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PubMed2001

Effect of simvastatin alone and in combination with cytosine arabinoside on the proliferation of myeloid leukemia cell lines.

BACKGROUND: Cholesterol biosynthesis is regulated by the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol and its derivatives are required in high concentrations by neoplastic proliferating cells for both DNA synthesis and cell growth. Thus, inhibition of HMG-CoA reductase could effect cell cycle progression and proliferation. Therefore, we examined the effect of an HMG-CoA reductase inhibitor (simvastatin) alone and in combination with cytosine arabinoside (ARA-C) on the proliferation of two AML cell lines. METHODS: AML blasts derived from two cell lines (HL-60 and AML-2) were incubated with increasing concentrations of either simvastatin alone or simvastatin alone for 24 hours with ARA-C added thereafter. The effect of the drugs on cell proliferation in liquid culture (3H thymidine uptake) and on clonogenic assay was analyzed. RESULTS: We found that the number of proliferating AML blasts (suspension cultures) and colony formations (agar cultures) of both cell lines declined significantly after incubation with simvastatin. Preincubation of both cell lines with simvastatin by the addition of increasing concentrations of ARA-C produced a degree of growth inhibition that was significantly greater than that of the individual compounds. This antigrowth interaction was additive rather than synergistic. CONCLUSIONS: We conclude that simvastatin has a major antiproliferative effect on AML blasts in vitro. Also, the combination of simvastatin and ARA-C significantly enhanced the antiproliferative effect of each drug. These findings may open new avenues in both the laboratory and clinical research of the treatment of leukemia.

Anticholesteremic Agents↗
PubMed1998

Treatment of hypercholesterolemia and combined hyperlipidemia with simvastatin and gemfibrozil in patients with NIDDM. A multicenter comparison study.

OBJECTIVE: To compare the lipid-lowering efficacies of simvastatin and gemfibrozil in NIDDM patients with combined (mixed) hyperlipidemia (CHL) or isolated hypercholesterolemia (IHC). RESEARCH DESIGN AND METHODS: Patients with primary dyslipidemia and NIDDM were recruited for this double-blind, double-dummy comparison study from 10 Finnish centers. After a 4-week placebo run-in period, they were randomly assigned to simvastatin or gemfibrozil. The simvastatin group (n = 47) received 10 mg once nightly for 8 weeks, 20 mg for the next 8 weeks, and 40 mg for the third 8-week period. The gemfibrozil group (n = 49) received 600 mg twice daily throughout the 24 weeks. The lipid-lowering efficacies of both drugs were compared in all patients as well as separately in patients with CHL and IHC. RESULTS: In all patients, simvastatin reduced LDL and total cholesterol and the LDL-to-HDL cholesterol ratio more effectively, whereas gemfibrozil was more effective in elevating HDL cholesterol and decreasing triglyceride levels. The drug effects differed according to lipid phenotype at baseline. Simvastatin decreased LDL cholesterol levels by 30-40% in both phenotypes. Gemfibrozil caused a 15% reduction in LDL cholesterol in IHC but no change in CHL patients. Simvastatin produced 15-30% reductions in triglyceride levels in CHL but no change in IHC patients. Gemfibrozil caused reductions in triglycerides in CHL (50% and more) and in IHC (40%) patients, with 12-18% increases in HDL cholesterol in these groups. CONCLUSIONS: Simvastatin is useful in both CHL and IHC patients, whereas gemfibrozil can be used in patients with high triglyceride and low or normal LDL cholesterol levels.

Anticholesteremic Agents↗
PubMed2004

Role of simvastatin as an immunomodulator in type 2 diabetes.

OBJECTIVE: To test the hypothesis that simvastatin reduces the levels of circulating immune complexes (ICs) containing modified lipoproteins (mLDLs; mLDL-ICs), which may represent an additional mechanism for the reduced incidence of cardiovascular events in patients treated with simvastatin. RESEARCH DESIGN AND METHODS: A total of 26 patients with type 2 diabetes and triglyceride levels <400 mg/dl who were not receiving lipid-lowering medications or CYP 3A4 inhibitors were enrolled in the study. After 2 weeks on a lipid-lowering diet and exercise, the patients were started on simvastatin 20 mg/day. The dose of simvastatin was adjusted until the levels of LDL cholesterol were < or =100 mg/dl. Blood was collected at baseline, 3 and 6 months after LDL cholesterol levels reached target, and 3 months after stopping simvastatin to measure advanced glycation end product LDL and oxidized LDL antibodies, mLDL-IC, intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin, metalloproteinase-1 (MMP-1), lipid profile, liver function tests, creatinine kinase, glucose, and HbA(1c). RESULTS: Twenty-one patients completed the study. Their HbA(1c) remained within 1% of baseline levels. There was a highly significant decrease in mLDL-IC levels after 3 and 6 months of treatment with simvastatin, with a return to near baseline levels after discontinuation. CONCLUSIONS: Simvastatin significantly reduced the concentration of mLDL-IC, probably as a consequence of both a decrease in the formation of mLDL and to a reduction in the titers of mLDL antibodies. This effect is likely to have a beneficial impact in the inflammatory reaction associated with atherosclerosis.

Adjuvants, Immunologic↗
PubMed2005

The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells.

Statins have been postulated to affect the bone metabolism. Recent experimental and epidemiologic studies have suggested that statins may also have bone protective effects. This study assessed the effects of simvastatin on the proliferation and differentiation of human bone marrow stromal cells (BMSCs) in an ex vivo culture. The bone marrow was obtained from healthy donors. Mononuclear cells were isolated and cultured to osteoblastic lineage. In the primary culture, 10(-6) M simvastatin diminished the mean size of the colony forming units-fibroblastic (CFU-Fs) and enhanced matrix calcification. At near confluence, the cells were sub-cultured. Thereafter, the alkaline phosphatase (ALP) activities of each group were measured by the time course of the secondary culture. Simvastatin increased the ALP activity in a dose dependent manner, and this stimulatory effect was more evident during the early period of culture. A 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was performed during the secondary culture in order to estimate the effect of simvastatin on the proliferation of human BMSCs. When compared to the control group, simvastatin significantly decreased the proliferation of cells of each culture well. 10(-6) M of simvastatin also significantly enhanced the osteocalcin mRNA expression level. This study shows that simvastatin has a stimulatory effect on bone formation through osteoblastic differentiation, and has an inhibitory effect on the proliferative potential of human BMSCs.

Alkaline Phosphatase↗
PubMed1999

International multicentre comparison of cerivastatin with placebo and simvastatin for the treatment of patients with primary hypercholesterolaemia. International Cerivastatin Study Group.

An international multicentre double-blind randomised trial compared the efficacy and safety of cerivastatin (0.025, 0.05, 0.1 and 0.2 mg once daily) with placebo and simvastatin (20 mg) over a period of 12 weeks, with study extensions to 52 and 100 weeks. The primary efficacy parameter was the percentage change in low density lipoprotein cholesterol (LDL-C). This was reduced from the baseline by 12.5% (0.025 mg) to 30.6% (0.2 mg) compared with falls of 2.0% on placebo and 40.3% on simvastatin. All four cerivastatin doses and simvastatin (20 mg) produced significantly greater falls than placebo (p < 0.0001) and the decrease in LDL-C was dose-dependent for cerivastatin. Simvastatin produced significantly greater falls than any cerivastatin dose or placebo (p < 0.0001). The effect was maintained at 1 year but somewhat attenuated at 100 weeks. Significant falls were also seen in serum total cholesterol and triglycerides. High density lipoprotein cholesterol (HDL-C) levels were significantly increased by cerivastatin (0.1 and 0.2 mg) and simvastatin (20 mg) at 12 weeks and increased further by 100 weeks. Mean fasting apolipoprotein A1 and lipoprotein A1 were increased and apolipoprotein B decreased by cerivastatin and simvastatin therapy. All doses of cerivastatin produced significant falls in the total cholesterol/HDL-C ratio at 12 weeks (0.5-1.6) compared with a fall of 2.1 for simvastatin (20 mg). Cerivastatin was well tolerated. Elevations in creatine phosphokinase, aspartate aminotransferase and alanine aminotransferase were mostly minor and transitory. Vital signs, electrocardiogram determinations, urinalysis and ophthalmic assessment showed similar results for both drugs. Cerivastatin, at doses of 0.1 mg and 0.2 mg daily, is considered to be of therapeutic value in the treatment of patients with primary hypercholesterolaemia, with 0.2 mg cerivastatin achieving reductions of LDL-C and total cholesterol similar to those achieved in the WOSCOP and CARE studies.

Anticholesteremic Agents↗
PubMed2002

[Effect of simvastatin on bone morphogenetic protein-2 expression and alkaline phosphatase activity of bone marrow stromal cell].

OBJECTIVE: To study the effect of simvastatin on the expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphates (ALP) activity in the primary cultured bone marrow stromal cells, and to elucidate the mechanism of the anabolic osteogenetic effect of simvastatin. METHODS: Bone marrow stromal cells in femur and tibia of adult mouse were cultured in vitro. after treated with different concentrations of simvastatin (0, 0.1, 0.2, 0.5 and 1.0 mumol/L) or recombinant human BMP-2 for 72 hours, ALP activity of bone marrow stromal cells was determined. BMP-2 expression of bone marrow stromal cells was analyzed by using immunocytochemistry and Western blotting. RESULTS: After treated with simvastatin for 72 hours, BMP-2 expression increased, while little BMP-2 expression could be observed in the control group. ALP activity also increased in a dose-dependent manner; t-test showed that ALP activity in the group which concentrations of simvastatin were 0.5 mumol/L (t = 2.35, P = 0.041), 1.0 mumol/L (t = 2.348, P = 0.041) had significant difference when compared with control group. CONCLUSION: Simvastatin lead to high expression of BMP-2 in bone marrow stromal cells, via the increased auto- or para-crine of BMP-2, and ALP activity increased. These may be parts of the mechanism on the anabolic osteogenetic effect of simvastatin.

Alkaline Phosphatase↗
PubMed2000

[Determination of simvastatin in human plasma by high performance liquid chromatography].

Simvastatin is widely used in the treatment of hypercholestero-lemia. Recently, it was reported that it is also effective in reducing lethality in coronary heart disease. A simple and sensitive reversed-phase liquid chromatographic method has been developed and validated for the analysis of simvastatin in human plasma. Simvastatin and internal standard lovastatin in plasma were extracted with cyclohexane-dichloromethane (3.5:1, V/V), and then measured by HPLC using a Lichrospher C18 column as stationary phase and an acetonitrile-water (70:30, V/V) mixture as mobile phase. The flow rate was 1.2 mL/min. Simvastatin was quantified by UV at 237 nm. The calibration curve showed a good linearity in the mass concentration range of 0.25-50.0 micrograms/L. The regression equation is: Y = 0.0364 rho + 0.00583, r = 0.9998. Intra-day and inter-day coefficients of variation of assay for simvastatin in plasma < 7.94% and < 8.58%, respectively. The recoveries of simvastatin were > 93.3%. The method has been used to determine simvastatin in plasma from 12 healthy male volunteers.

Adult↗
PubMed2004

Simvastatin treatment restores vasoconstriction and the inhibitory effect of LPC on endothelial relaxation via affecting oxidizing metabolism in diabetic rats.

Oxidative stress and dyslipidaemia play an important role in the development of diabetes-induced vascular complications. The aim of this study was to examine the reversal effects of simvastatin on some metabolic and oxidative parameters, and vascular functions in diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.). Eight weeks after STZ induction, some of the diabetic and control rats were treated with simvastatin (10 mg/kg rat/d) for 4 weeks. Plasma glucose, triglyceride and total cholesterol concentrations were significantly increased in 12-week diabetic rats. Simvastatin treatment stopped the loss of body weight, completely normalized the increase of plasma lipids and partially reduced the hyperglycaemia in diabetic rats. Increased malondialdehyde levels, catalase and glutathione peroxidase activities were normalised by simvastatin treatment in diabetic aorta. Phenylephrine (PE)-induced contractility in aorta rings was unaffected by diabetes, but was markedly decreased after simvastatin treatment in both control and diabetic rats. Reduction of endothelium-dependent vasorelaxation in diabetes was significantly ameliorated by simvastatin treatment. Incubation of aorta rings with lysophosphatidylcholine, a component of the oxidized LDL, did not significantly affect PE-induced contractions, but reduced endothelium-dependent relaxations more in untreated-diabetic rats than in other experimental groups. The endothelium-independent vasorelaxations were similar in all ring preparations. These results indicate that simvastatin treatment may ameliorate diabetes-induced abnormal vasoconstriction and endothelial dysfunction via affecting general and oxidizing metabolism, nitric oxide disability and intracellular calcium mobilisation.

Animals↗
PubMed2006

Simvastatin inhibits production of interleukin 6 (IL-6) and IL-8 and cell proliferation induced by tumor necrosis factor-alpha in fibroblast-like synoviocytes from patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the synovial environment is characterized by intense immunological activity. Evidence suggests that statins modulate immune functions and may have a beneficial effect on patients with RA. We investigated whether simvastatin could inhibit the expression of interleukin 6 (IL-6) and IL-8 and cell proliferation induced by tumor necrosis factor-alpha (TNF-alpha) in fibroblast-like synoviocytes (FLS) obtained from RA patients undergoing joint replacement therapy. METHODS: RA FLS were cultured with or without 0.05-10 microM simvastatin for 12 h. Cytokine mRNA expression and secretion levels were detected using real-time PCR and ELISA, respectively. Cell proliferation of FLS induced by TNF-alpha was determined by MTT assay. RESULTS: Real-time PCR analysis revealed that the levels of IL-6 and IL-8 mRNA expressed by FLS were reduced by simvastatin in a dose-dependent manner. Levels of IL-6 and IL-8 in FLS culture supernatants were decreased by simvastatin in a time-dependent and dose-dependent manner. MTT assay revealed that simvastatin could inhibit proliferation of FLS induced by TNF-alpha. These effects of simvastatin on IL-6 and IL-8 production and cell proliferation were reversed in the presence of mevalonic acid or geranylgeranyl-pyrophosphate, but not with farnesyl-pyrophosphate. CONCLUSION: Our results suggest that the beneficial effect of simvastatin in RA patients may involve inhibition of IL-6 and IL-8 production, as well as reduction of cell proliferation.

Arthritis, Rheumatoid↗
PubMed2006

[Simvastatin inhibits hypertension-induced cardiac hypertrophy in rats through activation of heme oxygenase-1/carbon monoxide pathway].

To investigate the anti-cardiac hypertrophic mechanism of statins, thirty-eight male Wistar rats were randomly allocated to four groups. Rats in model group received nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NNA) 15 mg/(kg.d) by peritoneal injection. Rats in simvastatin treatment groups were given simultaneously L-NNA as those in model group and simvastatin 5 or 30 mg/(kg.d) intragastrically respectively. Rats in control group received the same volume of normal sodium. Left ventricular function, left ventricular mass index (LVMI), the content of brain natriuretic peptide (BNP) in plasma and myocardium, myocardial hydroxyproline and heme oxygenase activity were determined after 6 weeks. The results showed that rats in model group developed significant cardiac hypertrophy associated with reduced left ventricular function compared with the control group. However, compared with the model group, L-NNA-induced cardiac hypertrophy of rats was significantly relieved in simvastatin treatment groups, associated with improved left ventricular function, decreased LVMI, lower BNP levels in plasma and myocardium, lower content of myocardial hydroxyproline, and increased myocardial heme oxygenase (HO) activity. In cultured rat neonatal cardiomyocytes, simvastatin (30 or 100 mumol/L) significantly increased heme oxygenase-1 (HO-1) mRNA expression, HO activity as well as the production of CO in cardiomyocytes. Cultured with zinc protoporphyrin, a HO inhibitor, or simvastatin alone did not change [(3)H]leucine uptake of cardiomyocytes. However, cocultured with simvastatin significantly inhibited the cardiomyocyte [(3)H]leucine uptake induced by angiotensin II in a concentration-dependent manner. Cotreatment with zinc protoporphyrin significantly abolished the suppressive effect of simvastatin on cardiomyocyte [(3)H]leucine uptake. These data suggest that the activation of HO-1/CO pathway may be one of the important mechanisms by which statins inhibit cardiac hypertrophy caused by hypertension.

Angiotensins↗
PubMed2005

[Effect of simvastatin on the proliferation of human omental preadipocytes and caspase-3 expression].

OBJECTIVE: To explore the effect of simvastatin on the cell cycle and caspase-3 expression in human omental preadipocytes. METHODS: The preadipocytes were randomly divided into a blank group, a 10(-5) mol/L simvastatin group, and a 10(-4) mol/L simvastatin group. Each group was incubated with different concentrations of simvastatin for 48 hours. MTT method was used to analyze the effect of simvastatin on the proliferation. Distribution of the cell cycle was measured by flow cytometric. Caspase-3 expression was examined by cyto- immunochemistry. RESULTS: After being induced to differentiate for 16 days the human omental preadipocytes developed to mature adipocyte penotypes with lipid droplet. Simvastatin 10(-4) mol/L had significant anti-proliferation effect. Flow cytometric analysis showed the cell cycle was blocked in G0/G1 phase and caspase-3 positive cells increased dramatically. CONCLUSION: Simvastatin may block the cells in G0/G1 phase, and induce caspase-3 expression, which may trigger apoptosis.

Adipocytes↗
PubMed1991

[Preventive effect of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis in cholesterol-fed rabbits].

A study was made on the effect of simvastatin (the generic name of MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on coronary atherosclerosis in cholesterol-fed rabbits with focus on the serum lipids and morphology. Twenty-seven Japanese white rabbits were divided according to dosage of simvastatin into four groups as follows, group P (placebo, 5 rabbits), group MK 1 (simvastatin 1mg/kg, 5 rabbits), group MK 3 (simvastatin 3mg/kg, 6 rabbits) and group MK 5 (simvastatin 5mg/kg, 5 rabbits). They were placed on a 0.5% cholesterol atherogenic diet for 16 weeks and measurements were made of the concentration of serum lipids weekly. After sacrifice, the degree of surface involvement (SI) of aorta stained with Sudan III and the degree of coronary stenosis (CS) of the left circumflex artery were measured using an image-processing system. Serum total cholesterol (TC) level and beta-lipoprotein level decreased dose-dependently in MK groups compared with group P. High density lipoprotein cholesterol level increased in groups MK 3 and MK 5 slightly. Triglyceride level decreased in groups MK 3 and MK 5. The progressions of SI and CS were suppressed in MK groups dose-dependently. Integrated TC, that is, sum of the serum TC values obtained at each week multiplied by 7 corresponded more closely to CS than SI. Intimal thickening constructed from large foam cells originated from macrophages and proliferating smooth muscle cells included lipid droplets in MK groups was almost similar in group P. But it was likely that lipid droplets in each smooth muscle cell in MK groups were less than in group P. In conclusion, the development of coronary atherosclerosis in cholesterol-fed rabbits was suppressed dose-dependently by simvastatin and it was suggested that this preventive effect was due to reducing the integrated TC and local action to vessel walls by simvastatin. (Fukuoka Acta Med.)

Animals↗
PubMed1990

[The efficacy and tolerance of simvastatin and fenofibrate in primary hypercholesterolemia].

The effects of simvastatin and fenofibrate on blood lipids and the side-effects of these two drugs were compared in a double-blind trial involving 184 adults with primary hypercholesterolemia (total cholesterol levels: 3.87 +/- 1.02 g/l in the simvastatin group, 3.78 +/- 0.79 g/l in the fenofibrate group; N.S.). During a 10-week period, the patients received either fenofibrate 200 mg twice daily or simvastatin 20 mg once daily with doubling of the dosage at week 6 if the LDL-cholesterol level remained above 1.40 g/l. Simvastatin significantly (P less than 0.01) reduced total cholesterol by -29.9 percent, LDL-cholesterol by -35.4 percent, apoprotein B by -27.3 percent and triglycerides by -16.7 percent. Fenofibrate significantly (P less than 0.01) reduced total cholesterol by -19.2 percent, LDL-cholesterol by -22.3 percent apoprotein B by 13.9 percent and triglycerides by 28.9 percent. Reduction of the first 3 parameters was significantly (P less than 0.01) greater with simvastatin and reduction of triglycerides significantly greater with fenofibrate. Apoprotein A1 levels were increased by fenofibrate (+ 7.4 percent) but not by simvastatin. Side-effects occurred with a frequency of 6 percent under simvastatin and 9 percent under fenofibrate.

Adolescent↗
PubMed1989

Comparison between low-dose simvastatin and cholestyramine in moderately severe hypercholesterolemia.

In a 6-week multicenter study, we compared the efficacy and tolerance of a treatment with 10 mg of simvastatin, a new inhibitor of the HMG-CoA reductase to that of 12 g cholestyramine in 145 patients whose total cholesterol remained between 250 and 350 mg/dl after 4 weeks of a standard lipid-lowering diet. The decrease in total cholesterol reached 21% in the simvastatin group and 16% in the cholestyramine group (p less than 0.01) while the LDL-cholesterol decreased respectively by 30% and 25%. HDL cholesterol increased by 11% in the simvastatin group and by 7% in the cholestyramine group. The ratios of total to HDL cholesterol and LDL to HDL cholesterol decreased by 28.1% and 35.8% respectively with simvastatin and by only 19.5% and 27.9% respectively with cholestyramine. Triglycerides decreased by 5.8% with simvastatin and increased by 8.5% with cholestyramine. Significantly less adverse experiences were observed with simvastatin than with cholestyramine. Simvastatin at the dosage of 10 mg appeared to be at least as efficient as 12 g of cholestyramine and generally better tolerated.

Adolescent↗
PubMed1995

The sensitivity of leukemic bone marrow to simvastatin is lost at remission: a potential purging agent for autologous bone marrow transplantation.

BACKGROUND: Autologous bone marrow transplantation (ABMT) is frequently used in the treatment of malignant disease but carries the risk of reintroducing tumor cells into the patient. Methods are required for removing malignant cells from harvested bone marrow (BM) without impairing hematopoietic reconstitution. We have shown that simvastatin is toxic to leukemic progenitor cells at a concentration that conserves normal BM progenitors and may be of use clinically as a novel BM purging agent. METHODS: A two-stage culture system was used to compare the effects of simvastatin on both normal BM progenitor and primary acute myeloid leukemia (AML) cells. AML cells and normal BM mononuclear cells were incubated for 18 hours in suspension culture with 10 micrograms per mL simvastatin and the numbers of surviving clonogenic progenitor cells assayed in semisolid agar culture. RESULTS: Following simvastatin treatment of 18 AML cell populations, the mean surviving fraction of progenitor cells was 21.3 +/- 4.8% ( +/- standard error of the mean [SEM]). In contrast, the mean survival of normal BM progenitors from 16 donors was 89.6 +/- 8.6% ( +/- SEM). Samples were taken from 6 AML patients before treatment and after remission of disease had been induced by chemotherapy. In 5 of these cases the AML sample was significantly more sensitive to simvastatin than the remission sample, 4 of the 5 showed > 80% difference in progenitor cell survival. CONCLUSIONS: AML progenitor cells are sensitive to a short-term exposure to simvastatin that spares normal BM hematopoietic progenitor cells. We conclude that simvastatin may be an effective in vitro purging agent in ABMT for AML.

Acute Disease↗
PubMed1994

Comparative efficacy and safety of micronized fenofibrate and simvastatin in patients with primary type IIa or IIb hyperlipidemia.

BACKGROUND: Few studies have been performed to compare fenofibrate, a second-generation fibrate, and simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. This study was aimed to compare the efficacy of both drugs in reducing atherogenic risk factors in type IIa or IIb hyperlipidemia. METHODS: Sixty-three patients entered this single-center, double-blind, crossover trial. Sixty patients (32 with type IIa and 28 with type IIb hyperlipidemia) were randomized to treatment for 3 months with a single daily 200-mg dose of micronized fenofibrate or 20 mg of simvastatin and then changed to the alternative treatment for a further 3-month period. RESULTS: After the first treatment period, in both types IIa and IIb, fenofibrate and simvastatin produced similar significant reductions in levels of total cholesterol and low-density lipoprotein cholesterol; high-density lipoprotein cholesterol levels were increased with both drugs in type IIb. Only fenofibrate decreased total triglyceride levels in type IIb, Lp(a) lipoprotein levels in patients with high baseline values, and fibrinogen. After the second period of treatment, in both types IIa and IIb, switching from fenofibrate to simvastatin resulted in a further reduction in total cholesterol and low-density lipoprotein cholesterol levels. The difference in the response of the two treatments on levels of total triglycerides, Lp(a) lipoprotein, and fibrinogen was confirmed after changing over to the alternative treatment. This short-term study showed few adverse effects for both drugs. CONCLUSIONS: Fenofibrate and simvastatin provide similar variations on total cholesterol and low-density lipoprotein cholesterol levels after a 3-month treatment period, with simvastatin having the capacity to decrease these measures further when administered after fenofibrate. However, fenofibrate exhibits a significant effect on other established risk factors, such as total triglyceride, fibrinogen, and Lp(a) lipoprotein levels, and accordingly has a broader spectrum of activity than simvastatin.

Adolescent↗
PubMed1993

Efficacy and tolerability of simvastatin 20 mg vs pravastatin 20 mg in patients with primary hypercholesterolemia. European Study Group.

The safety, tolerability, and efficacy of 20 mg daily doses of simvastatin and pravastatin were compared in this double-blind, randomized trial of 210 patients with primary hypercholesterolemia. Simvastatin was found to produce significantly greater mean percent reductions from baseline in total cholesterol (28% versus 21%), LDL cholesterol (38% versus 29%), and apolipoprotein B concentrations (25% versus 17%) than did pravastatin, and a greater percentage of patients receiving simvastatin (94% versus 80%) had at least a 20% reduction in LDL cholesterol. Both simvastatin and pravastatin produced similar significant mean percent reductions from baseline in triglyceride concentrations (14% and 11%) and significant mean percent increases in the concentrations of HDL cholesterol (7% for both) and apolipoprotein A-I (4% for both). Resulting reductions in the ratios of total cholesterol: HDL cholesterol, LDL cholesterol: HDL cholesterol, and apolipoprotein B: apolipoprotein A-I were significantly greater in the simvastatin group. Both simvastatin and pravastatin were well tolerated. The incidence and severity of clinical and laboratory adverse experiences were similar in both groups, and none were classified as serious. The results of this study confirm the results of prior studies that have found simvastatin to produce lipid-lowering effects superior to those of pravastatin when administered at equivalent mg doses, while demonstrating similar safety profiles.

Adolescent↗
PubMedDate not supplied

Changes in biliary lipid secretion and cholic acid kinetics induced by diet, diet plus simvastatin and diet plus ursodeoxycholic acid in obese subjects.

The aim of this work was to evaluate and compare the effects of a low calorie diet (1026 kcal), simvastatin and ursodeoxycholic acid administration on biliary lipid secretion and cholic acid kinetics in dieting obese subjects. We studied 6 obese subjects before and after four weeks of a hypocaloric diet alone, after four weeks of diet plus ursodeoxycholic acid (900 mg/day) and after four weeks of diet plus simvastatin (40 mg/day), according to a Latin square design. The cholesterol saturation index was increased after diet alone, significantly reduced with diet plus ursodeoxycholic acid (p < 0.01), and unchanged during simvastatin administration. While the cholesterol output was reduced by all three regimens, diet plus ursodeoxycholic acid caused a significantly greater decrease than diet alone (p < 0.01). Cholic acid synthesis and bile acid secretion were decreased by diet and diet plus simvastatin (p < 0.05), but neither was affected by ursodeoxycholic acid. For cholic acid, all three treatments, but especially diet alone and diet plus simvastatin (p < 0.05), reduced the pool size; all three regimens also increased the turnover rate, but this was significant only for ursodeoxycholic acid (p < 0.01). Our study shows that, in obese patients, a hypocaloric diet reduces cholesterol-holding biliary lipid output and consequently increases the cholesterol saturation index. The addition of simvastatin to a hypocaloric dietary regimen reduces cholesterol secretion, but without variation in bile acid and phospholipid output thus the cholesterol saturation index remains unchanged. When ursodeoxycholic acid is added to the dietary regimen, it reduces cholesterol secretion, while maintaining bile acid output and, thus, lowers the cholesterol saturation index. Unlike simvastatin, ursodeoxycholic acid prevents the drop in cholic acid synthesis induced by a low calorie diet.

Adult↗