A comparative crossover study of the effects of fluvastatin and pravastatin (FP-COS) on circulating autoantibodies to oxidized LDL in patients with hypercholesterolemia

This study compared the effects of fluvastatin and pravastatin on the in vivo oxidation of LDL in a crossover design to evaluate whether or not it is justified to switch between the two statins with regard to serum levels of lipids, lipoproteins, and apolipoproteins (apo), and circulating autoantibodies to oxidized LDL (OxLDL-Ab). Patients with hypercholesterolemia (n = 46) were randomly assigned into groups who received fluvastatin (20 mg/d) or pravastatin (10 mg/d). After 3 months, they were crossed to receive the other statin for another 3 months. Circulating levels of OxLDL-Ab were measured by an OxLDL IgG ELISA test. Fluvastatin and pravastatin similarly decreased serum levels of total cholesterol (TC), LDL-C, and apo B, and increased HDL(2)-C levels. After crossover to the other statin, these lipid parameters were not further changed by either statin. Before crossover, circulating levels of OxLDL-Ab were decreased in patients with fluvastatin treatment, but not in those with pravastatin treatment. After switching from the other statin, both fluvastatin and pravastatin further decreased OxLDL-Ab levels. In conclusion, fluvastatin at 20 mg/d and pravastatin at 10 mg/d are similar with regard to their efficacy in decreasing TC, LDL-C, and apo B levels and increasing HDL(2)-C levels. Fluvastatin lowered circulating levels of OxLDL-Ab, and these effects continued after switching to pravastatin.     

老年患者应用不同类型他汀类药物的疗效及安全性评价

目的观察不同剂量和类型他汀类药物在老年高脂血症患者中应用的疗效与安全性。方法回顾性分析456例老年高脂血症患者服用他汀类药物情况,根据服药情况分为:阿托伐他汀组(169例)、辛伐他汀组(110例)、普伐他汀组(137例)和氟伐他汀组(40例);又根据《中国成人血脂异常防治指南》将患者分为中危(41例)、高危(232例)和极高危(183例)。观察治疗8周后血脂水平及不良反应。结果与治疗前比较,阿托伐他汀组、辛伐他汀组、普伐他汀组和氟伐他汀组治疗8周后血清TC、LDL-C水平均明显降低(P0.05,P0.01)。4组治疗前后血清TG水平差异无统计学意义(P0.05)。阿托伐他汀组、辛伐他汀组治疗8周后血清TC、LDL-C变化率与普伐他汀组、氟伐他汀组比较差异有统计学意义(P0.05)。各组中高危患者服用标准剂量他汀类药物治疗后,LDL-C达标率均在80%以上,极高危患者达标率为44.1%～55.7%。结论多数老年高脂血症患者服用小剂量和(或)标准剂量他汀类药物血脂即可达标。且治疗安全性好,无严重不良反应发生。     

Statins: effective antiatherosclerotic therapy

BACKGROUND: Statins are the most effective agents currently available for lowering plasma levels of low-density lipoprotein cholesterol (LDL-C) and are the mainstay of therapy for hyperlipidemia. The statins are highly liver-selective, inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a key enzyme in the synthesis of cholesterol. Several large, controlled clinical trials have confirmed significant reductions in rates of coronary heart disease morbidity and death with long-term statin therapy in patients with mild to severe hypercholesterolemia. METHODS AND RESULTS: This review article is based on a literature search of more than 60 relevant articles from peer-reviewed journals. Search engines included Medline and Embase. In surveying clinical and angiographic evidence, we found that statins appear to reduce the incidence of coronary events by slowing the progression of atherosclerosis and preventing atheromatous lesion formation. We found that the 6 statins currently marketed-atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin-differ in their inhibitory action on the HMG-CoA reductase enzyme. CONCLUSIONS: The use of more potent statins such as atorvastatin and simvastatin affords greater lowering of LDL-C and triglyceride levels, allowing more patients to achieve target goals. The question of how low LDL-C levels should be lowered will be answered by ongoing clinical trials.     

依折麦布联合普伐他汀治疗高胆固醇血症患者的疗效

目的探索依折麦布联合普伐他汀治疗高胆固醇血症的临床疗效。方法选择符合高胆固醇血症的患者180例,男女各90例,在合理的饮食、生活习惯和体育运动下,分为三组,每组男女平衡：A组为单用依折麦布治疗组60例：B组为单用普伐他汀治疗组60例;C组为依折麦布联合普伐他汀治疗组60例。观察三组血清总胆固醇（total cholesterol,TC）、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL-C）、高密度脂蛋白胆固醇（high—density lipoprotein cholesterol,HDL—C）、载脂蛋白B（apoprotein B,Apo—B）及三酰甘油（triacylglycerol,TG）等治疗前、后的变化,并记录不良反应。结果三组治疗后血清TC、LDL—C、Apo-B、TG浓度均能降低,血清HDL—C浓度均能升高,但以C组更明显（P〈0．05）;C组总有效率达91．7％,优于A、B组。结论依折麦布联合普伐他汀具有良好的药物协同效应,可有效调节胆固醇代谢,效果明显优于单独使用,可避免大剂量他汀类药物的不良反应。     

Comparing the effects of five different statins on the HDL subpopulation profiles of coronary heart disease patients

We compared the effects of five different statins (atorvastatin, simvastatin, pravastatin, lovastatin, and fluvastatin) on the lipid, lipoprotein, and apolipoprotein (apo) A-I-containing high-density lipoprotein (HDL) subpopulation profiles of 86 coronary heart disease (CHD) patients. Patients with established CHD, and low density lipoprotein (LDL) cholesterol (C)>130 mg/dl, and triglyceride (TG)<400 mg/dl, were treated with atorvastatin 20, 40, and 80 mg/day and one of the other four statins at 20, 40, and when available 80 mg/day in increasing doses (4 weeks of each dose) in a randomized crossover fashion. There was an 8-week placebo controlled washout period between different drug treatments. All five statins on each dose resulted in significant reductions in total- and LDL-C compared to placebo treatment. There were also decreases in plasma TG and increases in HDL-C and apoA-I concentrations, but not all treatments changed these parameters significantly. Each statin except fluvastatin improved the HDL subpopulation profile by increasing the concentrations of the large, cholesterol-rich, LpA-I alpha-1 and prealpha-1 HDL subpopulations. CHD patients have significantly lower concentration of the large, LpA-I alpha-1 HDL particles compared to controls. Our data indicate that statins which are the most effective in lowering LDL-C and TG are also the most effective agents in modifying the HDL subpopulation profile in CHD patients towards the patterns found in healthy individuals. The order of efficacy of statins in increasing alpha-1 HDL subpopulation was: atorvastatin, simvastatin, pravastatin, lovastatin and fluvastatin.     

Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects

The effects of atorvastatin at 20, 40, and 80 mg/day on plasma lipoprotein subspecies were examined in a randomized, placebo-controlled fashion over 36 weeks in 97 patients with coronary heart disease (CHD) with low-density lipoprotein (LDL) cholesterol levels of >130 mg/dl and compared directly with the effects of fluvastatin (n = 28), pravastatin (n = 22), lovastatin (n = 24), and simvastatin (n = 25). The effects of placebo and 40 mg/day of each statin were also examined in subjects with CHD with subjects in the fasting state and in the fed state 4 hours after a meal rich in saturated fat and cholesterol and compared with results in age- and gender-matched control subjects. At all doses tested in the fasting and fed states, atorvastatin was significantly (p <0.01) more effective in lowering LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol than all other statins, and significantly (p <0.05) more effective than all statins, except for simvastatin, in lowering triglyceride and remnant lipoprotein (RLP) cholesterol. At 40 mg/day in the fasting state, atorvastatin was significantly (p <0.01) more effective than all statins, except for lovastatin and simvastatin, in lowering cholesterol levels in small LDL, and was significantly (p <0.05) more effective than all statins, except for simvastatin, in increasing cholesterol in large HDL and in lowering LDL particle numbers. Our data indicate that atorvastatin was the most effective statin tested in lowering cholesterol in LDL, non-HDL, and RLP in the fasting and fed states, and getting patients with CHD to established goals, with fluvastatin, pravastatin, lovastatin, and simvastatin having about 33%, 50%, 60%, and 85% of the efficacy of atorvastatin, respectively, at the same dose in the same patients.     

A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia

Pitavastatin (p-INN) is a novel and fully synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, with a cholesterol-lowering action stronger than that of other statins currently in use. A 12-week, multi-center, randomized, double-blind, controlled study was conducted to confirm the efficacy and safety of pitavastatin compared with pravastatin, an agent for using to reduce low density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. Patients were recruited at 43 institutes in Japan. Following more than 4 weeks run-in period, 240 patients were randomized to receive 2 mg of pitavastatin or 10 mg of pravastatin daily. At 12 weeks post-randomization, the pitavastatin group showed significantly lower LDL-C levels by -37.6% from baseline compared with -18.4% in the pravastatin group (P<0.05). Pitavastatin also significantly lowered total cholesterol (TC) by -28.2% compared with -14.0% of pravastatin (P<0.05). The LDL-C target level of <140 mg/dl was attained in 75% of the patients treated with pitavastatin, compared with 36% of those in the pravastatin group (P<0.05). Pitavastatin also significantly reduced triglycerides (TG), apo B, C-II and C-III, compared with pravastatin, and increased HDL-C, apo A-I and A-II, to the same extent of pravastatin. Safety was assessed by monitoring adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. These results indicated that pitavastatin was more effective than pravastatin, and both drugs were well-tolerated in the treatment of hypercholesterolemia.     

More Western hypercholesterolemic patients achieve Japan Atherosclerosis Society LDL-C goals with rosuvastatin therapy than with atorvastatin, pravastatin, or simvastatin therapy.

BACKGROUND: Data from Western comparative trials suggest that rosuvastatin is more effective than atorvastatin, simvastatin, and pravastatin in helping hypercholesterolemic patients achieve US and European lipid-lowering guidelines. The purpose of this analysis was to assess the comparative efficacy of rosuvastatin in reducing low-density lipoprotein cholesterol (LDL-C) to levels recommended by the Japan Atherosclerosis Society (JAS). METHODS AND RESULTS: A post hoc analysis of data from 6 randomized, double-blind, active-controlled trials was conducted to evaluate the relative efficacy of rosuvastatin and comparator statins in helping patients achieve the LDL-C goals established by the JAS. The first 5 trials, prospectively designed for pooling, were originally conducted to compare the effects of rosuvastatin with either atorvastatin, simvastatin, or pravastatin in reducing lipid levels and helping patients achieve the LDL-C goals established by the National Cholesterol Education Program. The 6th trial was conducted with similar objectives, but in patients with heterozygous familial hypercholesterolemia (HeFH). Data from 2,139 hypercholesterolemic patients in the first 5 trials were pooled for analysis: rosuvastatin 5 mg (n=390) or 10 mg (n=389) vs atorvastatin 10 mg (n=393); rosuvastatin 5 mg (n=240) or 10 mg (n=226) vs simvastatin 20 mg (n=249) or pravastatin 20 mg (n=252). In the studies with atorvastatin as the comparator, JAS-defined LDL-C goals were reached by 67.2% of the rosuvastatin 5-mg group, 82.3% of the rosuvastatin 10-mg group, and 58.0% of the atorvastatin 10-mg group (p<0.001 for both rosuvastatin groups vs atorvastatin) at 12 weeks. Similarly, in the trials with pravastatin and simvastatin as comparators, the JAS LDL-C goals were reached by 77.5% of the rosuvastatin 5-mg group, 86.7% of the rosuvastatin 10-mg group, 45.2% of the pravastatin 20-mg group and 65.5% of the simvastatin 20-mg group (p<0.001 for both rosuvastatin groups vs pravastatin and simvastatin). In the trial of HeFH patients (n=433 for rosuvastatin, n=187 for atorvastatin), 31.9% of patients treated with rosuvastatin 20 mg achieved JAS LDL-C goals, compared with 17.6% of patients treated with atorvastatin 20 mg (p<0.001). CONCLUSIONS: Rosuvastatin has demonstrated clinical superiority over atorvastatin, pravastatin, and simvastatin in reducing LDL-C levels and in enabling patients to reach goals established by the JAS.     

Usefulness of hydrophilic vs lipophilic statins after acute myocardial infarction: subanalysis of MUSASHI-AMI.

BACKGROUND: Statins are widely used to reduce blood levels of low-density lipoprotein-cholesterol (LDL-C). Each statin has unique pharmacokinetic properties; lipophilicity is one such property and relates to tissue selectivity. METHODS AND RESULTS: The Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors in Patients with Acute Myocardial Infarction (MUSASHI-AMI) trial evaluated the effect of discretional statin treatment initiated within 96 h after onset of acute myocardial infarction (AMI) in Japanese patients. To clarify whether statin lipophilicity affects prognosis, a post hoc analysis of the MUSASHI-AMI database was performed. Patients who were assigned to receive statin were separated into 2 groups according to the lipophilicity of the statins they were administered: lipophilic statins (atorvastatin, fluvastatin, pitavastatin and simvastatin; LS group; n=131) or hydrophilic statins (pravastatin; HS group; n=110). There was no difference in baseline LDL-C concentrations between the 2 groups. Although LDL-C was decreased more potently in the LS than HS groups (-34% vs -19%; p=0.0069), acute coronary syndrome events tended to occur less frequently (3.6% vs 9.9%; p=0.0530) and the incidence of new Q-wave appearance in electrocardiogram was significantly lower (75% vs 89%; p=0.0056) in the HS than LS groups. CONCLUSIONS: In normocholesterolemic Japanese patients after AMI, hydrophilic pravastatin could be superior to lipophilic statins at preventing new Q-wave appearance and reducing cardiovascular events.     

Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia

Plasma cholesterol and other lipoproteins play a significant role in the development of atherosclerosis and subsequent coronary heart disease (CHD). This 1 year study was designed to confirm the efficacy and safety of atorvastatin (Lipitor) compared to pravastatin, a marketed agent for low density lipoprotein cholesterol (LDL-C) reduction in hypercholesterolemic patients. Patients were recruited at 26 centers in six European countries. After a 6 week placebo baseline phase, patients were randomized to receive atorvastatin 10 mg or pravastatin 20 mg daily. The dose could be doubled at week 16, if LDL-C levels remained ≥3.4 mmol/l (135 mg/dl). Atorvastatin significantly lowered LDL-C from baseline by 35% compared with 23% for pravastatin (P<0.05). A total of 72% of atorvastatin patients attained the LDL-C target level of <3.4 mmol/l, compared to 26% of pravastatin patients. Atorvastatin also significantly reduced TC, TG and apo B (P<0.05). Safety was assessed by recording adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. Atorvastatin 10 and 20 mg once daily is superior to pravastatin 20 and 40 mg once daily in treating patients with hypercholesterolemia.     

The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia

OBJECTIVES

The goal of this study was to determine the long-term effects of statins and antioxidant vitamins on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia.

BACKGROUND

Lipid-lowering therapy and antioxidant vitamins improve endothelium-dependent vasodilation in young and middle-aged adults with hypercholesterolemia, but their effects in older adults are not known.

METHODS

Two double-blind, placebo-controlled studies were performed in individuals ≥70 years old with low-density lipoprotein cholesterol (LDL-C) ≥140 mg/dl. In the first study, 37 subjects were randomized to receive (group 1) pravastatin for six months then pravastatin and vitamin E for six additional months or (group 2) vitamin E for six months, then pravastatin and vitamin E for six additional months. In the second study, additional 17 subjects sequentially received simvastatin for six months, then simvastatin and vitamins C and E for six additional months. Flow-mediated vasodilation of the brachial artery was measured by high-resolution ultrasound.

RESULTS

At baseline, subjects in both studies were similar in age (mean ± SD, 75.8 ± 4.2 years), gender, systolic blood pressure, total cholesterol (261.6 ± 37.4 mg/dl), LDL-C (180.3 ± 28.1 mg/dl), high-density lipoprotein cholesterol and triglycerides levels. Flow-mediated vasodilation was severely impaired (2.2 ± 3.9%). Both statins reduced total and LDL-C levels (p < 0.001); however, neither statin, antioxidant vitamin regimen nor the combination of statins and antioxidant vitamins improved flow-mediated vasodilation of the brachial artery. At baseline, nitroglycerin-mediated vasodilation also was impaired (10.7 ± 5.6%) and did not change in either study.

CONCLUSIONS

Older adults with hypercholesterolemia have impaired flow-mediated vasodilation of the brachial artery that does not improve after one year of therapy with statins and antioxidant vitamins, despite significant lipid-lowering.     

冠状动脉支架置入术1年随访LDL-C控制及他汀使用情况:与新指南的距离

目的分析冠状动脉支架置入术后1年随访时低密度脂蛋白胆固醇(LDL-C)控制及他汀使用情况,并与新指南对照。方法入选2010年9月至2012年12月在解放军第三〇六医院心血管内科行冠状动脉支架置入术患者539例,随访1年,收集复查资料,包括LDL-C水平及生化指标以及他汀类药物使用情况。结果治疗1年后,按2004年ACC/AHA血脂指南LDL-C水平,达标373例(69.2%),未达标166例(30.8%)。按2013年ACC/AHA新指南评价,LDL-C水平达标195例(36.1%),未达标344例(63.9%)。两种标准评价是否一致Kappa值为-0.047,P=0.178,两种标准比较存在明显统计学差异。他汀类药物治疗以阿托伐他汀(n=247,10 mg~80 mg)和瑞舒伐他汀(n=147,5 mg~20 mg)为主,其他还包括辛伐他汀(n=139,25.7%,10 mg~40 mg),氟伐他汀(n=2,40 mg),普伐他汀(n=4,40mg)。根据新指南中他汀类药物治疗强度,本研究中低强度降脂治疗21例(4.0%),中等强度512例(94.9%),高强度6例(1.1%),43例联合普罗布考治疗。结论按2013年新指南,冠状动脉支架置入术后他汀治疗1年,随访时多数患者LDL-C不达标,新指南是否适合中国人群需要进一步研究。     

Primary prevention of cardiovascular diseases among hypercholesterolemic Japanese with a low dose of pravastatin

The MEGA Study was Japan's first primary prevention trial of cardiovascular disease (CVD) by cholesterol lowering with low-dose pravastatin. Included were postmenopausal women aged < or =70 years and men aged 40-70 years with mildly elevated total cholesterol (TC) level 220-270 mg/dL. In all, 8214 outpatients were randomly assigned to receive diet alone or diet plus pravastatin 10-20mg/day for an average follow-up of 5.3 years. The primary endpoint was a composite of fatal and nonfatal MI, angina, cardiac and sudden death, and coronary revascularization. TC was reduced by 11.5% in the diet plus pravastatin group versus 2.1% in the diet alone group. LDL-C was reduced by 18% and 3.2% in the two groups, respectively. TC was reduced to <220 mg/dL and LDL-C to <130 mg/dL in patients in the diet plus pravastatin group. There was a significant 33% reduction of the primary endpoint in the diet plus pravastatin group compared with the diet alone group. Notable findings of the MEGA Study included the observation that despite pravastatin's modest LDL-C reductions in this low-risk population, a 33% reduction of CHD events was achieved. Even though 68% of patients were women, who have been traditionally considered at less risk than men, significant CHD risk reduction was observed across all groups.     

Comparative study between high-dose fluvastatin and low-dose fluvastatin and ezetimibe with regard to the effect on endothelial function in diabetic patients

It is well established that statins improve the prognosis of patients with coronary artery disease. However, it is still unclear whether the protective effects of statins relate to lipid lowering alone or whether other pleiotropic effects may contribute. Thus, we compared the endothelial function among two groups of diabetic patients treated with fluvastatin 60 mg (F60) or fluvastatin 20 mg combined with ezetimibe 10 mg (F20/E10). The endothelial function was evaluated by measuring flow-mediated vasodilatation (FMD) at baseline and follow-up at 10 weeks. Similar improvements in FMD were observed in the two groups. The reduction in low-density lipoprotein cholesterol (LDL-C) was less pronounced in the F60 group, compared with the F20/E10 group. A significant reduction in remnant-like lipoprotein particles cholesterol (RLP-C) was observed in the F20/E10 group, but not in the F60 group. A correlation between the observed reduction in LDL-C or RLP-C and the improvement in FMD was observed in F20/E10 group. These results suggest that high-dose fluvastatin might have pleiotropic effects of potential clinical benefit, and that the combination of ezetimibe with a reduced dose of fluvastatin may also significantly improve endothelial function with reduction of LDL-C and RLP-C.     

Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin

The aim of the present study was to investigate plasma levels of asymmetric dimethylarginine (ADMA), an important endogenous inhibitor of nitric oxide synthase, in populations at high risk for atherosclerosis as compared to healthy controls, and furthermore to evaluate the effect of cholesterol lowering therapy in individuals with hypercholesterolemia. The present study consisted of 32 men with untreated hypercholesterolemia (HC group), 38 individuals with well-controlled insulin-dependent diabetes mellitus (DM group) and 20 healthy individuals (controls). The HC subjects were randomly allocated into a double blinded, placebo-controlled cross-over designed study with 8 weeks treatment with pravastatin (40 mg/day) or matching placebo. ADMA levels were statistically significantly higher in DM and HC individuals as compared to controls (P<0.001 for both), and the L-arginine/ADMA ratios were significantly lower in both groups (P<0.001 and P<0.005, respectively). Significant reductions in total cholesterol (TC) and LDL-C levels on pravastatin were obtained (P<0.001 for both), whereas no changes were observed in the levels of ADMA or the L-arginine/ADMA ratios. Statistically significant correlations between ADMA and TC and LDL-C were found (r=0.41, P<0.001 for both). In conclusion, significantly elevated ADMA levels and reduced L-arginine/ADMA ratios were found in individuals with diabetes type-1 as well as in hypercholesterolemia. Treatment with pravastatin 40 mg/day for 8 weeks had no effect on the levels of ADMA in hypercholesterolemic men.     

118例高胆固醇血症患者调脂治疗达标情况分析

目的 调查高胆固醇血症患药物治疗达标率。方法 对现行调脂治疗持续时间≥2个月的118例高胆固醇血症患进行血脂检查,并根据1997年我国制定的《血脂异常防治建议》确定血脂是否达标。结果 总胆固醇（TC）和低密度脂蛋白胆固醇（LDL－C）总达标率分别为23．7％、38．1％,他汀类药物LDL－C总达标率高于海鱼油和绞股兰每日20mg辛伐他汀LDL－C达标率高于每日20mg氟伐他汀。结论 现行调脂治疗达标率较低,可能与选择药物的种类和药物剂量有关。     

小剂量普伐他汀与非诺贝特联合治疗混合型高血脂症临床疗效及安全性

目的探讨小剂量普伐他汀与非诺贝特联合应用治疗混合型高血脂症的临床疗效及安全性。方法混合型高血脂症患者189例,随机分为3组,即普伐他汀组(10mg/d,n=64)、非诺贝特组(200mg/d,n=63)、联合治疗组(普伐他汀10mg/d+非诺贝特200mg/d,n=62),治疗12周;12周时单药治疗血脂水平未全部达标者再随机分为3组,即联合治疗组、普伐他汀20mg治疗组及非诺贝特组,再治疗12周。观察治疗前后主要血脂水平的变化率、达标率及不良反应。结果(1)12周时联合治疗组血清总胆固醇(TC)、低密度脂蛋白胆固醇LDL-C、三酰甘油(TG)下降的幅度及血清高密度脂蛋白胆固醇(HDL-C)升高的幅度均高于单独用药组(P值均<0.01);TC、LDL-C、TG3项全部达标率也高于单独用药组(P均<0.01)。(2)单独用药血脂参数未全部达标者(n=35)改为联合治疗组治疗12周后TC及LDL-C下降的幅度与普伐他汀20mg组比较,差异无统计学意义,而降低TG及升高HDL-C幅度高于普伐他汀20mg组(P值均<0.01);联合治疗组与单用非诺贝特组比较,降低TC、LDL-C、TG及升高HDL-C的幅度高于非诺贝特组(P值<0.01或<0.05);联合用药组3项全部达标率为44%,而普伐他汀20mg组及非诺贝特组全部达标为21%、17%(P值均<0.01)。(3)联合治疗的不良反应与单独用药相比没有明显增加。结论小剂量普伐他汀(10mg/d)与非诺贝特(200mg/d)联合治疗混合型高血脂症,较单独用药更有效、更全面地改善各项血脂水平,具有良好的安全性和耐受性。     

国产与进口美百乐镇治疗高胆固醇血症效果比较

本文用随机双盲安慰剂对照临床试验方法，观察比较了国产美百乐镇（汕头陀滨制药厂）与进口美百乐镇（日本三共株式会社）治疗高胆固醇血症患者的效果。结果表明，国产和进口美百乐镇均可显著降低血清总胆固醇和低密度脂蛋白胆固醇水平，降总胆固醇个体疗效的总有效率分别达８８．６％、８８．７％；对血清甘油三酯也有轻度降低作用；对高密度脂蛋白胆固醇水平影响不大。副作用小，服用方便，有临床应用价值。     

普伐他汀早期治疗急性冠脉综合征疗效观察

目的探讨普伐他汀早期治疗急性冠脉综合征的临床效果。方法选取急性冠脉综合征患者120例,随机分为观察组和对照组各60例,对照组给予溶栓、抗凝、抗血小板、扩血管等常规药物治疗,观察组在常规药物治疗的基础上加用普伐他汀20mg,每晚睡前给药1次,8周后观察疗效及血脂水平。结果两组在显效率及总有效率方面比较,观察组高于对照组(P<0.01),观察组TC、LDL-C治疗后明显下降(P<0.01);对照组的TC、LDL-C治疗后无明显变化(P>0.05)。结论普伐他汀早期治疗急性冠脉综合征具有调脂,稳定粥样斑块的作用。     

Cholesterol lowering with statins: how WOSCOPS confounded the skeptics

The appearance of statins was key to our understanding of the pathologic effects of hypercholesterolemia. Before statins were available, physicians did not know whether cholesterol lowering improved cardiovascular health. Pioneering studies such as the Framingham Study and MR FIT identified high blood cholesterol as a risk factor for cardiovascular disease. However, because total cholesterol (TC) < or =300 mg/dL was common physicians were not convinced that this was abnormal. Cholesterol reduction by cholestyramine, nicotinic acid, and fibrates reduced the risk of coronary artery disease, but these treatments did not improve survival and quality of life. In 1987, the first statin arrived. This class of agents lowered cholesterol effectively with minimal side effects. Guidelines started to recognize the importance of cholesterol reduction. There followed a series of endpoint studies that emphatically demonstrated that statins improved cardiovascular outcomes. The WOSCOPS trial showed in a large cohort of men with TC >250 mg/dL and no prior MI that pravastatin dramatically reduced MI incidence, cardiovascular and total mortality, and revascularizations versus placebo over 5 years. WOSCOPS revealed for the first time that statin was effective for primary prevention. The benefits appeared early and persisted even after treatment ended. Statins also changed our perceptions with surprising ancillary effects.