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.

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.

CONCLUSIONS

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.