Medical Surgical Research Center, Havana City, Cuba.
Clin Drug Investig. 2003;23(10):639-50. doi: 10.2165/00044011-200323100-00003.
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.
To compare the effects on lipid profile and platelet aggregation of policosanol and atorvastatin in patients with dyslipidaemia due to type 2 diabetes.
This randomised, single-blind, parallel-group study was conducted in patients with type 2 diabetes (fasting glucose </=7 mmol/L and glycosylated haemoglobin [HbA(1c)] <8.5%) and high LDL-C levels (>/=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.
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.
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.
糖尿病和高胆固醇血症增加了冠心病的风险，其中 2 型糖尿病是最常见的糖尿病类型，常伴有血脂异常。非糖尿病和糖尿病患者血脂异常控制的主要目标是降低升高的低密度脂蛋白胆固醇（LDL-C）水平。聚乙二醇化多不饱和脂肪酸是一种从甘蔗蜡中提取的降胆固醇药物，治疗范围为 5-20mg/天，可显著降低 LDL-C 水平。阿托伐他汀是一种 HMG-CoA 还原酶抑制剂，在其剂量范围内（10-80mg/天），与所有以前上市的他汀类药物相比，降脂效果显著更大。
比较聚乙二醇化多不饱和脂肪酸和阿托伐他汀对 2 型糖尿病血脂异常患者的血脂谱和血小板聚集的影响。
这是一项随机、单盲、平行组研究，纳入了 LDL-C 水平升高（≥3.0mmol/L）且空腹血糖≤7mmol/L 和糖化血红蛋白（HbA（1c））<8.5%的 2 型糖尿病患者。在进行 6 周的降胆固醇饮食后，将 40 名患者随机分为聚乙二醇化多不饱和脂肪酸或阿托伐他汀 10mg 片剂组，每日一次，随晚餐服用，持续 8 周。评估血脂谱、血小板聚集试验、安全性指标和不良事件。
治疗 8 周后，聚乙二醇化多不饱和脂肪酸可显著降低 LDL-C 25.7%（p<0.0001 与基线相比）和总胆固醇（TC）18.2%（p<0.001 与基线相比）。相比之下，阿托伐他汀 10mg/天可降低 LDL-C 41.9%和 TC 31.5%（p<0.0001 与基线相比）。阿托伐他汀在降低 LDL-C 和 TC 方面比聚乙二醇化多不饱和脂肪酸更有效（p<0.001）。聚乙二醇化多不饱和脂肪酸还可显著降低 TC/高密度脂蛋白胆固醇（HDL-C）比值（25.2%；p<0.0001）和甘油三酯（15.6%；p<0.001），而阿托伐他汀可降低 TC/HDL-C 30.5%（p<0.0001）和甘油三酯 13.9%（p<0.001）；两组之间这些变量的降低情况相似。聚乙二醇化多不饱和脂肪酸，而不是阿托伐他汀，可显著增加 HDL-C（11.1%；p<0.01），其效果与阿托伐他汀显著不同（p<0.0001）。此外，聚乙二醇化多不饱和脂肪酸，而不是阿托伐他汀，可显著抑制花生四烯酸 0.75 和 1.5mmol/L（分别为 39.0%和 33.3%）和胶原 0.25 和 0.5μg/ml（分别为 15.7%和 28.5%）诱导的血小板聚集（p<0.001）；这些抑制作用与阿托伐他汀有显著差异（p<0.05）。两种药物均不能显著改变由二磷酸腺苷（ADP）诱导的血小板聚集。两种治疗方法均耐受性良好，血糖控制不受影响。两种药物均未损害肝功能安全指标或血糖控制指标（空腹血糖和 HbA（1c））。阿托伐他汀可显著升高丙氨酸氨基转移酶（ALT）[p<0.05]和肌酸磷酸激酶（CPK）[p<0.01]水平，而聚乙二醇化多不饱和脂肪酸则不能显著改变任何安全指标。只有三名阿托伐他汀患者的 ALT 和 CPK 值略有升高（<正常上限的 3 倍）。没有患者退出研究。四名患者报告了不良反应：两名聚乙二醇化多不饱和脂肪酸（失眠和瘙痒）和两名阿托伐他汀（肌痛和血压升高）患者。
聚乙二醇化多不饱和脂肪酸（10mg/天）治疗 8 周，在降低 2 型糖尿病血脂异常患者的 LDL-C 和 TC 方面的效果不如类似剂量的阿托伐他汀，但在升高 HDL-C 方面的效果更好。两种药物均能显著降低 TC/HDL-C 比值和甘油三酯。聚乙二醇化多不饱和脂肪酸在抑制血小板聚集方面具有额外的优势。然而，需要进行更长时间的研究，并采用剂量滴定方案来实现 LDL-C 目标，以便对这两种药物在该人群亚组中的各自作用得出更广泛的结论。
