Effects of addition of policosanol to omega-3 fatty acid therapy on the lipid profile of patients with type II hypercholesterolaemia

BACKGROUND: Policosanol is a mixture of higher aliphatic primary alcohols purified from sugar-cane wax. The mixture has cholesterol-lowering efficacy, its specific effects being to reduce serum total (TC) and low-density lipoprotein cholesterol (LDL-C), and to increase high-density lipoprotein cholesterol (HDL-C). The effects of policosanol on triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol. OBJECTIVE: To investigate whether combined therapy with omega-3 FA + policosanol offers benefits compared with omega-3 FA + placebo with respect to the lipid profile of patients with type II hypercholesterolaemia. METHODS: This randomised, double-blind study was conducted in 90 patients with type II hypercholesterolaemia. After 5 weeks on a cholesterol-lowering diet, patients were randomised to omega-3 FA + placebo, omega-3 FA + policosanol 5 mg/day or omega-3 FA + policosanol 10 mg/day for 8 weeks. Omega-3 FA was supplied as 1g capsules (two per day); placebo and policosanol were provided in tablet form. Physical signs and laboratory markers were assessed at baseline and after 4 and 8 weeks on therapy. Drug compliance and adverse experiences (AEs) were assessed at weeks 4 and 8. The primary efficacy variable was LDL-C reduction; other lipid profile markers were secondary variables. RESULTS: After 8 weeks, omega-3 FA + policosanol 5 and 10 mg/day, but not omega-3 FA + placebo, significantly reduced LDL-C by 21.1% and 24.4%, respectively (both p < 0.0001). Omega-3 FA + policosanol 5 mg/day also significantly lowered TC (12.7%; p < 0.01) and TG (13.6%; p < 0.05), and significantly increased HDL-C (+14.4%; p < 0.001). Omega-3 FA + policosanol 10 mg/day significantly decreased TC (15.3%; p < 0.001) and TG (14.7%; p < 0.01), and significantly increased HDL-C (+15.5%; p < 0.0001). Omega-3 FA + placebo significantly reduced TG (14.2%; p < 0.05) but had no significant effect on other lipid profile variables. The proportion of randomised patients in the omega-3 FA + policosanol 5 or 10 mg/day groups that achieved LDL-C targets or reductions 15% was significantly greater than in the omega-3 FA + placebo group (p < 0.001). Combined therapy with omega-3 FA + policosanol 5 or 10 mg/day resulted in significantly greater changes in LDL-C, TC and HDL-C than treatment with omega-3 FA + placebo, but did not modify the TG response compared with the omega-3 FA + placebo group. Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group). CONCLUSIONS: Policosanol 5 or 10 mg/day administered concomitantly with omega-3 FA 1 g/day improved LDL-C, TC and HDL-C, maintained the reduction in TG attributable to omega-3 FA monotherapy, and was well tolerated. Treatment with omega-3 FA + policosanol could be useful for regulating lipid profile in patients with type II hypercholesterolaemia, but further studies involving larger sample sizes are needed before definitive conclusions can be drawn.     

Effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia associated with type 2 diabetes mellitus

In this pilot, randomized, double-blind study, we compared the effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia and type 2 diabetes mellitus. After 4 weeks on a cholesterol-lowering diet, 36 patients were randomized to policosanol (10 mg/day) or lovastatin (20 mg/day) tablets o.i.d. for 8 weeks. Policosanol significantly (p < 0.001) lowered serum low-density lipoprotein-cholesterol (LDL-C) (29.9%), total cholesterol (21.1%), triglycerides (13.6%) and the LDL-C/high-density lipoprotein-cholesterol (HDL-C) (36.7%) and total cholesterol/HDL-C (28.9%) ratios and significantly (p < 0.01) increased HDL-C (12.5%). Lovastatin significantly (p < 0.001) lowered LDL-C (25%), total cholesterol (18%), triglycerides (10.9%) and the LDL-C/HDL-C (30.4%) and total cholesterol/HDL-C ratios (23.9%) and significantly (p < 0.01) raised HDL-C (8.3%). Policosanol was more effective (p < 0.05) than lovastatin in reducing both ratios and in increasing (p < 0.05) HDL-C. Policosanol, but not lovastatin, significantly raised the lag time (20.9%) of Cu+2-induced LDL peroxidation and total plasma antioxidant activity (24.2%) (p < 0.05). Both policosanol and lovastatin significantly decreased the propagation rate (41.9% and 41.6% respectively, p < 0.001), maximal diene production (8.3% and 5.7%) and plasma levels of thiobarbituric acid reactive substances (9.7% and 11.5%, p < 0.001). Both treatments were well tolerated. Only one patient in the lovastatin group withdrew from the trial due to adverse events. In conclusion, policosanol and lovastatin administered short term to patients with dyslipidemia secondary to type 2 diabetes were effective in lowering cholesterol and in inhibiting the extent of lipid peroxidation. Policosanol (10 mg/day) was slightly more effective than lovastatin (20 mg/day) in reducing the LDL-C/HDL-C and total cholesterol/HDL-C ratios, in increasing HDL-C levels and in preventing LDL oxidation. Nevertheless, since this was a pilot study, further clinical studies performed in larger sample sizes of diabetic patients are needed for definitive conclusions.     

Effects of concurrent therapy with policosanol and omega-3 fatty acids on lipid profile and platelet aggregation in rabbits

BACKGROUND: Policosanol is a mixture of high-molecular-weight aliphatic primary alcohols isolated from sugarcane wax with cholesterol-lowering and antiplatelet effects. Omega-3 fatty acids (FA) from fish oil can protect against coronary disease. An antiarrhythmic mechanism is emerging as the most convincing explanation for omega-3 FA cardiovascular protection, but triglyceride (TG)-lowering effects and inhibition of platelet function could play a role. In view of the effects of policosanol and omega-3 FA on lipid profile and platelet function, potential benefits of combined therapy were expected. OBJECTIVE: To investigate whether combined therapy with policosanol and omega-3 FA would offer some benefit, compared with policosanol or omega-3 FA alone, on serum lipid profile and platelet aggregation in rabbits. METHODS: Male rabbits were randomly distributed in four groups (n = 9 per group). A control group received vehicle, one group was treated with policosanol 5 mg/kg and one with omega-3 FA (eicosapentaenoic acid; EPA [47.0%], docosahexaenoic acid; DHEA [41%]) 250 mg/kg, and the fourth received policosanol 5 mg/kg + omega-3 FA 250 mg/kg. Treatments were orally administered for 60 days. Bodyweight, food consumption and animal behaviour were performed at baseline and study completion. RESULTS: Policosanol significantly lowered low-density lipoprotein cholesterol (LDL-C) [42.7%; p < 0.01] and total cholesterol (TC) [29.4%; p < 0.05], increased high-density lipoprotein (HDL-C) [15.4%; p < 0.05], but left TG levels unchanged. Omega-3 FA significantly lowered TG (47.1%; p < 0.05), but left TC, LDL-C and HDL-C unchanged. Combined therapy decreased LDL-C (38.7%; p < 0.05). Changes in TC, LDL-C and HDL-C obtained with combined therapy were greater (p < 0.05) than those with omega-3 FA, but similar to those with policosanol, whereas the opposite applied to TG reduction. No significant changes in lipid profile were observed in the control group. Policosanol and omega-3 FA significantly (p < 0.05) but moderately inhibited platelet aggregation induced with arachidonic acid (13.3% and 12.4%, respectively); combined therapy achieved greater inhibition (23.9%; p < 0.05). All groups showed similar food consumption and bodyweight gain. No toxic signs were observed in any animal. CONCLUSIONS: Concurrent therapy with policosanol 5 m/kg and omega-3 FA 250 mg/kg lowered LDL-C, TC and TG and increased HDL-C. All treatments inhibited platelet aggregation, but better effects were observed with policosanol + omega-3 FA compared with either treatment alone. Combined therapy was well tolerated. These results suggest that treatment with policosanol + omega-3 FA could be useful for regulating lipid profile and inhibiting platelet aggregation, but conclusive demonstration of such effects requires further experimental and clinical studies.     

多廿烷醇联合阿托伐他汀治疗老年高脂血症的疗效观察

目的探讨多廿烷醇片联合阿托伐他汀钙片治疗老年高脂血症的临床疗效。方法选取2015年2月—2016年5月开滦总医院收治的高脂血症患者180例,根据所用调脂方案分为多廿烷醇组、阿托伐他汀组和联合治疗组,每组各60例,每组各60例。多廿烷醇组晚上口服多廿烷醇片,20mg/次,1次/d。阿托伐他汀组晚上口服阿托伐他汀钙片,20mg/次,1次/d。联合治疗组给予多廿烷醇片和阿托伐他汀钙片,方法同上。所有患者均连续治疗24周。观察两组的临床疗效,比较两组的血脂水平、血小板计数(PLT)和颈动脉内膜中层厚度(IMT)。结果治疗后,多廿烷醇组、阿托伐他汀组和联合治疗组总有效率分别为80.00%、78.33%、93.33%,联合治疗组与多廿烷醇组和阿托伐他汀组比较差异有统计学意义(P0.05)。治疗后,3组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且联合治疗组血脂水平明显低于多廿烷醇组、阿托伐他汀组,3组比较差异有统计学意义(P0.05)。治疗后,3组PLT和IMT没有显著变化,3组比较差异无统计学意义。结论多廿烷醇片联合阿托伐他汀钙片治疗老年高脂血症具有较好的临床疗效,可有效调节血脂水平,安全性较好,具有一定的临床推广应用价值。     

Comparison of the efficacy,safety and tolerability of original policosanol versus other mixtures of higher aliphatic primary alcohols in patients with type II hypercholesterolemia

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol and Octa-60 in patients with type II hypercholesterolemia. After 4 weeks on a diet, 110 patients were randomized to policosanol or Octa-60 5 mg tablets once a day for 5 weeks. The dose was then doubled to 10 mg/day for the next 5 weeks. Policosanol 5 and 10 mg/day significantly lowered low-density lipoprotein-cholesterol (LDL-C) (p<0.0001 and p<0.00001), the main efficacy variable, by 18.6% and 30.2%, while Octa-60 significantly reduced (p<0.05) LDL-C by 10.0% at study completion only. The frequency of policosanol patients reaching reductions of LDL-C > or = 15% after 5 mg/day (37/55; 67.3%) and 10 mg/day (47/55; 88.7%) was greater (p<0.01 and p<0.01) than in the Octa-60 group, which was 5/55 (9.1%) and 20/55 (36.4%). Likewise, the frequency of patients reaching LDL-C values of <3.4 mmol/l at study completion was greater (p<0.001) in the policosanol group (39/55, 70.9%) than in the Octa-60 group (6/55, 10.9%). Policosanol 5 and 10 mg/day significantly lowered (p<0.00001) total cholesterol (TC) (13.4% and 20.4%), LDL-C/high-density lipoprotein-cholesterol (HDL-C) (22.1% and 37.0%) and TC/HDL-C (17.2% and 28.2%). Octa-60 at 10 mg/day lowered (p<0.05) TC (8.7%), LDL-C/HDL-C (12.6%) and TC/HDL-C (9.4%). HDL-C was increased (p<0.001 and 0.0001) by policosanol 5 and 10 mg/day (5.6% and 12.5%) but was unchanged by Octa-60. In both groups, triglycerides remained unchanged. Both treatments were safe and well tolerated. Octa-60, but not policosanol, significantly increased glucose and alanine aminotransferase, but individual values were within the normal range. Four patients (two from each group) discontinued the trial, but only one (in the Octa-60 group) did so because of an adverse event (AE) (skin rash). Overall, three patients (all from the Octa-60 group) reported AEs. In conclusion, original policosanol at 5 and 10 mg/day, but not Octa 60, was effective in patients with type II hypercholesterolemia. Thus, policosanol reached the efficacy criterion for LDL-C reduction in both steps, while Octa-60 failed to reach this goal. In addition, policosanol was better tolerated than Octa-60.     

多廿醇对高脂血症大鼠脂蛋白代谢关键酶活性的影响

目的:研究多廿醇的降胆固醇作用及其酶学机制。方法:将大鼠随机分为对照组、多廿醇(4.0mg·kg-1·d-1)预防组、多廿醇低、中、高剂量(4.0、6.0、8.0mg·kg-1·d-1)组、阳性药洛伐他汀组和高脂模型组(后5组先行高脂造模4周),灌胃给药6周后采集血液,测定血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量;称量大鼠体质量、肝重,计算肝脏系数;测定血清卵磷脂胆固醇酰基转移酶(LCAT)、肝脏脂蛋白脂酶(LPL)和肝脂酶(HL)活性。结果:多廿醇各组能明显降低高脂模型大鼠TC39.1%～43.3%(P<0.01)、LDL-C66.6%～80.7%(P<0.01)、肝脏系数11.1%～11.8%(P<0.01);高剂量组升高HDL-C14.0%(P<0.05),中、高剂量组LCAT活性分别升高41.9%、44.3%(P<0.01),HL活性分别升高20.0%(P<0.05)、28.0%(P<0.01)。结论:多廿醇对高脂模型大鼠具有明显降胆固醇作用,其作用可能与升高脂蛋白代谢关键酶的活性有关。     

ABCG2遗传多态性对阿托伐他汀降脂作用的影响

目的：研究ATP结合盒转运子G2（ABCG2）遗传多态性对阿托伐他汀降脂作用的影响。方法：91例高脂血症患者,给予阿托伐他汀片（10mg／d）治疗8周。分别于治疗前及疗程结束时空腹抽血检测血脂[TC、TG、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]水平。采用焦磷酸测序法对ABCG2进行基因分型。结果：阿托伐他汀能显著降低不同基因型的LDL-C血浆水平（P〈0．01）,且CA、AA型患者降幅较CC型患者显著,差异具有统计学意义（P〈0．05）;阿托伐他汀能显著降低CA、AA型患者的TC、TG血浆水平,差异具有统计学意义（P〈0．05）。结论：ABCG2遗传多态性能影响阿托伐他汀的降脂作用。     

阿托伐他汀与氟伐他汀治疗高胆固醇血症的对比研究

目的　探讨阿托伐他汀 (立普妥 )与氟伐他汀 (来适可 )对高胆固醇血症病人疗效及安全性。方法　 10 0例高胆固醇血症随机分成阿托伐他汀组 5 0例和氟伐他汀组 5 0例 ,治疗 6周后观察比较。结果　阿托伐他汀及氟伐他汀均能明显降低TC、TG、LDL C水平 (P <0 0 1或P <0 0 5 ) ,阿托伐他汀降TC、TG、LDL C的作用强于氟伐他汀 (P <0 0 5 ) ,两药均能升高HDL C水平 (P <0 0 5 ) ,但两组比较未达到显著差异 (P >0 0 5 )。两药不良反应均比较小 ,耐受性好。结论　阿托伐他汀降TC、TG、LDL C的作用优于氟伐他汀 ,但升高HDL C水平相似 ,两药均有良好的安全性。     

阿托伐他汀对血脂异常的非糖尿病病人血清脂联素和糖代谢的影响

目的评价血脂异常的非糖尿病病人给予阿托伐他汀治疗后血清脂联素的变化及对糖代谢的影响。方法 20例血脂异常的非糖尿病患者,给予阿托伐他汀20 mg.d-1,连服12周,于服药前、服药4周和12周时抽取空腹静脉血,分别测定空腹血糖、糖化血红蛋白、胰岛素、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、脂联素。结果用药4周后,患者总胆固醇、低密度脂蛋白胆固醇明显降低(P<0.05),高密度脂蛋白胆固醇明显升高(P<0.05),血清脂联素水平明显升高(P<0.05)。继续服药至12周,总胆固醇、低密度脂蛋白胆固醇进一步下降,所有患者均达到治疗目标,而血清脂联素无明显变化。治疗前后患者空腹血糖、糖化血红蛋白、胰岛素均无明显改变。结论阿托伐他汀治疗后可明显降低总胆固醇、低密度脂蛋白胆固醇,升高血清脂联素水平,对糖代谢无明显影响。     

Effect of Atorvastatin versus Simvastatin on Lipid Profile and Plasma Fibrinogen in Patients with Hypercholesterolaemia: A Pilot, Randomised, Double-Blind, Dose-Titrating Study

OBJECTIVE: To investigate the effect of atorvastatin vs simvastatin on lipid profile and plasma fibrinogen in patients with hypercholesterolaemia. PATIENTS: 30 outpatients (25 men), with a median age of 51 years were studied. Eight patients had established coronary artery disease (CAD) and four had diabetes mellitus at baseline. 11 patients presented a Frederickson's IIb phenotype and 19 a IIa phenotype at baseline. STUDY DESIGN: After a 6-week placebo period, patients were randomly assigned to simvastatin (10 mg/day, n = 15) or atorvastatin (10 mg/day, n = 15). Lipid profile, apolipoproteins B and A-I and plasma fibrinogen were measured for a 16-week period, at 4-week intervals. Thereafter, the dose of each drug was doubled only in patients with low density lipoprotein cholesterol (LDL-C) levels above 130 mg/dl for a further 16-week period. RESULTS: Ten of 15 patients on atorvastatin 10mg (66%) and four of 15 on simvastatin 10mg (27%) achieved the LDL-C <130 mg/dl goal. Apolipoprotein B was reduced by both drugs (-33%, p < 0.001 for atorvastatin and -18%, p < 0.05 for simvastatin), but plasma fibrinogen and triglyceride were reduced only by atorvastatin (-20%, p < 0.01; -36%, p < 0.001, respectively). During the second 16-week period seven of 11 patients receiving the simvastatin 20mg dose (64%) achieved the LDL-C <130 mg/dl goal. The comparison of atorvastatin 10mg with simvastatin 20mg showed that the drugs appear to be equipotent in terms of LDL-C lowering. CONCLUSIONS: Atorvastatin in equipotent doses to simvastatin appeared to be more effective than the latter in reducing triglyceride and plasma fibrinogen in patients with hypercholesterolaemia, mainly in those with Frederickson's phenotype Iib.     

Effect of atorvastatin on high density lipoprotein cholesterol and its relationship with coronary events: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study

OBJECTIVE: To investigate the relationship between changes in high density lipoprotein cholesterol(HDL-C) levels after statin treatment and the risk for coronary heart disease (CHD)-related events in the secondary CHD prevention GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. These findings suggested that dose titration with atorvastatin (10-80 mg/day, mean 24 mg/day)achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality, in comparison to usual care. METHODS: Analysis of variance was used to assess the effect of atorvastatin on HDL-C over time (up to 48 months) in 1600 CHD patients. The time-dependent multivariate Cox predictive model,involving backward stepwise logistic regression,was used to evaluate the relation between coronary events and HDL-C changes. RESULTS: The mean increase in HDL-C levels during the study was 7%. All doses of atorvastatin significantly increased HDL-C levels. Increases were greater in men (7.8 vs 6.1%; p = 0.02), in combined hyperlipidaemia (7.9 vs 6.4% for hypercholesterolaemia; p = 0.04), and in the lower baseline HDL-C quartile (9.2 vs 5.3%, 1st vs 4th quartile; p = 0.001). After adjustment for 24 predictors of coronary events, multivariate analysis revealed a Hazards Ratio of 0.85 (95% confidence interval 0.76-0.94; p = 0.002) for every 4 mg/dL(0.1 mmol/L) increase in HDL-C. CONCLUSIONS: There was a significant beneficial effect on HDL-C levels across the dose range of atorvastatin. Clinical outcomes in the structured care arm of GREACE were determined in part by the extent of atorvastatin-induced HDL-C increase.This effect was independent from benefit induced by low density lipoprotein cholesterol (LDL-C)reduction, suggesting that the CHD risk reduction associated with a rise in a low HDL-C at baseline remains significant under aggressive (-46%) LDL-C lowering conditions. However, the relationship between HDL-C and vascular risk may be weaker when LDL-C levels are aggressively lowered.     

多廿醇对高脂血症大鼠血清胆固醇水平的影响

目的观察多廿醇对高脂血症大鼠的降胆固醇作用并探讨其作用机制。方法大鼠分为正常对照组、多廿醇4mg.kg-1预防组、高脂模型组、多廿醇4,6和8mg.kg-1治疗组和洛伐他汀阳性对照组;后5组大鼠在实验前4周给予高脂饲料制备高脂大鼠模型,从第5周开始,除正常对照和高脂模型组外,各给药组ig给予不同浓度的多廿醇或洛伐他汀,每天1次,连续6周。多廿醇预防组喂饲高脂饲料的同时ig多廿醇,每天1次,连续10周。用全自动生化分析仪测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,并测定粪便总胆汁酸(FBA)排出量,紫外分光速率法测定肝脏微粒体3-羟基-3-甲基戊二酸单酰辅酶A(HMG-CoA)还原酶活性,荧光配体标记法测定外周血淋巴细胞低密度脂蛋白受体(LDL-R)活性。结果与高脂模型组比较,多廿醇预防组、多廿醇治疗组和洛伐他汀阳性对照组大鼠血清TC含量明显下降(39.1%～46.4%),LDL-C含量明显下降(66.6%～80.7%),粪便FBA明显升高(9.7%～19.0%),肝脏微粒体HMG-CoA还原酶活性明显下降(13.8%～23.6%),外周血淋巴细胞LDL-R活性升高(27.5%～129.6%);多廿醇预防组、多廿醇8mg.kg-1组和洛伐他汀组HDL-C水平明显升高(12.2%～16.7%);洛伐他汀组TG水平明显下降。结论多廿醇具有明显降低胆固醇的作用,其机制包括增加胆汁酸的排泄、抑制胆固醇合成限速酶HMG-CoA还原酶活性和促进低密度脂蛋白受体活性的表达。     

普罗布考联合阿托伐他汀对急性冠脉综合征血脂蛋白相关磷脂酶A2的影响

目的:评价普罗布考和阿托伐他汀联合应用对急性冠脉综合征(ACS)患者血脂及脂蛋白相关磷脂酶A2(Lp-PLA2)的影响.方法:将94例经冠脉造影证实的ACS患者随机分为2组:单药组48例,予以阿托伐他汀(20 mg/d)治疗;联合组46例,予以阿托伐他汀(20 mg/d)和普罗布考(500 mg/d)联合治疗.分别于治疗前和治疗后6～8周检测血Lp-PLA2和血总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平并进行比较分析.结果:2组治疗前TC、TG、LDL-C、HDL-C、Lp-PLA2水平比较差异无统计学意义(P＞0.05);2组治疗后TC、TG、LDL-C、Lp-PLA2较治疗前均降低,单药组治疗后HDL-C升高,联合组治疗后HDL-C下降,差异均有统计学意义(P＜0.01);联合组较单独治疗组治疗后TC、LDL-C、Lp-PLA2降低,差异均有统计学意义(P＜0.05),但TG差异无统计学意义(P＞0.05).结论:对ACS患者单独应用阿托伐他汀及联合普罗布考均能够有效降低TC、LDL-C、Lp-PLA2,但联合治疗疗效更为显著,对稳定斑块、抗动脉粥样硬化有重要意义.     

LDL-C/HDL-C ratio in subjects with cardiovascular disease and a low HDL-C: results of the RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study

BACKGROUND: The ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (LDL-C/HDL-C) is a reliable predictor of cardiovascular risk. Low HDL-C levels in patients with coronary artery disease are associated with a high risk for cardiovascular events. OBJECTIVES: This study compared the effects of rosuvastatin and atorvastatin on the LDL-C/HDL-C. METHODS: Patients aged 40-80 years with established cardiovascular disease and HDL-C < 1.0 mmol/L (< 40 mg/dL) entered as a 6-week dietary run-in period, before randomisation to open-label treatment with rosuvastatin 10 mg (n = 230) or atorvastatin 20 mg (n = 231) for 6 weeks. Doses were increased after 6 weeks to rosuvastatin 20 mg or atorvastatin 40 mg, and after 12 weeks to rosuvastatin 40 mg or atorvastatin 80 mg. Serum lipid parameters were measured at baseline and 6, 12 and 18 weeks. RESULTS: After 6 weeks of treatment, mean percentage change from baseline in LDL-C/HDL-C ratio was -47.0% in the rosuvastatin group and -41.9% in the atorvastatin group (p < 0.05 for between-group comparison). After 12 and 18 weeks of treatment, change from baseline was -53.0% and -57.3%, respectively, for rosucastatin, compared with -47.9% and -49.6%, respectively, for atorvastatin (p < 0.01 and p < 0.001, respectively, for between-group comparison). Rosuvastatin also reduced LDL-C, total cholesterol/HDL-C significantly more than atorvastatin at all three time points, and significantly improved total cholesterol/HDL-C and apolipoprotein B/A-I ratios. CONCLUSIONS: Rosuvastatin 10, 20 and 40 mg is significantly more effective than atorvastatin 20, 40 and 80 mg, respectively, in improving the LDL-C/HDL-C ratio in patients with cardiovascular disease and low HDL-C. Further studies are required to clarify the benefits of rosuvastatin for reduction of cardiovascular risk.     

Concomitant use of policosanol and beta-blockers in older patients

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. It is safe and well tolerated, even in populations with high consumption of concomitant drugs. These data suggest that adverse events (AE) due to drug-to-drug interactions (DDI) with policosanol are not relevant. Experimental data indicate that potential DDI between policosanol and drugs metabolized through the cytochrome P450 hepatic system are not expected, but pharmacodynamic DDI cannot be excluded. Several clinical studies have shown that policosanol decreased arterial pressure compared with placebo, and a pharmacological interaction with beta-blockers was experimentally proven. Therefore, clinical DDI between policosanol and beta-blockers can be expected. This study investigated whether policosanol reinforces the antihypertensive effects of beta-blockers and/or whether this combination impairs some safety indicators or induces specific AE in older patients. After 5 weeks on a diet-only baseline period, 205 older hypercholesterolemic patients taking beta-blockers were randomized to policosanol 5 mg/day or placebo for 3 years. After 1 year on therapy, policosanol significantly reduced (p < 0.00001 versus placebo) low-density lipoprotein-cholesterol (LDL-C) (20.9%), total cholesterol (TC) (19.3%) and triglycerides (TG) (25.7%), whereas it increased (p < 0.01 and p < 0.001 versus placebo) high-density lipoprotein-cholesterol (HDL-C) levels (4.1%). Treatment effects did not to wear off during the 3-year follow-up. At study completion, policosanol lowered (p < 0.00001 versus placebo) LDL-C (34.3%), TC (23.2%) and TG (21.2%) and raised (p < 0.00001 versus placebo) HDL-C (12.3%). Thirty-one patients (15.1%) discontinued the study, 22 in the placebo group (20.6%) and nine in the policosanol group (9.2%). Of these, 20 patients (16 in the placebo group and four in the policosanol group) withdrew from the study due to AE. The frequency of serious adverse events (SAE), mostly vascular, in policosanol patients (3/98, 3.1%) was lower than in the placebo group (15/107, 14.0%). No impairment of safety indicators was observed. Nevertheless, reductions in systolic and diastolic blood pressure were observed in policosanol patients compared with those in the placebo group. The frequency of policosanol patients reporting mild or moderate AE (18/98, 18.4%) was also lower than in the placebo group (30/107, 28.0%). In conclusion, policosanol was well tolerated in elderly patients taking beta-block- ers and did not increase AE. Additional reduction of blood pressure and a lower frequency of SAE were observed in policosanol patients compared with those taking placebo. The cholesterol-lowering efficacy of policosanol was that expected. These results provide support that policosanol therapy added to hypercholesterolemic elderly individuals taking beta-blockers could provide additional benefits in lowering blood pressure; SAE were not more frequent in the policosanol group than in the placebo group and there was no increase in AE.     

Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol (10 mg/day) and lovastatin (20 mg/day) in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. After 6 weeks on a lipid lowering diet, 53 patients were randomized to receive either policosanol or lovastatin tablets that were taken o.i.d. for 12 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly (p < 0.001) lowered low-density lipoprotein (LDL)-cholesterol (20.4%), total cholesterol (14.2%) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (23.7%). Lovastatin significantly (p < 0.01) lowered LDL-cholesterol (16.8%), total cholesterol (14.0%) and the ratio (p < 0.05) of LDL-cholesterol to HDL-cholesterol (14.9%). Triglyceride levels did not significantly change after therapy. Policosanol, but not lovastatin, significantly increased (p < 0.01) levels of HDL-cholesterol (7.5%). Comparison between groups showed that changes in HDL-cholesterol induced by policosanol were significantly greater (p < 0.01) than those induced by lovastatin. Both treatments were safe and well tolerated. Lovastatin moderately but significantly (p < 0.05) increased levels of aspartate aminotransferase, creatine phosphokinase and alkaline phosphatase. Adverse reactions were more frequent in the lovastatin group (p < 0.01) than in the policosanol group. In conclusion, policosanol administered at 10 mg/day produces more advantageous changes in HDL-cholesterol and has a better safety and tolerability profile than lovastatin 20 mg/day.     

阿托伐他汀对急性脑梗死调脂及MMP-9影响的观察

目的观察阿托伐他汀对急性脑梗死患者调脂及人单核细胞基质金属蛋白酶-9（MMP-9）的影响。方法60例急性脑梗死患者给予阿托伐他汀20mg,口服,1次/d,疗程4周。观察治疗前后血脂和血清MMP-9的变化。结果经阿托伐他汀治疗4周后,TC、LDL—C较治疗前均明显降低,HDL—C较治疗前明显升高,且明显优于对照组（P〈0．05和0．01）,血清MMP-9水平显著降低（P〈0．01）。结论阿托伐他汀不仅具有调脂作用,还明显降低MMP-9的作用。     

Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro

AIMS: The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers. METHODS: The effect of policosanol (5 and 10 mg day(-1) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conducted in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks were subjected to in vitro tests of LDL-C oxidation. We tested the susceptibility of LDL-C to lipid peroxidation in a cell-free system by the addition of copper ions as well as in a more physiological system, macrophage-mediated oxidation. RESULTS: At baseline all groups were well matched regarding all variables. After 8 weeks of therapy policosanol administered at 5 and 10 mg, significantly and in a dose-dependent manner increased the lag phase of conjugated diene generation (mean +/- s.d.) from 83.79+/-29.16 min to 94.90+/-25.50 min (5 mg day(-1)) and from 82.74+/-17.16 min to 129.89+/-35.71 min (10 mg day(-1)), while in the placebo group LDL-C oxidation did not change significantly. Policosanol (10 mg day(-1)), but not placebo, significantly decreased the rate of conjugated diene generation. Comparison with placebo after therapy also showed significant differences. Macrophage mediated-oxidation was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day(-1)) significantly lowered malondialdehyde (MDA) generation from 8.50+/-0.91 to 5.76+/- 1.01 nmol mg(-1) protein. Comparison with placebo after 5 and 10 mg day(-1) showed significant differences. Policosanol significantly lowered total cholesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day(-1)) increased HDL-C by 15.2%. Five subjects withdrew from the study, none because of adverse experiences. No clinical or blood biochemical drug-related disturbances were found. CONCLUSIONS: The present study demonstrated that policosanol administered within its therapeutic dosage for lowering cholesterol (5 and 10 mg day(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.     

Effect of short term treatment with simvastatin and atorvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia

OBJECTIVE: High-density lipoprotein (HDL)-associated paraoxonase (PON) activity may play an important role in the inhibition of low-density lipoprotein (LDL) oxidation. Previous studies have demonstrated that serum PON activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease. The study presented here examined the effect of short-term treatment with simvastatin and atorvastatin on lipids and PON activity in patients with hyperlipoproteinaemia. RESEARCH DESIGN AND METHODS: A prospective, non-blinded, single-group, cross-over, comparative trial was performed. Following an 8-week dietary run-in period, 49 patients (23 men and 26 women, mean age: 59.8 +/- 7.9 years) with Fredrickson type IIa. and IIb. hyperlipoproteinaemias were randomized to receive either simvastatin 20 mg/day or atorvastatin 10 mg/day for 3 months. Following an 8-week washout period, patients were crossed-over to receive the other drug for a further 3 months. Serum lipids were measured and serum PON activity was determined spectrophotometrically using paraoxon as a substrate. RESULTS: Simvastatin treatment significantly reduced serum cholesterol, LDL-cholesterol (LDL-C) and apolipoprotein (apo) B levels (p < 0.001). Atorvastatin had a more pronounced cholesterol, LDL-C- and apo B-lowering effect (p < 0.001) compared with simvastatin. Both statins also significantly reduced serum triglyceride levels (p < 0.01). Simvastatin and atorvastatin caused no significant change in the levels of HDL-cholesterol (HDL-C) and apo A1. HDL-associated PON activity did not change significantly after simvastatin therapy, but significantly increased after atorvastatin treatment (p < 0.05). CONCLUSIONS: Short-term administration of simvastatin did not increase PON activity. Atorvastatin treatment had a favourable effect on lipid profile and increased the activity of HDL-associated PON.     

阿托伐他汀对急性脑梗死调脂及MMP-9影响的观察

目的 观察阿托伐他汀对急性脑梗死患者调脂及人单核细胞基质金属蛋白酶-9(MMP-9)的影响.方法 60例急性脑梗死患者给予阿托伐他汀20mg,口服,1次/d,疗程4周.观察治疗前后血脂和血清MMP-9的变化.结果 经阿托伐他汀治疗4周后,TC、LDL-C较治疗前均明显降低,HDL-C较治疗前明显升高,且明显优于对照组(P<0.05和0.01),血清MMP-9水平显著降低(P<0.01).结论 阿托伐他汀不仅具有调脂作用,还明显降低MMP-9的作用.