Effects of atorvastatin on fasting and postprandial lipoprotein subclasses in coronary heart disease patients versus control subjects

The effects of atorvastatin at 20, 40, and 80 mg/day on plasma lipoprotein subclasses were examined in a randomized, placebo-controlled fashion over 24 weeks in 103 patients in the fasting state who had coronary heart disease (CHD) with low-density lipoprotein (LDL) cholesterol levels >130 mg/dl. The effects of placebo and atorvastatin 40 mg/day were examined in 88 subjects with CHD in the fasting state and 4 hours after a meal rich in saturated fat and cholesterol. These findings were compared with results in 88 age- and gender-matched control subjects. Treatment at the 20, 40, and 80 mg/day dose levels resulted in LDL cholesterol reductions of 38%, 46%, and 52% (all p <0.0001), triglyceride reductions of 22%, 26%, and 30% (all p <0.0001), and high-density lipoprotein (HDL) cholesterol increases of 6%, 5%, and 3%, respectively (all p <0.05 at the 20- and 40-mg doses). The lowest total cholesterol/HDL cholesterol ratio was observed with the 80 mg/day dose of atorvastatin (p <0.0001 vs placebo). Remnant-like particle (RLP) cholesterol decreased 33%, 34%, and 32%, respectively (all p <0.0001). Lipoprotein(a) [Lp(a)] cholesterol decreased 9%, 16%, and 21% (all p <0.0001), although Lp(a) mass increased 9%, 8%, and 10%, respectively (all p <0.01). In the fed state, atorvastatin 40 mg/day normalized direct LDL cholesterol (29% below controls), triglycerides (8% above controls), and RLP cholesterol (10% below controls), with similar reductions in the fasting state. At this same dose level, atorvastatin treatment resulted in 39%, 35%, and 59% decreases in fasting triglyceride in large, medium, and small very LDLs, as well as 45%, 33%, and 47% reductions in cholesterol in large, medium, and small LDL, respectively, as assessed by nuclear magnetic resonance (all significant, p <0.05), normalizing these particles versus controls (77 cases vs 77 controls). Moreover, cholesterol in large HDL was increased 37% (p <0.001) by this treatment. Our data indicate that atorvastatin treatment normalizes levels of all classes of triglyceride-rich lipoproteins and LDL in both the fasting and fed states in patients with CHD compared with control subjects.     

Effects of atorvastatin versus other statins on fasting and postprandial C-reactive protein and lipoprotein-associated phospholipase A2 in patients with coronary heart disease versus control subjects

The effects of atorvastatin (40 mg/day) versus placebo on fasting and postprandial plasma levels of high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were examined over 36 weeks in 84 patients who had coronary heart disease and low-density lipoprotein cholesterol levels >130 mg/dl and compared directly with the effects of fluvastatin, lovastatin, pravastatin, and simvastatin. Results were also compared with those obtained in age- and gender-matched control subjects (n = 84). Feeding increased median hs-CRP levels by 2% in patients (p = NS) and 22% in controls (p <0.01) and increased mean Lp-PLA2 values by 9% in patients (p = NS) but decreased values by 21% in controls (p <0.0001). Patients had 51% higher median hs-CRP values and 29% higher mean Lp-PLA2 values than did controls (p <0.05 for hs-CRP and Lp-PLA2) in the fasting state; however, Lp-PLA2 values were 62% higher (p <0.0001) in the fed state in patients compared with controls. Atorvastatin decreased median hs-CRP levels by 32% (p <0.01) and mean Lp-PLA2 values by 26% in patients (p <0.0001), with similar decreases in the fed state, and none of the other statins had any significant effect on these parameters. Change in Lp-PLA2 was significantly related to change in low-density lipoprotein cholesterol (p <0.01), with no significant relations with change in hs-CRP. Our data indicate greater differences in patients with coronary heart disease compared with controls in Lp-PLA2 in the fed state than in the fasting state and that atorvastatin is more effective than fluvastatin, lovastatin, pravastatin, or simvastatin for decreasing not only low-density lipoprotein cholesterol but also hs-CRP and Lp-PLA2.     

Comparison of fasting and postprandial plasma lipoproteins in subjects with and without coronary heart disease.

Plasma lipoprotein levels, including remnant-like particle (RLP) cholesterol and RLP triglycerides, were assessed in fasting (12 hours) and postprandial (PP) (4 hours after a fat-rich meal) states in 88 patients with coronary heart disease (CHD) and 88 controls. All lipoproteins were assessed by direct methods. We hypothesized that patients with CHD would have greater percent increases in their triglyceride levels, RLP cholesterol, and RLP triglycerides, in response to a fat-rich meal. In the fasting state, triglycerides, RLP cholesterol, RLP triglycerides, and low-density lipoprotein (LDL) cholesterol levels were all significantly higher in cases versus controls by 51%, 35%, 39%, and 40%, respectively. These levels were 57%, 37%, 64%, and 37% higher in the PP state, respectively. Mean high-density lipoprotein (HDL) cholesterol values were 27% lower in cases in both the fasting and PP states. After eating, triglycerides, RLP cholesterol, and RLP triglycerides increased 64%, 71%, and 290% in controls, respectively, whereas in cases these levels increased by 71%, 94%, and 340%, respectively (all p <0.0001). Percent increases in the PP state were not significantly different in cases versus controls. Following the fat-rich meal, LDL and HDL cholesterol decreased by 5% and 4% in controls, and by 7% and 6% in patients, with no significant difference in percent changes between groups. Fasting values correlated very highly with PP values for all parameters (all p <0.0001). Our data indicate that although patients with CHD have higher fasting and PP levels of triglycerides, RLP cholesterol, and RLP triglycerides than controls, the response (percent increase) to a fat-rich meal is comparable in both groups. Thus, a feeding challenge is not essential for assessment of these lipoproteins. Moreover, it is not necessary to obtain a fasting sample to assess direct LDL and HDL cholesterol.     

Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia

Although there is little information from primary or secondary prevention trials on cholesterol-lowering medication in diabetic patients, the reduction of elevated cholesterol is widely recommended for this group. The American Diabetes Association (ADA) recommends drug therapy in diabetic patients if low density lipoprotein (LDL)-cholesterol remains at > 130 mg/dl, or > 100 mg/dl in patients with macroangiopathy, after dietary intervention. When cholesterollowering medication is indicated, the choice of the drug must take into account the other lipid abnormalities that are often present and the need to maintain optimal glycaemic control. In the present study we compared the efficacy and safety of the novel HMG-CoA reductase inhibitor atorvastatin at the dose of 10 mg/day with simvastatin , lovastatin and pravastatin at doses of 10, 20 and 20 mg/day, respectively, and placebo, in type 2 diabetic patients with moderate elevation of LDL-cholesterol with or without elevation of triglycerides. All the quoted agents are enzyme inhibitors effective in lowering LDL-cholesterol in humans. The efficacy endpoints were the mean per cent changes in plasma LDL-cholesterol (primary), total cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol concentrations from baseline to the end of treatment (24 weeks). Atorvastatin at a dose of 10 mg/day produced: (1) a significant reduction in LDL-cholesterol (-37%) in comparison with equivalent doses of simvastatin (-26%), pravastatin (-23%), lovastatin (-21%), and placebo (-1%); (2) HDL-cholesterol increases (7.4%) comparable to or greater than those obtained with simvastatin (7.1%), pravastatin (3.2%), lovastatin (7.21%), and placebo (-0.5%); (3) a significantly greater reduction in total cholesterol (- 29%) than that obtained with simvastatin (-21%), pravastain (-16%), lovastatin (-18%), and placebo (1%); and (4) a significantly greater reduction in triglycerides than that obtained with all the other drugs and placebo. In all treatment groups no significant variation in fibrinogen concentration was observed. All reductase inhibitors studied had similar levels of tolerance. There were no incidents of persistent elevations of serum aminotransferases or myositis.     

Treating patients with documented atherosclerosis to national cholesterol education program-recommended low-density-lipoprotein cholesterol goals with atorvastatin,fluvastatin, lovastatin and simvastatin

Objectives. This study compared the efficacy and safety of atorvastatin, fluvastatin, lovastatin, and simvastatin in patients with documented atherosclerosis treated to U.S. National Cholesterol Education Program (NCEP) recommended low-density-lipoprotein (LDL) cholesterol concentration (≤100 mg/dl [2.59 mmol/liter]).Background. For patients with advanced atherosclerosis, NCEP recommends lipid-lowering drug therapy if LDL cholesterol remains ≥130 mg/dl (3.36 mmol/liter).Methods. A total of 318 men or women with documented atherosclerosis and LDL cholesterol ≥130 mg/dl (3.36 mmol/liter) and ≤250 mg/dl (6.5 mmol/liter), and triglycerides ≤400 mg/dl (4.5 mmol/liter) participated in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were titrated at 12-week intervals until the LDL cholesterol goal was reached. Number of patients reaching target LDL cholesterol levels and dose to reach target were evaluated.Results. At the starting doses, atorvastatin 10 mg produced significantly greater decreases (p < 0.05) in plasma LDL cholesterol than the other treatments. Subsequently, the percentage of patients reaching goal at the starting dose was 32% for atorvastatin, 1% for fluvastatin, 10% for lovastatin and 22% for simvastatin. Atorvastatin-treated patients required a lower median dose than other treatments. Median doses at week 54 with the last available visit carried forward were atorvastatin 20 mg/day, fluvastatin 40 mg/day + colestipol 20 g/day, lovastatin 80 mg/day, simvastatin 40 mg/day.Conclusions. A significantly greater number (p < 0.05) of patients with confirmed atherosclerosis treated with atorvastatin reached the target LDL cholesterol concentration at the starting dose than patients treated with fluvastatin or lovastatin, and significantly fewer (p < 0.05) patients treated with atorvastatin required combination therapy with colestipol to achieve target LDL cholesterol concentrations than all other statins tested.     

Effects of fasting and/or postprandial glucose on heart rate recovery in patients with coronary heart disease

AimThe impact of both fasting and postprandial glycaemia on heart rate recovery (HRR) has not been studied in patients with coronary heart disease (CHD). For this reason, we sought to determine the relationships between HRR and both fasting and postprandial glycaemia.MethodsA total of 4079 patients with baseline fasting plasma glucose (FPG) levels and 706 patients with 2-hour postprandial glucose (2hPG) levels were identified from the Coronary Artery Surgery Study registry, a database of 24,958 patients with suspected or proven CHD who had undergone cardiac catheterization between 1974 and 1979. Median long-term follow-up was 14.7 years (interquartile range: 9.8–16.2 years). The relationships between HRR and both FPG and 2hPG were studied.ResultsIn univariate analyses, increasing levels of both FPG and 2hPG were significantly associated with lower HRR. In multivariate models adjusted for age, exercise tolerance in METs, resting heart rate and maximum systolic blood pressure during exercise testing, FPG remained significantly associated with HRR while 2hPG did not.ConclusionBoth raised FPG and decreased HRR are independent predictors of total and cardiovascular (CV) mortality in subjects with CHD. Our data suggest that the mortality risk associated with elevated FPG may in part be due to deleterious effects on autonomic regulation of CV function, as reflected by lower HRR. Further studies are required to determine whether or not non-pharmacological and/or pharmacological treatments of increased fasting glucose have a beneficial influence on HRR.     

卡维地洛加普伐他汀对冠心病慢性心衰患者心功能改善的临床研究

目的 探讨卡维地洛加普伐他汀对冠心病慢性心力衰竭患者心功能的影响.方法 将183例冠心病心衰患者随机分为卡维地洛组（63例）、普伐他汀组（58例）和卡维地洛加普伐他汀联合用药组（62例）.三组均在常规抗心力衰竭治疗基础上分别加用一定剂量的上述药物,疗程12周,观察患者用药前后纽约心脏病学会（NYHA）心功能分级和血压、心率变化,采用超声心动图测定患者用药前后左心室舒张末期内径（LVEDD）、左心室收缩末期内径（LVESD）和左心室射血分数（LVEF）,治疗前后进行6 min步行试验（6-MWT）,采用酶联免疫法测定患者用药前后氨基末端脑钠肽前体（NT-proBNP）、心肌肌钙蛋白I（cTnI）水平变化,观察3个月内患者再住院率和心血管事件发生率.结果 治疗12周后,三组患者的LVEF、LVEDD、LVESD和血压、心率均得到明显改善（P＜0.05）;三组患者血浆中NT-proBNP与cTnI分子水平均明显下降（P＜0.05）,6-MWT提高明显（P＜0.05）.卡维地洛加普伐他汀组以上效果最明显,且再住院率和心血管事件发生率明显低于对照组（P＜0.05）.结论 卡维地洛加普伐他汀联合用药可以降低冠心病慢性心力衰竭患者的NT-proBNP和cTnI水平,改善心功能.     

The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease

Background: Although treatment of myocardial overload effectively reduces death from progression of heart failure, it is not known whether the retardation of progressive coronary artery disease obtained with lipid lowering treatment will prevent the onset and consequences of heart failure in patients without previous symptoms of heart failure.Methods and Results: In the Scandinavian Simvastatin Survival Study, 4444 patients with coronary heart disease without evidence of heart failure were randomized to placebo (n = 2223) or simvastatin 20–40 mg (n = 2221) and followed for more than 5 years. Among the patients who received placebo, 228 (10.3%) were diagnosed with heart failure during follow-up evaluation compared with 184 (8.3%) of patients who received simvastatin (P < .015). Mortality was 31.9% in the placebo group and 25.5% in the simvastatin group among patients who developed heart failure. These compare with 9.2 and 6.6%, respectively, among non-heart failure patients. There were 45 hospitalizations because of acute heart failure in the placebo group and 23 in the simvastatin group (NS). Patients who developed heart failure were more likely to have suffered a recurrent myocardial infarction and have a history of diabetes, peripheral artery disease, and hypertension than patients who did not develop congestive heart failure.Conclusion: Long-term prevention with simvastatin reduces the occurrence of heart failure in a cohort of patients with coronary heart disease without previous evidence of congestive heart failure.     

Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease

The efficacy and safety of atorvastatin 10 mg versus simvastatin 20 mg and atorvastatin 80 mg versus simvastatin 80 mg was determined in a 6-week, prospective, randomized, open-label, blinded end-point trial of dyslipidemic patients with and without coronary heart disease. A total of 1,732 patients with hypercholesterolemia and triglycerides < or =600 mg/dl (6.8 mmol/L) were randomized to receive either atorvastatin 10 mg (n = 650), simvastatin 20 mg (n = 650), atorvastatin 80 mg (n = 216), or simvastatin 80 mg (n = 216). The primary efficacy parameter was the change in low-density lipoprotein (LDL) cholesterol from baseline to week 6. Secondary efficacy parameters included the percent change from baseline to week 6 in total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein cholesterol, apolipoprotein B, and the percent of patients achieving their National Cholesterol Education Program (NCEP) LDL cholesterol goal at study end. Atorvastatin had significantly greater reductions from baseline in LDL cholesterol than simvastatin in both comparator groups: atorvastatin 10 mg (37.1%) versus simvastatin 20 mg (35.4%) (p = 0.0097), and atorvastatin 80 mg (53.4%) versus simvastatin 80 mg (46.7%) (p <0.0001). Atorvastatin 10 and 80 mg also provided significantly greater reductions in total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, and apolipoprotein B than simvastatin 20 and 80 mg, respectively (all p <0.05). All treatment groups had a significantly decreased LDL cholesterol/HDL cholesterol ratio from baseline (all p <0.0001). In both comparator groups a higher proportion of atorvastatin-treated patients reached their NCEP LDL cholesterol goal compared with simvastatin. All 4 study treatments were well tolerated.     

Early effects of simvastatin versus atorvastatin on oxidative stress and proinflammatory cytokines in hyperlipidemic subjects

The authors investigated the time-dependent action of atorvastatin and simvastatin on oxidative stress and cytokine levels immediately after the start of treatment. These factors play a role in endothelial dysfunction. Hyperlipidemic patients (n = 132) were assigned to treatment with 40 mg atorvastatin, 40 mg simvastatin, or placebo. Blood samples were taken before, 2 hours, 24 hours, 7 days, and 3 weeks after the administration of the statin or placebo to evaluate serum concentrations of total peroxides (TP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and soluble intercellular vascular adhesion molecule 1 (sICAM 1). In the atorvastatin group the TP changes were significantly different at 2 hours and 24 hours (p = 0.005), whereas in the simvastatin group there was a gradual, more or less linear decline in TP until 7 days (p = 0.006) and then a plateau. Simvastatin exhibited a faster statistically significant decrease over time in IL-6 and sICAM 1 levels (at 7 days, p = 0.014 and p = 0.001, respectively). TNF-alpha demonstrated a faster linear trend in the simvastatin group, but the significant effect appeared late (p = 0.006). Both simvastatin and atorvastatin exerted early beneficial effects on oxidative stress, proinflammatory cytokines, and endothelial activation in hyperlipidemic subjects. These effects became significant 2 hours following the initiation of therapy.     

Comparison of the efficacy and safety of rosuvastatin versus atorvastatin,simvastatin, and pravastatin across doses (STELLAR* Trial)

The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of low-density lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol > or =160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than pravastatin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were +7.7% to +9.6% compared with +2.1% to +6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments.     

他汀类药物对老年冠心病患者冠状动脉粥样硬化斑块的影响

目的评价他汀类药物对轻度胆固醇升高的老年冠心病患者冠状动脉粥样硬化斑块的影响。方法将LDL-C为2.6~3.6 mmol/L的57例冠心病患者分为>65岁组(Ⅰ组,30例)和≤65岁组(Ⅱ组,27例)。每例患者选取一处狭窄50%~70%的斑块为靶病变。分别于治疗前和治疗后12个月行冠状动脉造影(CAG)和靶病变的血管内超声(IVUS),比较血管、管腔和斑块体积,并观察斑块钙化情况。结果Ⅰ组和Ⅱ组患者12个月后LDL-C平均降至2.39 mmol/L和2.23 mmol/L,较基线下降32.1%和33.2%。两组患者血管、管腔和斑块体积在治疗前无显著差异。治疗12个月后,Ⅰ组血管、管腔和斑块体积无显著变化,Ⅱ组血管体积无变化;管腔体积由(68.8±14.4)mm3增加至(83.6±22.5)mm3(P<0.05),斑块体积由(80.1±18.6)mm3缩小至(69.9±21.7)mm3(P<0.05)。钙化斑块比例Ⅰ组明显高于Ⅱ组(56.7%vs25.9%,P<0.05)。结论他汀类药物可以阻止LDL-C轻度升高的老年冠心病患者冠状动脉斑块的进展。     

辛伐他汀和普伐他汀对冠心病sVCAM-1水平的影响

目的　探讨辛伐他汀和普伐他汀对冠心病 (CHD)患者血清中可溶性血管细胞粘附分子 1(sVCAM 1)水平的影响。　 方法　 10 6例CHD患者随机分为 3组 :A组 (安慰剂组 ) ,B组 (辛伐他汀组 ) ,C组 (普伐他汀组 )。采用酶联免疫吸附法 (ELISA)和常规酶法分别测定 3组患者用药前与用药 4、6周和 8周后血清sVCAM 1含量及总胆固醇 (TC)水平。　 结果 　①B组和C组患者服药 4、6周及 8周后血清sVCAM 1含量明显低于A组 (P <0 0 5 ,P <0 0 1,P <0 0 1)。②B组和C组患者服药 4、6周及 8周后血清sVCAM 1含量呈逐渐下降趋势 ,同用药前相比差异均有显著性 (P <0 0 5 ,P <0 0 1,P <0 0 1)。③B组和C组患者服药 4、6周及 8周后血浆TC含量与用药前相比差异均有统计学意义 (P <0 0 5 ,P <0 0 1,P <0 0 1)。④B组和C组患者血清sVCAM 1水平的降低与血浆TC含量的降低无明显相关性。　 结论 　辛伐他汀和普伐他汀不仅降低CHD患者血浆TC含量 ,而且降低血清中sV CAM 1的水平。     

阿托伐他汀与辛伐他汀治疗冠心病心绞痛的疗效与安全性比较

目的：比较阿托伐他汀与辛伐他汀治疗冠心病心绞痛的疗效及安全性。方法：选择冠心病慢性稳定型心绞痛患者150例,按数字表法被随机均分成阿托伐他汀组和辛伐他汀组。比较治疗前后两组间心绞痛发作次数、持续时间、疼痛程度、硝酸甘油用量差异及血脂变化,随访6个月,统计心血管事件发生率差异。结果：与治疗前比较,治疗12周后两组患者的心绞痛发作次数与硝酸甘油用量明显减少,每次持续时间缩短,疼痛程度明显减轻（P 均＜0.05）;但两组间治疗前及治疗后上述指标比较均无统计学差异（P均＞0.05）。与治疗前相比,治疗后阿托伐他汀组和辛伐他汀组患者的血清总胆固醇[（5.62±0.54）mmol/L比（3.68±0.41）mmol/L,（5.78±0.56）mmol/L比（3.33±0.43）mmol/L]、甘油三酯[（2.30±0.42）mmol/L比（1.62±0.34）mmol/L,（2.35±0.41）mmol/L比（1.68±0.69）mmol/L]、低密度脂蛋白胆固醇[（3.56±1.22）mmol/L比（2.76±0.83）mmol/L,（3.48±1.21）mmol/L比（2.43±0.72）mmol/L]显著下降,高密度脂蛋白胆固醇[（1.32±0.35）mmol/L比（1.58±0.34）mmol/L,（1.30±0.46）mmol/L比（1.60±0.45）mmol/L]水平则显著上升（P均＜0.05）,治疗后两组间血脂水平无明显差异（P＞0.05）;随访期间两组间心血管事件发生率无明显差异（28.00％比25.33％,P＞0.05）。结论：阿托伐他汀与辛伐他汀均能有效调节高血脂状态,治疗冠心病心绞痛疗效好,安全性高。     

Safety of lovastatin/extended release niacin compared with lovastatin alone, atorvastatin alone, pravastatin alone, and simvastatin alone (from the United States Food and Drug Administration adverse event reporting system)

Recent national guidelines support combination drug therapy targeting multiple lipid abnormalities. Current drug labeling warns of an increased risk of adverse events with statin and niacin combinations. These recommendations have been based solely on case reports. We compared the rates of adverse event reports (AERs) received by the United States Food and Drug Administration (1999 to March 2005) associated with the combination of lovastatin/niacin-extended release (ER) with those of lovastatin or niacin-ER alone, and other commonly used statins. The following AERs were considered: events that were fatal, life-threatening, or resulted in hospitalization (serious AERs), hepatotoxicity (liver AERs), and rhabdomyolysis (rhabdomyolysis AERs). We also calculated the prevalence of concomitant niacin-ER therapy in statin-associated AERs. The rate of serious AERs associated with the combination lovastatin/niacin-ER was similar to that of lovastatin or niacin-ER alone, and significantly less than that of atorvastatin or simvastatin. Likewise, the rates of liver and rhabdomyolysis AERs associated with lovastatin/niacin-ER were similar to those of the other statins or niacin-ER alone and lower than those of simvastatin-associated rhabdomyolysis reports (p <0.01). Concomitant niacin-ER use in statin-associated AERs was rare (相似文献   

辛伐他汀对冠心病患者血管内皮细胞功能障碍的治疗作用（英文）

目的：研究辛伐他汀对冠心病患者血管内皮细胞功能障碍的干预作用。方法：90例冠心病患者按LDL-C水平分为三组：辛伐他汀20mg组（37例,LDL-C≥2.5mmol/L）,辛伐他汀10mg组（35例,2.5mmol/L〉LDL-C≥1.8mmol/L）,常规治疗组（18例,LDL-C〈1.8mmol/L,未服辛伐他汀）,疗程均为8周。应用彩色多普勒超声诊断仪测量受试者肱动脉血流介导的舒张功能（FMD）。应用硝酸还原酶法检测受试者一氧化氮（NO）的含量。常规检测血清TC、TG、LDL-C及HDL-C的浓度。结果：8周后,与治疗前比较,辛伐他汀20mg,10mg组TC、TG和LDL-C浓度明显下降（P均〈0.05）,而HDL-C明显升高（P均〈0.05）;辛伐他汀20mg组与10mg组间各指标差异无显著性（P〉0.05）;与常规治疗组比较,辛伐他汀20mg、10 mg组FMD[（6.01±0.49）%比（9.01±0.39）%比（9.01±0.47）%]明显改善（P均〈0.01）、血清NO含量[（38.97±8.89）μmol/L比（47.67±10.89）μmol/L比（45.61±9.09）μmol/L]明显升高（P均〈0.05）,辛伐他汀20mg、10 mg组两组间NO和FMD亦无显著差异（P〉0.05）。结论：辛伐他汀可增加冠心病患者一氧化氮含量,改善血管内皮细胞功能,其作用机制与降低血清总胆固醇、甘油三酯和低密度脂蛋白可能有一定关系,但该作用无明显的量效关系,可能独立于降脂作用之外。     

他汀联合依折麦布与双倍剂量他汀对冠心病患者MACE影响的Meta分析

目的系统评价他汀联合依折麦布与双倍剂量他汀对冠心病患者主要不良心血管事件(MACE)的影响,为临床治疗提供参考。方法计算机检索The Cochrane Library、PubMed、Embase、CNKI、CSTJ、CBMdisc以及万方医学网,收集他汀联合依折麦布(联合组)对比双倍剂量他汀(他汀组)治疗冠心病患者的随机对照研究,提取相关资料并按照修改后的Jadad评分量表评价纳入研究质量,采用Rev Man 5.3软件进行Meta分析。结果共纳入29篇30项随机对照研究,合计4 757例患者。Meta分析结果显示,与他汀组比较,联合组MACE(P=0.03)、再发心绞痛(P0.001)和再发心肌梗死(P0.001)明显降低;而两组心源性死亡、血运重建、心力衰竭及卒中发生率差异无显著性。与他汀组比较,联合组转氨酶升高(P0.001)、肌酸激酶升高(P=0.02)和肌损伤发生率(P0.001)等显著降低。根据他汀种类和剂量进行亚组分析,结果显示,10 mg依折麦布+20 mg阿托伐他汀组降低MACE(P=0.02)、心肌梗死发生率(P=0.003)较阿托伐他汀40 mg组更具优势。随访时间长短对研究结果未见影响。结论对于冠心病患者,联合组治疗较他汀组在心绞痛、心肌梗死方面获益明显,心源性死亡和卒中方面差异无显著性,且不良反应发生率显著减少。     

Effects of atorvastatin on postprandial plasma lipoproteins in postinfarction patients with combined hyperlipidaemia

Enhanced and prolonged postprandial lipaemia is implicated in coronary and carotid artery disease. This study assessed the effects of atorvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on postprandial plasma concentrations of triglyceride-rich lipoproteins (TRLs). Sixteen middle-aged men with combined hyperlipidaemia (baseline low density lipoprotein (LDL) cholesterol and plasma triglyceride concentrations (median (interquartile range) of 4.54 (4.17-5.26)) and 2.66 (2.04-3.20) mmol/l, respectively) and previous myocardial infarction were randomised to atorvastatin 40 mg or placebo once daily for 8 weeks in a double-blind, cross-over design. The apolipoprotein (apo) B-48 and B-100 contents were determined in subfractions of TRLs as a measure of chylomicron remnant and very low density lipoprotein (VLDL) particle concentrations (expressed as mg apo B-48 or apo B-100 per litre of plasma), in the fasting state and after intake of a mixed meal. Atorvastatin treatment reduced significantly the fasting plasma concentrations of VLDL cholesterol, LDL cholesterol and VLDL triglycerides (median% change) by 29, 44 and 27%, respectively, and increased high density lipoprotein (HDL) cholesterol by 19%, compared with baseline. The postprandial plasma concentrations of large (Svedberg flotation rate (Sf) 60-400) and small (Sf 20-60) VLDLs and chylomicron remnants were almost halved compared with baseline (mean 0-6 h plasma concentrations were reduced by 48% for Sf 60-400 apo B-100, by 46% for Sf 60-400 apo B-48, by 46% for Sf 20-60 apo B-100 and by 27% for Sf 20-60 apo B-48), and the postprandial triglyceridaemia was reduced by 23% during active treatment. In conclusion, atorvastatin 40 mg once daily causes profound reductions of postprandial plasma concentrations of all TRLs in combined hyperlipidaemic patients with premature coronary artery disease.     

Beneficial effects of atorvastatin on sd LDL and LDL phenotype B in statin-naive patients and patients previously treated with simvastatin or pravastatin

BACKGROUND: The presence of increased levels of small dense (sd) LDL (phenotype B) is associated with a substantial increase of cardiovascular disease risk. Since lowering of plasma low-density lipoprotein-cholesterol (LDL-C) by statins involves an up-regulation of the LDL receptor, we questioned whether LDL lowering by atorvastatin affects different LDL subfractions equally. METHODS: Fifty-four hypercholesterolemic patients, requiring treatment for prevention of coronary heart disease received atorvastatin (10, 20 or 40 mg/day), either as initial therapy (n=33), or as replacement therapy (n=21) for pravastatin or simvastatin (both at 40 mg/day). In addition to plasma lipid measurements, cholesterol LDL subfractions were separated and analysed before and after 3 months of treatment. RESULTS: In addition to the expected LDL-C decrease (-34%; p<0.0001), a major reduction in sd LDL occurred after atorvastatin therapy (-38.2%; p<0.0001). Interestingly, sd LDL decreased as much in patients previously treated with other statins (-36%; p<0.002). A close correlation (r=0.89, p<0.001) was found between reduction of sd LDL and that of LDL-C, in patients with phenotype B. Although high-density lipoprotein-cholesterol (HDL-C) was not affected by atorvastatin treatment, plasma triglycerides decreased by 27.4% (p<0.0001). Only a weak correlation (r=0.35, p<0.01) was found between the reduction of plasma triglycerides and the decrease of sd LDL after atorvastatin treatment. CONCLUSION: These results show that the reduction of LDL-C by atorvastatin largely reflects a lowering of sd LDL. Our data also suggest that triglyceride lowering plays only a partial role in sd LDL reduction.