not be followed up. Overall, 4 patients (4%) (1 patient [2%] in the policosanol group; 3 [6%], placebo) reported AEs; all were mild. Of the patients who received placebo and reported AEs, all 3 (6%) experienced heartburn, and 1 (2%) also experienced dry skin, while the policosanol-treated patient (2%) who reported an AE experienced headache. CONCLUSIONS: In this study of patients with borderline to mildly elevated serum TC levels, based on the criterion that ≥70% of policosanol-treated patients reached the LDL-C goal of a decrease ≥15% from baseline whenever this proportion was different with respect to placebo, 8 weeks of treatment with policosanol 5 mg/d was effective. The decreased LDL-C, TC, and TG levels, increased HDL-C level, and good tolerability found with this treatment support its use in such patients.