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PubMed2001

Effects of simvastatin treatment on sICAM-1 and sE-selectin levels in hypercholesterolemic subjects.

This study was performed to determine whether the levels of soluble intercellular adhesion molecule-1 (sICAM-l) and soluble endothelial molecule-1 (sE-selectin) were elevated in subjects with hypercholesterolemia who presented with no other risk factors or evidence of atherosclerosis. The effects of administration of an HMG-CoA reductase inhibitor on the serum levels of these molecules were also examined. Forty hypercholesterolemic subjects (HCh) (19 males and 21 females), without hypertension or cardiovascular disease, received placebo for 4 weeks. The patients were then randomized in two groups; 20 of them (simvastatin group) were treated with simvastatin (20 mg/day) and the other 20 (placebo group) continued placebo administration. After 12 and 24 weeks of either simvastatin or placebo treatment, sICAM-1 and sE-selectin levels were measured. The same parameters were measured in 20 control subjects (C) with normal cholesterol levels, matched for sex and age. HCh had sICAM-1 basal values higher than C (352.4+/-57.9 ng/ml versus 114.9+/-89.6 ng/ml; P<0.001); however, sE-selectin basal values were not different in the two groups. No correlation was observed between HCh sICAM-1 levels and cholesterol levels (total and low-density lipoprotein). Furthermore, cholesterol-lowering treatment with simvastatin did not significantly diminish sICAM-1 levels. Our findings would support the hypothesis that patients with isolated hypercholesterolemia and without clinical atherosclerosis may be silent carriers of arterial subendothelial inflammation, expressed as an increase of sICAM-1.

Adult↗
PubMed2001

C-reactive protein in patients with familial hypercholesterolemia: no effect of simvastatin therapy.

Patients with familial hypercholesterolemia (FH) are especially at risk for premature cardiovascular disease (CVD). Recent studies revealed C-reactive protein (CRP) as a strong predictor of future first or recurrent CVD events, suggesting that CRP plays an important role in the development of atherosclerosis. The aim of this study was to evaluate the effect of one year of simvastatin treatment on serum levels of CRP and to assess the influence of risk factors for CVD on CRP concentrations in patients with FH. We measured baseline CRP levels in 337 patients with FH. A second blood sample, collected after one year of treatment with simvastatin (20--40 mg once daily) was measured in a subgroup of 129 patients. Patients with CVD present at baseline had significantly higher serum levels of CRP (2.26 mg/l versus 1.55 mg/l, P<0.001). CRP levels were associated with smoking, body mass index, age, levels of triglycerides (TG), and the use of NSAIDs or anticoagulation drugs. Simvastatin therapy significantly improved lipid profiles in the intervention group. There was a small, but non-significant decrease of CRP levels upon treatment. CRP decreased from 1.51 mg/l median (interquartile range (IQR) 0.76--3.41) at baseline to 1.24 mg/l median (IQR 0.72--2.92) after treatment, (P=0.328). In conclusion, CRP levels were associated with the presence of CVD in FH patients. Simvastatin therapy had no significant effect on CRP levels in these patients.

Adolescent↗
PubMed2002

Simvastatin, an HMG-CoA reductase inhibitor, induces the synthesis and secretion of apolipoprotein AI in HepG2 cells and primary hamster hepatocytes.

Clinical studies have recently suggested that statin treatment may beneficially elevate plasma concentrations of high density lipoprotein (HDL)-cholesterol in patients with hyperlipidemia. Here, we have investigated the effect of a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on the synthesis and secretion of apolipoprotein AI (apoAI) in two model systems, HepG2 cells and primary hamster hepatocytes. Cultured cells were incubated with different doses of simvastatin (0.1-10 microM) for a period of 18 h. A dose-dependent increase in synthesis and secretion of apoAI was observed in both cell types. There was a significant increase in the synthesis of apoAI in HepG2 cells (44.3+/-12.1%), and hamster hepatocytes (212+/-2%) after treatment with 10 microM of the statin. The increase in apoAI synthesis appeared to result in a higher level of apoAI secreted into the culture media in both cell types (49.2+/-7.8% in HepG2, 197+/-0.2% in hamster hepatocytes). ApoAI mRNA levels were also significantly increased in both cell types in response to statin treatment. Control experiments with transferrin confirmed specificity of the effect on apoAI secretion. Analysis of a density fraction containing HDL particles in culture media revealed an increase in HDL-associated apoAI of 94.3+/-2.1% in HepG2 cells and 27.0+/-0.03% in hamster hepatocytes following 10 microM simvastatin-treatment. Comparative studies of simvastatin and lovastatin indicated a differential ability to induce apoAI synthesis and secretion, with simvastatin having a more significant effect. Thus, acute statin treatment of cultured hepatocytes (transformed as well as primary) resulted in a significant upregulation of apoAI mRNA and apoAI synthesis, causing oversecretion of apoAI and HDL extracellularly. The stimulatory effect on apoAI synthesis and secretion may thus explain the clinical observation of an elevated plasma HDL-cholesterol level in hyperlipidemic patients treated with certain statins.

Animals↗
PubMed2000

Simvastatin enhanced sodium nitroprusside-induced apoptosis of smooth muscle cells. An involvement of geranylgeraniol.

A decrease in serum cholesterol is one of the most beneficial effects in anti-atherogenesis. Nitric oxide is also an anti-atherogenic substance, inducing vasodilation and inhibits proliferation of smooth muscle cells (SMC). Therefore, we examined sodium nitroprusside (SNP)-induced apoptosis of vascular SMC with respect to cholesterol metabolism. Cultured vascular SMC from bovine carotid arteries and rat aorta were used. Apoptosis was determined by propidium iodide assay. Treatment of the SMC with SNP(100 micromol/l-1 mmol/l ) for 6 h induced a little nuclear fragmentation. SNP (1 mmol/l ) elicited apoptosis in 4.4+/-2.2% of cells. Pretreatment of SMC with simvastatin (1 microg/ml, 2 days), a hydroxymethylglutaryl Coenzyme A (HMG CoA) reductase inhibitor, synergistically enhanced SNP-induced apoptosis (% apoptosis =15. 9+/-3.3%). Either mevalonate (100 micromol/l) or geranylgeraniol (30 micromol/l) recovered the simvastatin (1 microg/ml)-enhanced SMC apoptosis induced by SNP. Neither squalene (10 mmol/l) nor farnesol (30 micromol/l) had a recovery effect on the simvastatin-enhanced SMC apoptosis induced by SNP. Pretreatment with simvastatin (1 microg/ml) reduced total cholesterol content in SMC. Mevalonate (100 micromol/l) restored a decrease in total cholesterol content. However, incubation with LDL deficient serum did not enhance SNP-induced apoptosis of SMC, although treatment with LDL deficient serum decreased the total cholesterol content in SMC. These data suggested that decrease in HMG CoA reductase metabolites, especially geranylgeraniol might enhance the SNP-induced apoptosis of SMC, and that, apoptosis was not involved in a decrease in cholesterol of SMC.

Animals↗
PubMed1988

Comparison between simvastatin and bezafibrate in effect on plasma lipoproteins and apolipoproteins in primary hypercholesterolaemia.

The ability of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, to lower lipid levels in 16 patients with primary hypercholesterolaemia was compared with that of bezafibrate in a 16-week, double-blind, parallel, placebo-controlled trial that was continued in an open crossover fashion. Simvastatin was better than bezafibrate at lowering total and low-density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations (30.4% [p less than 0.001], 37.3% [p less than 0.001], and 37.8% [p less than 0.001] vs 17.0%, 19.6%, and 24.0%, respectively). Both drugs increased the high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I, but this change was significant only with bezafibrate (p less than 0.05). Bezafibrate and simvastatin reduced triglycerides by 25.6% (p less than 0.001) and 13.7% (p less than 0.05), respectively. Very low-density lipoprotein (VLDL)-cholesterol was significantly reduced only by bezafibrate (44.3%, p less than 0.001). Both drugs were tolerated well and no serious side-effects were noted. The results show that simvastatin was more effective than bezafibrate in lowering total-cholesterol, LDL-cholesterol, and apolipoprotein B, while bezafibrate was better at lowering triglycerides and VLDL-cholesterol and at raising HDL-cholesterol and apolipoprotein A-I.

Adult↗
PubMed1999

Double-masked comparison of the quality of life of hypercholesterolemic men treated with simvastatin or pravastatin. International Quality of Life Multicenter Group.

The efficacy, safety, and impact on quality of life of once-daily treatment with simvastatin 20 mg and pravastatin 40 mg were compared in a multinational, randomized, double-masked trial involving 387 men 21 to 72 years of age with primary mild-to-moderate hypercholesterolemia. The trial consisted of a 12-week baseline period, which included 6 weeks of single-masked placebo administration, and a 12-week double-masked active treatment period. Throughout the trial, patients were maintained on a standard lipid-lowering diet. Efficacy variables were plasma lipid levels and a measurement of health-related quality of life evaluated by means of a self-administered questionnaire (the Nottingham Health Profile [NHP]) and other questionnaires related to general health, sexual function, and stress/life events. Clinic visits were scheduled at study entry (week -12), at initiation and week 5 of placebo (weeks -6 and -1, respectively); at randomization (week 1, day 1); and after 4, 8, and 12 weeks of active treatment. At each visit, blood samples were collected for determination of lipid levels and the NHP, the principal measure of health-related quality of life, was administered. Primary safety measures were adverse events and laboratory test results. All statistical comparisons were two-sided, and significance was defined as P< or =0.05 except for the NHP questionnaire, which was P< or =0.01. Treatment with simvastatin 20 mg/d for 12 weeks (n = 194) resulted in significantly greater reductions in plasma total cholesterol and low-density lipoprotein cholesterol levels (25.7% and 33.6%, respectively) compared with pravastatin 40 mg/d for 12 weeks (n = 193) (19.0% and 26.3%, respectively) (P<0.001). No detrimental effects on health-related quality-of-life measurements were reported with either drug. A small but statistically significant improvement in emotional reaction from baseline (P<0.001) was observed after 12 weeks of treatment with simvastatin. At least 75% of simvastatin-treated patients indicated no change in response from baseline on NHP domain scores; these findings were similar to those for pravastatin-treated patients. The differences in the changes in lipid profiles between the 2 treatment groups were not associated with any observed differences in tolerability or health-related quality-of-life measures.

Adult↗
PubMed2002

Dose-response effects of atorvastatin and simvastatin on high-density lipoprotein cholesterol in hypercholesterolaemic patients: a review of five comparative studies.

Epidemiological evidence and clinical trials with fibrate therapy show a clear relationship between low levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular risk. In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), the hydroxy-methylglutaryl-coenzyme A reductase inhibitors (statins), also raise the levels of HDL-C. This review summarizes the results of five randomized, multicenter studies in hypercholesterolaemic patients in which multiple doses of atorvastatin and simvastatin were compared for their effects on lipids and lipoproteins including HDL-C. Both statins reduced LDL cholesterol and achieved parallel decreases in TG, with atorvastatin showing a slight overall superiority in these studies. Both HDL-C and apolipoprotein (Apo) A-I, its associated apoprotein, were significantly and consistently increased by all doses of simvastatin. However, atorvastatin had a different dose-response effect from simvastatin on both lipid parameters. Whereas HDL-C and Apo A-I were elevated by low doses of atorvastatin, the effect diminished markedly with increasing dose suggesting a possible negative dose-response effect. At higher doses, simvastatin increased HDL-C and Apo A-I significantly more than atorvastatin. These data indicate that statins may not be identical in all their clinical properties relevant to reducing the risks of atherosclerosis.

Anticholesteremic Agents↗
PubMed2003

Leptin receptor polymorphism is associated with serum lipid levels and impairment of cholesterol lowering effect by simvastatin in Japanese men.

OBJECTIVE: To investigate whether leptin receptor (Ob-R) Arg223Gln polymorphism influences serum lipid levels and whether this polymorphism affects the efficiency of the cholesterol lowering HMG-CoA reductase inhibitor, simvastatin [Clin. Cardiol. 16 (1993) 317]. DESIGN: Case-control association study. SUBJECTS: We studied 201 Japanese men without medical care, and 78 Japanese who took simvastatin. METHODS: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum lipid and leptin levels were determined. RESULTS: Subjects with the Arg/Arg homozygotes had significantly higher serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels than those with the Arg/Gln heterozygotes and Gln/Gln homozygotes (TC: Arg/Arg: 213+/-3, Arg/Gln: 196+/-6, Gln/Gln: 184+/-5, P=0.004 for comparison among three genotypes, P=0.008 for difference between Arg/Arg and Arg/Gln, and P=0.025 for difference between Arg/Arg and Gln/Gln, LDL-C: Arg/Arg: 127+/-3, Arg/Gln: 112+/-6, Gln/Gln: 114+/-8, P=0.027) for comparison among three genotypes and P=0.011 for difference between Arg/Arg and Arg/Gln. Subjects with the Arg/Arg homozygotes had significantly lower serum high density lipoprotein cholesterol (HDL-C) levels than those with the Arg/Gln heterozygotes and Gln/Gln homozygotes (Arg/Arg: 55+/-1, Arg/Gln: 62+/-3, Gln/Gln: 57+/-7, P=0.046) for comparison among three genotypes and P=0.013 for difference between Arg/Arg and Arg/Gln. In addition, in 78 patients with hypercholesterolemia who took 5 mg simvastatin, the TC lowering effect by simvastatin in subjects with the Arg/Arg homozygotes was significantly lower than in those with the Arg/Gln heterozygotes and Gln/Gln homozygotes (the reduction in serum TC levels; 62+/-4 vs. 79+/-6, P=0.044). CONCLUSIONS: We demonstrate that Ob-R Arg223Gln polymorphism in Japanese men is associated with significant elevation of serum TC and LDL-C levels. Our data also show that the Arg/Arg homozygotes tend to show lowered level of serum HDL-C. Furthermore, this polymorphism tends to show an attenuated response to an HMG-CoA reductase inhibitor in terms of the cholesterol lowering effect. These results suggest that the Ob-R gene may serve as a novel modifier gene for hypercholesterolemia in Japanese men.

Adult↗
PubMed2002

Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering.

UNLABELLED: OBJECTIVES; This study was designed to assess the lipid-independent effects of simvastatin on myocardial perfusion (MP) and coronary microvascular permeability index (PI) at baseline and during episodes of increased cardiac demand in experimental hypercholesterolemia. BACKGROUND: Simvastatin preserves coronary endothelial function in experimental hypercholesterolemia independent of its lipid-lowering effect. However, the functional significance of this observation is unknown. METHODS: Pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC) and HC diet plus simvastatin (HC+S) for 12 weeks. Subsequently, cardiac electron beam computed tomography was performed before and during intravenous infusion of adenosine and dobutamine, and MP and PI were calculated. RESULTS: Total and low density lipoprotein cholesterol levels were similarly and significantly increased in HC and HC+S animals compared with N. Basal MP was similar in all groups. Myocardial perfusion significantly increased in response to either adenosine or dobutamine in N and HC+S animals. Dobutamine also significantly increased MP in HC animals. However, the changes of MP in response to either drug were significantly lower in the HC group compared with the other two groups (p < 0.01 for adenosine and p < 0.05 for dobutamine vs. N and HC+S). Basal PI was similar in all groups and was not altered by either drug in N and HC+S animals. In contrast, PI significantly increased in HC pigs during infusion of either adenosine (p < 0.001) or dobutamine (p < 0.05). CONCLUSIONS: These findings demonstrate that chronic administration of simvastatin preserves myocardial perfusion response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia independent of lipid lowering.

Animals↗
PubMed1998

Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men.

OBJECTIVES: The aim of this study was to determine whether the combination of lipid-lowering therapy and vitamin E supplementation improves peripheral endothelial function and whether it is more effective than lipid-lowering therapy alone. BACKGROUND: Endothelium-dependent vasodilation is impaired in coronary and peripheral arteries of patients with hypercholesterolemia. Coronary endothelial function has been shown to improve under lipid-lowering and antioxidant therapy, but the effect of additive vitamin E supplementation in the brachial artery is unknown. METHODS: Seven patients with hypercholesterolemia (mean+/-SD; age 51+/-10 yr) were studied. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation (NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline (BL I), 2) after 8 weeks of simvastatin (20 mg) and vitamin E (300 IU) therapy (Comb I), 3) after withdrawal of vitamin E for 4 weeks (Statin), 4) after therapy as in #2 for 4 weeks (Comb II) and 5) after withdrawal of both drugs for 4 weeks (BL II). RESULTS: Combined simvastatin and vitamin E therapy reduced total cholesterol (Comb I vs. BL I: 276+/-22 vs. 190+/-14 mg/dl, p < 0.0001) and low-density lipoprotein (LDL)-C (197+/-22 vs. 106+/-22 mg/dl, p < 0.00001), augmented alpha tocopherol levels normalized to LDL (12.2+/-4.1 vs. 4.9+/-0.9 microg alpha-T/100 mg% LDL-C, p < 0.01) and resulted in significant improvements in FMD (16.4+/-4.7 vs. 4.9+/-2.5%, p < 0.001) as well as NMD (17.9+/-4.3 vs. 11.2+/-2.8%, p < 0.01). The ratio of FMD to NMD (0.92+/-0.17 vs. 0.46+/-0.24%, p < 0.05) also increased under combination therapy, indicating a greater improvement of FMD than that of NMD. After withdrawal of vitamin E, both FMD (Comb I vs. Statin: 16.4+/-4.7 vs. 7.9+/-4.7%, p < 0.01) and NMD (17.9+/-4.3 vs. 10.9+/-4.5%, p < 0.05) decreased significantly such that simvastatin alone only tended to improve FMD and did not change NMD. Results under combination therapy (Comb II vs. BL II) were reproducible. CONCLUSIONS: Combined vitamin E and simvastatin therapy leads to an improvement of FMD and NMD in the brachial artery of patients with hypercholesterolemia. The improvement of FMD is more pronounced after combination therapy than after lipid-lowering therapy alone, similar to previous findings in the coronary circulation.

Adult↗
PubMed1993

Simvastatin inhibits PDGF-induced DNA synthesis in human glomerular mesangial cells.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A-(HMGCoA) reductase ameliorate glomerular pathology and renal dysfunction in different models of glomerular disease. This effect has generally been attributed to a decrease in the circulating levels of cholesterol. Focal or diffuse mesangial cell proliferation is a common feature of glomerular pathology. There is now evidence from studies in vitro and in vivo that platelet-derived growth factor (PDGF) is an important mediator of glomerular hypercellularity. The activity of HMGCoA reductase has previously been shown to be a requirement for cell growth. In the present study, we examined the effect of simvastatin, and HMGCoA reductase inhibitor, on PDGF-induced DNA synthesis and PDGF B chain gene expression in human glomerular mesangial cells. In addition, we investigated the effect of simvastatin on phospholipase C (PLC) and protein kinase C (PKC) activation stimulated by PDGF. We demonstrate that treatment of the cells with simvastatin completely inhibits PDGF-induced DNA synthesis. This inhibition is reversed by mevalonate but not by cholesterol or farnesol, two major metabolites of the mevalonate pathway. On the other hand inhibition of HMGCoA reductase does not influence PDGF-induced activation of PLC and PKC, or PDGF B chain gene expression. These data suggest that simvastatin acts at a late step in the PDGF mitogenic pathway without interfering with other early cellular responses elicited by this growth factor. These studies also raise the possibility that the ameliorative effect of HMGCoA reductase inhibitors on glomerular pathology may be mediated, at least in part, by a direct cellular effect.

Cells, Cultured↗
PubMed2005

Beneficial effect of simvastatin and pravastatin treatment on adverse cardiac remodelling and glomeruli loss in spontaneously hypertensive rats.

The aim of the present study was to investigate the possibility of different effects of the hydrophobic statin simvastatin and the hydrophilic statin pravastatin on the remodelling process in the overloaded left ventricle and renal cortex of SHRs (spontaneously hypertensive rats). Fifteen SHRs were treated for 40 days with simvastatin, pravastatin or placebo (water) via orogastric administration. Left ventricle and renal cortex were examined by light microscopy and stereology. LV (left ventricular) cardiomyocyte nuclei (N[cmn]) and glomeruli (N[gl]) numbers were estimated by the dissector method. BP (blood pressure) and serum triacylglycerols (triglycerides) were lower in the statin-treated groups than in the untreated control group. The volume density of the interstitial connective tissue was smaller and length density of the intramyocardial arteries, as well as the arteries/cardiomyocyte ratio, was greater in the statin-treated groups than in the control group. No difference was observed between the two statin-treated groups. The cross-sectional cardiomyocyte area was significantly smaller in the simvastatin-treated group than in the control or pravastatin-treated groups, and it was smaller in the pravastatin-treated group than in the control group. N[cmn] and N[gl] were greater in the two statin-treated groups than in the control group, but no significant difference was observed between the two statin-treated groups. In conclusion, administration of the statins simvastatin and pravastatin to SHRs effectively prevented the elevation in BP and serum triaclyglycerols, and also attenuated adverse cardiac and kidney remodelling by preventing LV hypertrophy, enhancing myocardial vascularization with the decrease in interstitial fibrosis and attenuating cardiomyocyte and glomerular loss.

Animals↗
PubMed1999

A comparison of the use, effectiveness and safety of bezafibrate, gemfibrozil and simvastatin in normal clinical practice using the New Zealand Intensive Medicines Monitoring Programme (IMMP).

AIMS: Because of the importance of treating dyslipidaemia in the prevention of ischaemic heart disease and because patient selection criteria and outcomes in clinical trials do not necessarily reflect what happens in normal clinical practice, we compared outcomes from bezafibrate, gemfibrozil and simvastatin therapy under conditions of normal use. METHODS: A random sample of 200 patients was selected from the New Zealand Intensive Medicines Monitoring Programme's (IMMP) patient cohorts for each drug. Questionnaires sent to prescribers requested information on indications, risk factors for ischaemic heart disease, lipid profiles with changes during treatment and reasons for stopping therapy. RESULTS: 80% of prescribers replied and 83% of these contained useful information. The three groups were similar for age, sex and geographical region, but significantly more patients on bezafibrate had diabetes and/or hypertension than those on gemfibrozil or simvastatin. After treatment and taking the initial measure into account, the changes in serum lipid values were consistent with those generally observed, but with gemfibrozil being significantly less effective than expected. More patients (15.8%S) stopped gemfibrozil because of an inadequate response compared with bezafibrate (5.4%) and simvastatin (1.6%). Gemfibrozil treatment was also withdrawn significantly more frequently due to a possible adverse reaction compared with the other two drugs. CONCLUSIONS: In normal clinical practice in New Zealand gemfibrozil appears less effective and more frequently causes adverse effects leading to withdrawal of treatment than either bezafibrate or simvastatin.

Bezafibrate↗
PubMed1996

Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil.

The occurrence of rhabdomyolysis is one of the rare side-effects of the cholesterol-lowering agent simvastatin. During the use of lovastatin, an agent related to simvastatin, the risk of this side-effect might be increased when cyclosporin or gemfibrozil are used concomitantly. It is possible that this also applies for simvastatin. We present two patients who developed rhabdomyolysis during the concomitant use of simvastatin and gemfibrozil.

Drug Synergism↗
PubMed1998

Effects of Simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia.

OBJECTIVES: Patients with combined hyperlipidemia are at increased risk for development of coronary heart disease. The purpose of this study was to evaluate the efficiency and the safety of treatment with Simvastatin and omega-3 fatty acids in patients with this lipid disorder. DESIGN: A double-blind placebo controlled, randomized study evaluating the effects of Simvastatin separately and in combination with omega-3 fatty acids in 41 healthy patients with defined hyperlipidemia. After a 16 weeks dietary run-in period the patients were treated in periods of 5 weeks. RESULTS: As expected Simvastatin (20 mg day[-1]) reduced serum total cholesterol, triacylglycerols, apolipoproteins B and E and increased HDL-cholesterol and apolipoprotein A1. Addition of omega-3 fatty acids (4 g day[-1]) further decreased serum triacylglycerols (P = 0.007), total cholesterol (P = 0.052) and apolipoprotein E (P = 0.035). No significant changes attributable to supplementation of polyunsaturated fatty acids on the content of lipid peroxides in plasma and in the various lipoprotein fractions were observed. CONCLUSIONS: The combined treatment of Simvastatin and omega-3 fatty acids seems to be an efficient and safe alternative for patients with combined hyperlipidemia.

Adult↗
PubMed1999

Atorvastatin compared with simvastatin in patients with severe LDL hypercholesterolaemia treated by regular LDL apheresis.

OBJECTIVES: Atorvastatin is a new potent HMG-CoA reductase inhibitor. We evaluated whether patients with coronary heart disease and severe hypercholesterolaemia showing insufficient LDL (low-density lipoprotein) cholesterol reduction despite combined therapy with simvastatin and regular LDL apheresis will benefit from atorvastatin therapy. SETTING: Tertiary care centre, university hospital. METHODS: In 21 patients treated by LDL apheresis, concomitant simvastatin therapy (40 mg day-1) was replaced by atorvastatin (40 mg day-1) and increased to 60 and 80 mg day-1 (each for 3 months) if no side-effects were reported and NCEP treatment goals were not reached. RESULTS: In 20 of 21 patients (95%), atorvastatin resulted in significant reduction of LDL cholesterol compared with simvastatin (by 10%, additional 8% and additional 1%, with 40, 60 and 80 mg day-1, respectively). In four patients, NCEP treatment goals were reached (in three by atorvastatin alone, and in one by atorvastatin and apheresis). Patients with little reduction in LDL cholesterol to 40 mg day-1 atorvastatin benefited most by increasing the dose to 60 mg day-1 (additional 13% reduction), whilst those responding to atorvastatin 40 mg day-1 benefited less (additional 1.9% reduction). During atorvastatin therapy, significantly less plasma had to be treated during apheresis resulting in shorter apheresis time. Eight patients (38%) reported side-effects, resulting in discontinuation of atorvastatin in three (14%) and dose reduction in five patients (24%), whilst no elevation of biochemical markers was observed. CONCLUSION: Concomitant atorvastatin therapy is superior to simvastatin therapy in patients with severe hypercholesterolaemia treated with regular LDL apheresis, but is associated with a high rate of subjective side-effects.

Anticholesteremic Agents↗
PubMed2002

Effects of simvastatin and atorvastatin on inflammation markers in plasma.

OBJECTIVES: To study the effect of statins on plasma markers for inflammation. DESIGN: Patients with hypercholesterolemia were randomized in one of the following treatments: Simvastatin (S) + placebo: S 40 mg for 6 weeks - S 80 mg for 6 weeks - S 80 mg for 24 weeks and Atorvastatin (A) + placebo: A 20 mg for 6 weeks - A 40 mg for 6 weeks - A 80 mg for 24 weeks. SUBJECTS: Forty-seven patients with hypercholesterolemia were recruited in four different outpatient clinics. MAIN OUTCOME MEASURES: Samples were obtained at randomization after 6, 12 and 36 weeks. Plasma or serum was analysed for lipids and for inflammation markers: C-reactive protein (CRP), serum amyloid A (SAA), soluble phospholipase A2 (SPLA2), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6). RESULTS: The reduction in LDL was similar for the two statins, except at the highest dose of atorvastatin (41 vs. 47%). The increase in HDL tended to be more pronounced in the simvastatin group, significantly so on the highest dose of atorvastatin (P < 0.05). CRP and SAA was significantly reduced by atorvastatin, whilst no reduction was seen for simvastatin. There was a significant difference in treatment effects between the two statins. Both statins caused a reduction in SPLA2. For IL-6 and ICAM-1 only small and inconsistent reductions were observed for both statins. CONCLUSION: Atorvastatin reduced the liver-derived acute-phase reactants, CRP and SAA, whilst the effect of simvastatin was small or absent. Small and inconsistent effects were seen for both statins on plasma levels of IL-6 and ICAM-1.

Adult↗
PubMed2000

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.

Aged↗