(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Diabetes-Mellitus--Type-2

Topics: Aged; Anti-Arrhythmia Agents; Anticholesteremic Agents; Atrial Fibrillation; Blood Pressure; Cardiovascular Surgical Procedures; Chronic Disease; Cross Infection; Diabetes Mellitus, Type 2; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glycated Hemoglobin; Humans; Indoles; Male; Methicillin-Resistant Staphylococcus aureus; Metoprolol; Middle Aged; Surgical Wound Infection; Systole

Patients with type 2 diabetes are at increased cardiovascular risk. The aim was to explore whether the impaired arterial wall characteristics typical of these patients could be improved by the unique beneficial effects of a very low-dose combination of fluvastatin and valsartan (low-flu/val).. Forty middle-aged males (50.4±6.1years) with type 2 diabetes were recruited to a double-blind, randomized study. Patients (N=20) received low-flu/val (10/20mg) or placebo (N=20) over 30days in addition to their regular therapy. Brachial artery flow mediated dilation (FMD), common carotid artery pulse wave velocity (PWV) and β-stiffness were assessed before and after treatment, and 3 and 6months after treatment discontinuation. The treatment was then repeated.. Arterial wall characteristics significantly improved. After 30days of intervention, FMD increased from 2.4±0.3 to 4.2±0.3 (p<0.001), PWV decreased from 6.4±0.1 to 5.8±0.2 (p<0.001) and β stiffness decreased from 7.8±0.4 to 6.7±0.4 (p<0.001). Lipids and arterial pressure did not change. After treatment discontinuation, the beneficial effects decreased over the following months. The repetition of treatment completely regained the initial benefits. No changes were observed in the placebo group.. Low-flu/val added on-top of optimal therapy substantially improves arterial wall characteristics in patients with type 2 diabetes.

Topics: Angiotensin II Type 1 Receptor Blockers; Arteries; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Endothelium, Vascular; Fatty Acids, Monounsaturated; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Pulse Wave Analysis; Ultrasonography; Valsartan; Vascular Stiffness; Vasodilation

Ezetimibe, a cholesterol-absorption inhibitor, significantly lowers low-density lipoprotein cholesterol (LDL-C) when administered in addition to statin treatment. The effect of ezetimibe on the incidence and progression of vascular disease is elusive. The objective of the study was to examine the effects of fluvastatin plus ezetimibe on lipoprotein subfractions in patients with type 2 diabetes and/or coronary heart disease.. Ninety patients with LDL-C between 100 and 160 mg dL(-1) were enrolled in this prospective, randomized, single-blind, single-centre study. A total of 84 patients were treated with either fluvastatin 80 mg (n = 28) alone or in combination with ezetimibe 10 mg (n = 56) for 12 weeks to determine the effects on lipids, apolipoproteins and LDL subfractions by equilibrium density gradient ultracentrifugation. This study is registered with ClinicalTrials.gov, number NCT00814723.. Total cholesterol, LDL-C and apolipoprotein B were significantly more reduced in the combined therapy group. High density lipoproteins increased in the fluvastatin-only group and decreased in the combined therapy group. There was a significant difference between the two groups in buoyant and intermediate, but not in dense LDL particles.. Addition of ezetimibe to fluvastatin resulted in a further reduction of buoyant and intermediate, but not of dense LDL compared with fluvastatin alone.

Topics: Aged; Anticholesteremic Agents; Apolipoproteins B; Azetidines; Biomarkers; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Ezetimibe; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Indoles; Lipoproteins; Lipoproteins, LDL; Male; Middle Aged; Prospective Studies

Mixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day.. Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA.. The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05).. Our preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.

Topics: Antihypertensive Agents; Apolipoprotein B-48; Blood Glucose; Blood Pressure; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Reducing; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glycated Hemoglobin; Humans; Hyperlipidemia, Familial Combined; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Indoles; Lipids; Male; Middle Aged

Both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as well as peroxisome proliferator-activated receptor (PPAR)alpha activators (fibrates) proved to be effective in the primary and secondary prevention of cardiovascular diseases. The benefits of hypolipemic therapy in cardiovascular diseases cannot be explained only by the lipid-lowering potential of these agents. The aim of this study was to clarify the effect of hypolipemic agents on proinflammatory cytokine release from human monocytes in relationship with their action on plasma levels of sensitive systemic marker of low-grade vascular inflammation. Plasma lipid and high-sensitivity C-reactive protein (hsCRP) levels, and the release of tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta from monocytes were assessed at baseline and 30 and 90 days following randomization of IIa dyslipidemic patients into fluvastatin or simvastatin groups and randomization of type IIb dyslipidemic patients to the micronized form of either ciprofibrate or fenofibrate. Lipopolysaccharide-stimulated monocytes from dyslipidemic patients released significantly more TNFalpha (types IIa and IIb dyslipidemias) and interleukin-1beta (type IIa dyslipidemia) in comparison with monocytes in 59 age-, sex-, and weight-matched control subjects. Their baseline hsCRP levels were also higher. Both statins and fibrates reduced the release of TNFalpha and interleukin-1beta, and lowered plasma hsCRP levels. The effects of hypolipemic agents on cytokine release and plasma hsCRP were unrelated to their lipid-lowering action. Our results have demonstrated that type IIa and IIb dyslipidemic patients exhibit the abnormal pattern of TNFalpha and interleukin-1beta production by activated monocytes. Both HMG-CoA reductase inhibitors and PPARalpha activators normalize monocytic secretion of these cytokines, and this action may partially contribute to the systemic antiinflammatory effect of hypolipemic agents. The statin- and fibrate-induced suppression of proinflammatory cytokine release from monocytes seems to play a role in their beneficial effect on the incidence of cardiovascular events.

Topics: Adult; Anticholesteremic Agents; C-Reactive Protein; Clofibric Acid; Cytokines; Diabetes Mellitus, Type 2; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fibric Acids; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Indoles; Inflammation; Interleukin-1; Male; Middle Aged; Monocytes; PPAR alpha; Tumor Necrosis Factor-alpha

Fluvastatin reduces atherogenic dense low-density lipoprotein (dLDL) in patients with type 2 diabetes mellitus (T2DM). dLDLs are associated with platelet-activating factor acetyl hydrolase (PAF-AH), an enzyme involved in inflammation and related to coronary artery disease (CAD). The association of preexisting CAD and PAF-AH and the effect of fluvastatin on enzyme activity is investigated in a placebo-controlled trial in patients with T2DM. A multicenter, double-blind, randomized comparison of fluvastatin XL (80 mg) (n = 42) and placebo (n = 47), each given once-daily for 8 wk, in 89 patients with T2DM, was conducted. At baseline and on treatment, lipoproteins, including lipoprotein (a) [Lp(a)] and LDL subfractions, and the activity of PAF-AH were measured. Increasing PAF-AH activity was significantly associated with a positive history of CAD (+0.7% per IU/liter PAH-AH; P = 0.010), the odds ratio estimate adjusted for age, gender, and body mass index of the highest quartile being 10.6 (P = 0.036). At baseline and at study end, PAF-AH activity was associated with the apolipoprotein B (apoB) content in dLDL (LDL-5 and LDL-6) (r = 0.447; P < 0.001 and r = 0.651; P < 0.001, respectively) and with non-HDL cholesterol at baseline (r = 0.485; P < 0.001). However, after additional adjustment for apoB in dLDL and non-HDL cholesterol at baseline, the odds ratio increment for CAD across PAF-AH quartiles was 2.09 (95% confidence interval, 1.02-4.29; P = 0.043). Fluvastatin treatment decreased the activity of PAF-AH by 22.8% compared with an increase of 0.4% in the placebo group (P < 0.001). This effect was independent of changes of Lp(a) concentrations. In patients with T2DM, PAF-AH activity is associated with a positive history of CAD. Fluvastatin not only decreases atherogenic dLDL but also PAF-AH activity, emphasizing the significance of fluvastatin treatment in T2DM. The antiatherogenic potential of fluvastatin in T2DM may thus be greater than expected from its effects on LDL-C and triglycerides alone.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Aged; Anticholesteremic Agents; Apolipoproteins B; Cholesterol; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Enzyme Activation; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Indoles; Male; Middle Aged; Placebos

The purpose of this study was to investigate the lipid-lowering and anti-oxidative effects of fluvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in type 2 diabetic patients. Six patients (3 men and 3 women, mean age = 56.2) took 20 mg of fluvastatin once daily (at night) for 12 weeks. Several markers of oxidative stress were then measured in these patients including plasma cholesterol oxidation products, i.e. oxysterols, and the levels of circulating adhesion molecules. Plasma total cholesterol levels were reduced by 12.3% in these individuals after 4 weeks of treatment, with levels remaining below 220 mg/dl for the entire treatment period. LDL levels were significantly reduced at 4 (18.1%) and 12 weeks (16.1%), and triglyceride levels were significantly reduced after 8 (22.5%) and 12 (37.7%) weeks of treatment. HDL-C levels increased from 50.7 +/- 15.4 prior to treatment to 63.8 +/- 24.3 mg/dl after 12 weeks of treatment, though this increase was not statistically significant. Lipid hydroperoxide, thiobarbituric acid-reactive substance (TBARS), and oxysterol levels were also reduced, suggesting that fluvastatin also had anti-oxidative effects. Finally, VCAM-1 levels were similarly reduced by fluvastatin treatment. We conclude that fluvastatin safely improves the plasma lipid profile in type 2 diabetic patients with hyperlipidemia. We speculate that this drug might be doubly effective in reducing atherosclerosis and cardiac events in these patients as a result of its demonstrated anti-oxidative effects and its ability to reduce VCAM-1 levels.

Topics: Antioxidants; Cholesterol; Diabetes Mellitus, Type 2; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Middle Aged; Oxidation-Reduction; Vascular Cell Adhesion Molecule-1

Diabetes risk is often complicated by a mixed hyperlipoproteinemia not sufficiently controlled by a single antihyperlipidemic drug; however, there are some concerns about the safety of combined statin and fibrate treatments.. The aim of this study was to compare the efficacy and safety profile of fluvastatin + fenofibrate combination therapy and those of fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus (DM), and coronary heart disease (CHD) (ie, high risk for cardiovascular disease [CVD]).. This 12-month, randomized, double-blind, controlled trial was conducted at the University of Pavia, Pavia, Italy. Patients aged 18 to 80 years with combined hyperlipidemia, type 2 DM, and CHD were randomly assigned to receive combination therapy with extended-release fluvastatin 80 mg + micronized fenofibrate 200 mg or monotherapy with extended-release fluvastatin 80 mg. All treatments were given in tablet form, once daily with the evening meal, for 12 months. Lipid variables (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) at 6 and 12 months were the primary efficacy variables, and glycemic status (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose, and postprandial plasma glucose levels) at 6 and 12 months was the secondary efficacy variable. Tolerability was assessed using physical examination, including vital-sign assessment, body-weight measurement, electrocardiography, adverse events, and laboratory tests. A pharmacoeconomic analysis of both treatment regimens was also carried out using the incremental cost-effectiveness ratio (ICER).. A total of 48 patients (24 men, 24 women; mean [SD] age, 60 [5] years) were enrolled. After 6 months, all primary efficacy variables, except for TG level, showed significant improvements from baseline only in the combination-therapy group (changes: LDL-C, -25%; HDL-C, +12%; and TC, -19%; all, P < 0.05 vs baseline). After 12 months, lipid variables showed significant improvements over baseline in both groups (all, P < 0.05), except for TG in the monotherapy group. Significant changes in LDL-C, HDL-C, and TG were found in the combination-therapy group (-35%, +34%, -32%, respectively) versus the monotherapy group (-25%, +14%, -17%, respectively; all, P < 0.05 between groups). The change from baseline in HbA(1c) level was significant with combination therapy (-12% vs -7%; P < 0.05). Both treatments were well tolerated, with no significant differences in the incidences of adverse events between the 2 groups. The ICER showed that each 1% decrease in LDL-C level achieved with the fenofibrate + fluvastatin combination added a cost of 14.97 Euros/y (US 12.25 US dollars/y), and each 1% increase in HDL-C level added a cost of 7.48 Euros/y (6.12/y US dollars), over the cost of monotherapy.. In this selected sample of patients with combined hyperlipidemia, type 2 DM, and CHD, the combination of extended-release fluvastatin + micronized fenofibrate was associated with a more improved lipid profile than fluvastatin monotherapy, and was a well-tolerated and cost-effective therapeutic choice to treat these patients at high risk for CVD.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Coronary Disease; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fluvastatin; Hemoglobins, Abnormal; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipids; Male; Middle Aged; Treatment Outcome

To assess efficacy of combination therapy with fluvastatin and fenofibrate in ischemic heart disease (IHD) patients with combined hyperlipidemia and type 2 diabetes.. Patients with IHD and combined hyperlipidemia with (n=56)) or without type 2 diabetes (n=30).. After 8-week diet period the patients were randomized to 4 weeks monotherapy with either fluvastatin (40 mg/day) or micronized fenofibrate (200 mg/day). In patients whose low-density lipoprotein cholesterol (LDL CH) remained > 2,6 mmol/1 and triglycerides (TG) > 2.3 mmol/1 combination of fluvastatin 40 mg/day and fenofibrate 200 mg/day was used for the next 12 weeks.. Target levels of LDL CH and TG were achieved in 75 and 88%, respectively, of diabetics, and in 73 and 88%, respectively, of non-diabetics.. The use of combination of fluvastatin and fenofibrate was more effective then monotherapy for correction of lipid abnormalities in combined hyperlipidemia both in diabetics and non-diabetics with IHD.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fluvastatin; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Male; Middle Aged; Myocardial Ischemia; Treatment Outcome

Arterial stiffness assessed by pulse wave velocity (PWV) predicts all-cause and cardiovascular mortality in diabetic patients with end-stage renal disease. We studied the preventive effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on arterial PWV values in this population.. Twenty-two patients with normal serum lipid levels received fluvastatin (20 mg/day p.o.) or a placebo for 6 months. Their serum lipid levels, serum levels of C-reactive protein (CRP), arterial PWV, and ankle brachial indexes (ABI) were determined before, and 3 and 6 months after taking the medication to evaluate arterial stiffness.. At the beginning of the follow-up, there were no differences in age, blood pressure, body mass index, serum haemoglobin A1c level, serum CRP level, serum lipid levels, PWV or ABI between the placebo- (n=10) and the fluvastatin-treated patients (n=12). After 6 months, the PWV and the serum oxidized low-density lipoprotein cholesterol (LDL-C) level increased significantly (from 1969+/-140 to 2326+/-190 cm/s and 70.4+/-13.8 to 91.8+/-15.5 U/l, respectively) in the placebo-treated patients. However, the fluvastatin group had a significantly reduced PWV (from 1991+/-162 to 1709+/-134 cm/s), oxidized LDL-C serum levels (from 89.0+/-9.6 to 73.0+/-5.8 U/l) and CRP serum levels (from 0.97+/-0.32 to 0.26+/-0.16 mg/dl) compared with those in the placebo group.. Long-term administration of fluvastatin prevents further worsening of arterial biomechanics in haemodialysis patients with type 2 diabetes mellitus, even in the presence of serum lipid levels in the normal range.

Topics: Anticholesteremic Agents; Blood Flow Velocity; Blood Pressure; Body Mass Index; C-Reactive Protein; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fatty Acids, Monounsaturated; Fatty Acids, Nonesterified; Fluvastatin; Glycated Hemoglobin; Humans; Indoles; Phospholipids; Placebos; Renal Dialysis; Triglycerides; Vascular Diseases

The objective of this study was to determine the effect of slow-release (XL) fluvastatin on low density lipoprotein (LDL) subfractions in type 2 diabetes. A multicenter, double-blind, randomized, parallel-group comparison of fluvastatin XL 80 mg (n = 42) and placebo (n = 47), each given once-daily for 8 wk, in 89 patients with type 2 diabetes (HbA1c: 7.2 +/- 1.0%, LDL cholesterol (LDL-C): 3.4 +/- 0.7 mmol/liter, high density lipoprotein cholesterol: 1.1 +/- 0.3 mmol/liter, and triglycerides (TG): 2.4 +/- 1.4 mmol/liter). At baseline and on treatment, plasma lipoproteins were isolated and quantified. Eight weeks of fluvastatin treatment decreased total cholesterol (-23.0%, P < 0.001), LDL-C (-29%, P < 0.001) and TG (-18%, P < 0.001), compared with placebo. At baseline, there was a preponderance of dense LDL (dLDL) (apolipoprotein B in LDL-5 plus LDL-6 > 25 mg/dl) in 79% of patients, among whom fluvastatin decreased all LDL subfractions, reductions in dLDL being greatest (-28%, P = 0.001; cholesterol in dLDL -29%). In patients with low baseline dLDL (apolipoprotein B in LDL-5 plus LDL-6

Topics: Aged; Apolipoproteins; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Indoles; Lipids; Lipoproteins; Lipoproteins, LDL; Male; Middle Aged; Safety

The effects of fluvastatin therapy on parameters of coagulation and fibrinolysis were evaluated in patients with diabetic dyslipidemia in a randomized, placebo-controlled study. Fluvastatin therapy was associated with a small reduction in factor VII coagulant activity, von Willebrand factor, and in plasminogen activator inhibitor 1 and tissue plasminogen activator antigens, but the effects of fluvastatin on hemostatic factors were much less marked than its effects on plasma lipids.

Topics: Analysis of Variance; Anticholesteremic Agents; Blood Coagulation; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fibrinolysis; Fluvastatin; Humans; Hyperlipidemias; Indoles; Lipids; Male; Middle Aged

Human drug interaction studies in vivo are conducted when in vitro and/or animal interactions suggest clinical relevance. Studies in vitro have indicated that the new, entirely synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin affects the metabolism of the nonsteroidal anti-inflammatory drug diclofenac and the oral hypoglycemic tolbutamide. Diclofenac and tolbutamide are both model substrates of the CYP2C isozymes, suggesting that this enzyme could be involved in the underlying mechanism of interaction. The concomitant use of lipid-lowering drugs with oral hypoglycemic agents has been recommended in patients with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, 2 studies were initiated to explore potential pharmacokinetic and pharmacodynamic interactions between fluvastatin, simvastatin, or placebo and the oral hypoglycemic agents tolbutamide (study I) and glyburide (study II), each in 16 healthy subjects. These compounds were selected because of a demonstrated in vitro interaction with tolbutamide and widespread clinical use of glyburide. A further study (study III) was conducted to investigate the potential pharmacokinetic and pharmacodynamic interactions between fluvastatin and glyburide under therapeutic conditions in 32 patients with NIDDM. Single and multiple coadministration of fluvastatin 40 mg or simvastatin 20 mg increased the mean maximum plasma concentration and area under the concentration-time curve of glyburide by about 20%. The pharmacokinetics of tolbutamide were influenced to only a minor extent. Fluvastatin concentration-time profiles were unaffected by tolbutamide or glyburide coadministration. However, the pharmacokinetic interactions between fluvastatin or simvastatin and tolbutamide and glyburide were not associated with clinically relevant changes in blood glucose and insulin concentrations and, therefore, are not considered to be relevant in therapeutic practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Anticholesteremic Agents; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diclofenac; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Glyburide; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Insulin; Lovastatin; Placebos; Simvastatin; Tolbutamide

In this preliminary report of a 20-week trial, 66 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hyperlipidaemia who remained eligible after an 8-week dietary stabilization phase were randomly allocated to receive 20 mg of fluvastatin or placebo once daily for 6 weeks. Fluvastatin was subsequently increased to 20 mg twice daily and administered according to the same schedule, versus placebo, for a further 6 weeks. Both dosages of fluvastatin substantially improved serum lipid profiles compared with baseline and placebo. Both dosages of fluvastatin significantly reduced low-density- and very-low-density-lipoprotein (LDL, VLDL), cholesterol and triglyceride (TG) compared with placebo, and both dosages significantly elevated high-density-lipoprotein (HDL) cholesterol. The ratio of LDL to HDL was also significantly decreased. Amongst the 58 patients who completed the study, there was no evidence either of myopathy or of hepatotoxicity; mean creatine kinase values remained stable in the fluvastatin arm. Fasting glucose, glycosylated haemoglobin, and fructosamine levels were not markedly affected by active treatment. No serious adverse events attributable to the drug were reported. In conclusion, both dosages of fluvastatin appear to be effective and safe in the management of hyperlipidaemia in this outpatient, maturity-onset, diabetic population.

Topics: Adult; Aged; Anticholesteremic Agents; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Lipids; Lipoproteins; Male; Middle Aged; Treatment Outcome

The purpose of this study was to investigate the triglyceride-lowering effect of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in the combined hyperlipidemia of non-insulin-dependent diabetes mellitus (NIDDM). In this double-blind trial, 66 patients with NIDDM (24 men and 42 women, age 37-71), with low-density lipoprotein cholesterol (LDL-C) levels of 130-300 mg/dL (3.4-7.8 mmol/L) and triglyceride (TG) levels of 200-1,000 mg/dL (2.3-11.3 mmol/L) despite an 8-week period of diet modification, were randomized to receive either fluvastatin at 20 mg once daily (at night) or placebo for 6 weeks, followed by an increase of fluvastatin to 20 mg twice daily for an additional 6 weeks of treatment. After 12 weeks, fluvastatin decreased plasma levels of total cholesterol by 19.9% (p < 0.001), LDL-C by 24.3% (p < 0.001), TG by 15.3% (p < 0.01), very low-density lipoprotein cholesterol (VLDL-C) by 19.7% (p < 0.001), apolipoprotein (apo) B by 21.3% (p < 0.001), and apo E by 18.1% (p < 0.05), whereas high-density lipoprotein cholesterol (HDL-C) levels were increased by 4.6% (p < 0.05). Within the intermediate-density lipoprotein cholesterol (IDL-C) fraction, a constituent analysis revealed a total cholesterol reduction of 35% (p < 0.01). Greater decreases in TG were seen in patients who had higher levels of TG at baseline. Slight increases in glycemic indices and body weight were seen in both treatment groups. The occurrence of clinical and laboratory abnormalities was similar with both active treatment and placebo, and no myositis was observed. Slight increases in aspartate (ASAT; mean 5.6 U/L at the higher dose) and alanine (ALAT; mean 5.1 U/L at the higher dose) aminotransferases were not clinically significant. In this first, parallel-group placebo-controlled trial of a reductase inhibitor in a free-living NIDDM population, fluvastatin safely improved the combined TG, VLDL-C, IDL-C, LDL-C, and HDL-C abnormalities associated with NIDDM.

Topics: Adult; Aged; Anticholesteremic Agents; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipids; Male; Middle Aged; Sex Factors; Treatment Outcome

This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of fluvastatin on the lipid profiles of patients with hypertriglyceridemia resulting from non-insulin-dependent diabetes mellitus (NIDDM). Sixty-six NIDDM patients (24 men, 42 women) with low density lipoprotein cholesterol (LDL-C) levels > 3.36 mmol/liter (130 mg/dL) and triglyceride (TG) levels of 2.3-11.3 mmol/liter (200-1,000 mg/dL) after an 8-week period of Step I diet were given fluvastatin, 20 mg every PM for 6 weeks followed by 20 mg twice daily for an additional 6 weeks, or placebo. By weeks 9-12, fluvastatin decreased plasma LDL-C levels by 24.3% (p < 0.001) and plasma TG by 15.3% (p < 0.01). High density lipoprotein cholesterol levels increased by 4.6% over the same interval (p < 0.05). Fluvastatin treatment was not associated with abnormalities in the indices of glycemic control or clinically important abnormalities in laboratory values. Fluvastatin is an effective treatment of combined elevations of TG and LDL-C in NIDDM.

Topics: Anticholesteremic Agents; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipids; Lipoproteins; Male; Safety; Time Factors

To investigate how statins reduce cardiovascular mortality in patients with type 2 diabetes (T2DM) in a dose-, class-, and use intensity-dependent manner.. We used an inverse probability of treatment-weighted Cox hazards model, with statin use status as a time-dependent variable, to estimate the effects of statin use on cardiovascular mortality.. Adjusted hazard ratio [aHR; 95% confidence interval (CI)] for cardiovascular mortality was 0.41 (0.39-0.42). Compared with nonusers, pitavastatin, pravastatin, simvastatin, rosuvastatin, atorvastatin, fluvastatin, and lovastatin users demonstrated significant reductions in cardiovascular mortality [aHRs (95% CIs) = 0.11 (0.06, 0.22), 0.35 (0.32, 0.39), 0.36 (0.34, 0.38), 0.39 (0.36, 0.41), 0.42 (0.40, 0.44), 0.46 (0.43, 0.49), and 0.52 (0.48, 0.56), respectively]. In Q1, Q2, Q3, and Q4 of cDDD-year, our multivariate analysis demonstrated significant reductions in cardiovascular mortality [aHRs (95% CIs) = 0.63 (0.6, 0.65), 0.44 (0.42, 0.46), 0.33 (0.31, 0.35), and 0.17 (0.16, 0.19), respectively; P for trend < 0.0001]. The optimal statin dose daily was 0.86 DDD, with the lowest aHR for cardiovascular mortality of 0.43.. Persistent statin use can reduce cardiovascular mortality in patients with T2DM; in particular, the higher is the cDDD-year of statin, the lower is the cardiovascular mortality. The optimal statin dose daily was 0.86 DDD. The priority of protective effects on mortality are pitavastatin, rosuvastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and lovastatin for the statin users compared with non-statin users.

Topics: Atorvastatin; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Pravastatin; Primary Prevention; Rosuvastatin Calcium; Simvastatin

Accumulating evidence has shown that diabetic patients are increasing in number, and renal and cardiovascular complications are the most common cause of death in diabetic patients. Thus, it would be of considerable value to identify the mechanisms involved in the progression of renal impairment and cardiovascular injury associated with diabetes. Recent evidence also indicated that multifactorial intervention is able to reduce the risk of cardiovascular disease and death among patients with diabetes and microalbuninuria. In this pilot study, we examined the effects of intensified multifactorial intervention, with tight glucose regulation and the use of valsartan and fluvastatin on ambulatory blood pressure (BP) profile, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR), in 20 hypertensive patients (16 male and 4 female) with type 2 diabetes mellitus and overt nephropathy. After 12 months of intensified treatment, office BP, fasting plasma glucose (FPG), and low-density lipoprotein cholesterol (LDLC) were significantly decreased compared to baseline (systolic blood pressure (SBP), 130 ± 2 vs. 150 ± 1 mmHg; diastolic blood pressure (DBP), 76 ± 1 vs. 86 ± 1 mmHg; FPG, 117 ± 5 vs. 153 ± 7 mg/dl; LDLC, 116 ± 8 vs. 162 ± 5 mg/dl, P < 0.0001). Also, compared to the baseline values, the daytime and nighttime ambulatory BP and short-term BP variability were significantly decreased after 12 months. Furthermore, while eGFR was not altered (44.3 ± 5.1 vs. 44.3 ± 6.5 ml/min/1.73 m(2), not significant (NS)), UACR showed a significant reduction after 12 months of intensified treatment (1228 ± 355 vs. 2340 ± 381 mg/g-cr, P < 0.05). These results suggest that the intensified multifactorial intervention is able to improve ambulatory BP profile, preserve renal function, and reduce urinary albumin excretion in type 2 diabetic hypertensive patients with overt nephropathy.

Topics: Albuminuria; Anticholesteremic Agents; Antihypertensive Agents; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Comorbidity; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glomerular Filtration Rate; Heart Rate; Humans; Hypertension; Indoles; Kidney; Lipids; Male; Middle Aged; Pilot Projects; Prospective Studies; Regression Analysis; Tetrazoles; Valine; Valsartan

Topics: Antioxidants; Brachial Artery; C-Reactive Protein; Cholesterol; Diabetes Mellitus, Type 2; Endothelium, Vascular; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Ultrasonography; Vasodilation

A diabetic patient may suffer simultaneously from cardiovascular disease; thus, lipid-lowering or anti-hypertensive agents could be given together with nateglinide. The pharmacokinetics of nateglinide were investigated in the presence and absence of HMG-CoA reductase inhibitors (fluvastatin, lovastatin) and calcium channel blockers (verapamil, nifedipine) in rabbits. A pharmacokinetic modeling approach was used to quantify the effects of the drugs that significantly influenced the pharmacokinetics of nateglinide. Fluvastatin and nifedipine shifted the time course of serum nateglinide concentrations upwards; there was no significant change with verapamil or lovastatin. The C(max) and AUC(inf) increased 1.5- (p<0.05) and 1.3-fold in the presence of fluvastatin and 1.8- (p<0.01) and 2.4-fold (p<0.01) in the presence of nifedipine, respectively. In a simultaneous nonlinear regression, fluvastatin and nifedipine decreased the elimination rate constant, by 76% and 32%, respectively. Fluvastatin and nifedipine increased the systemic exposure of nateglinide in rabbits, probably due to their inhibitory action on the metabolism of nateglinide by CYP2C5 (human CYP2C9). The concomitant use of fluvastatin and/or nifedipine with nateglinide is quite likely; therefore, the clinical consequences of long-term treatments must be considered.

Topics: Animals; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Calcium Channel Blockers; Cyclohexanes; Cytochrome P-450 CYP2C9; Cytochrome P450 Family 2; Diabetes Mellitus, Type 2; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Indoles; Lovastatin; Male; Nateglinide; Nifedipine; Phenylalanine; Rabbits; Steroid 21-Hydroxylase; Verapamil

Apolipoprotein E (APOE) genotypes have been associated with variations in plasma-lipid levels and with response to statins, although the influence of APOE on the response to statins remains controversial, especially in patients with diabetes. We sought to evaluate the association of the APOE genotype with the low-density lipoprotein cholesterol (LDLc)-lowering response to statins, in a large population-based cohort of patients with diabetes.. A total of 1383 patients, commencing statins between 1990 and 2006, were identified from the Genetics of Diabetes Audit and Research in Tayside Scotland database. Statin response was determined both by the minimum LDLc achieved, and by the failure of the patients to reach a clinical target LDLc (< or =2 mmol/l). APOE genotype and potential confounding covariates were entered into the linear and logistic regression models.. We found an association of APOE genotypes with both baseline and treatment responses. E2 homozygotes achieved lower LDLc levels (mean 0.6; confidence interval: 0.1-1.1 mmol/l) than E4 homozygotes (mean 1.7; confidence interval: 1.4-1.9 mmol/l; P=2.96 x 10). Minimum LDLc was associated by a linear trend with genotype. This relationship remained statistically significant after adjustment for baseline LDLc, adherence, duration, dose, smoking, and age. None of the E2 homozygotes failed to reach the target LDLc, compared with 32% of the E4 homozygotes (P=5.3 x 10).. This study demonstrates the potential clinical value of the APOE genotype as a robust marker for LDLc responses to statin drugs, which might contribute to the identification of a particularly drug-resistant subgroup of patients. This marker provides information over and above baseline lipid levels.

Topics: Anticholesteremic Agents; Apolipoproteins E; Cholesterol, LDL; Cohort Studies; Diabetes Mellitus, Type 2; Fatty Acids, Monounsaturated; Female; Fluvastatin; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Longitudinal Studies; Male; Middle Aged; Pravastatin; Pyridines; Retrospective Studies; Scotland; Simvastatin; Treatment Outcome

Angiotensin II (Ang II) is able to induce free radical generation in neutrophils, which is more elevated in neutrophils of patients with hypercholesterolemia (HC). In addition, the signal processing through angiotensin I (Ang I) receptors is altered. In present study, we compared the Ang II-triggered free radical generation of neutrophils obtained from patients with relatively isolated forms of metabolic syndrome (MS) with membrane-bound cholesterol content and membrane fluidity. We determined the enhancement of Ang II-induced superoxide anion and leukotriene C(4) (LTC(4)) generation, membrane fluidity and cell-bound cholesterol content of neutrophils obtained from 12 control subjects, 11 patients with obesity (Ob), 10 patients with type 2 diabetes mellitus (t2-DM) and 12 patients with HC. The alteration of signal processing was studied after preincubation with different inhibiting drugs. Superoxide anion, LTC(4) production and membrane rigidity were increased in the following order: control < Ob < t2-DM < HC. Both Ang II-induced superoxide anion and LTC(4) generation were decreased in control cells by pertussis toxin and fluvastatin (Flu), whereas in each patient group, mepacrin, verapamil and Flu were effective, suggesting alterations in signal pathways, which may be attributed to isoprenylation. The enhancement of superoxide anion and LTC(4) generation correlated significantly with membrane rigidity, independently from the experimental groups and membrane-bound cholesterol content. Membrane rigidity of neutrophils, obtained from patients with MS, plays a role in Ang II-induced free radical generation independent of intracellular cholesterol homeostasis.

Topics: Adult; Angiotensin I; Angiotensin II; Anticholesteremic Agents; Cholesterol; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Fatty Acids, Monounsaturated; Female; Fluvastatin; Homeostasis; Humans; Hypercholesterolemia; Indoles; Leukotriene C4; Male; Membrane Fluidity; Metabolic Syndrome; Middle Aged; Neutrophils; Pertussis Toxin; Protein Prenylation; Quinacrine; Signal Transduction; Superoxides; Vasoconstrictor Agents; Vasodilator Agents; Verapamil

An open-label prospective cross-over trial was performed to evaluate the antioxidative effect of fluvastatin in Japanese type 2 diabetics with hyperlipidemia. The study subjects were 10 patients who were on pravastatin (10 mg/day) or simvastatin (5 mg/day). After at least 12 weeks of continuous pravastatin or simvastatin therapy, the drugs were washed out for 12 weeks and replaced with fluvastatin (30 mg/day), then the treatment was continued for another 12 weeks. Total cholesterol and LDL cholesterol were efficiently and comparably reduced by all three statin agents. There were no differences in serum parameters of oxidative stress such as malondialdehyde-modified low-density lipoprotein, thiobarbituric acid-reactive substances, and 8-iso-prostaglandin F2alpha between pravastatin/simvastatin and fluvastatin. However, fluvastatin, but not pravastatin/simvastatin, significantly reduced 3,5,7-cholestatriene in erythrocyte membrane, representing the extent of membrane cholesterol peroxidation. Our data demonstrated that fluvastatin has a unique anti-oxidative effect in patients with type 2 diabetes and hyperlipidemia, compared with other statins.

Topics: Aged; Antioxidants; Cholestenes; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Erythrocyte Membrane; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypoglycemic Agents; Indoles; Male; Middle Aged; Oxidative Stress; Pravastatin; Prospective Studies; Simvastatin; Thiobarbituric Acid Reactive Substances

Topics: Anticholesteremic Agents; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus, Type 2; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Myocardial Infarction; Risk Factors; Secondary Prevention

Topics: Adult; Aged; Anticholesteremic Agents; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Data Interpretation, Statistical; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Lipid Metabolism; Lipids; Male; Middle Aged; Time Factors; Triglycerides

Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques. Low-density lipoprotein (LDL) was found to deposit strongly at the proteoheparan sulfate-coated surface, particularly in the presence of Ca(2+), apparently through complex formation 'proteoglycan-LDL-calcium'. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. HDL bound to heparan sulfate proteoglycan protected against LDL deposition and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL was able to decelerate the ternary complex deposition and to disrupt newly formed nanoplaques. Therefore, HDL attached to its proteoglycan receptor sites is thought to raise a multidomain barrier, selection and control motif for transmembrane and paracellular lipoprotein uptake into the arterial wall. The molecular arteriosclerosis model was tested on its reliability in a biosensor application in order to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. The very low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL)/LDL and VLDL/IDL/LDL/HDL plasma fractions from a high-risk patient with dyslipoproteinemia and type 2 diabetes mellitus showed beginning arteriosclerotic nanoplaque formation already at a normal blood Ca(2+) concentration, with a strong increase at higher Ca(2+) concentrations. Nanoplaque formation and size of the HDL-containing lipid fraction remained well below that of the LDL-containing lipid fraction. Fluvastatin, whether applied acutely to the patient (one single 80 mg slow release matrix tablet) or in a 2-months medication regimen, markedly slowed down this process of ternary aggregational nanoplaque build-up and substantially inhibited nanoplaque size development at all Ca(2+) concentrations used. The acute action resulted without any significant change in lipid concentrations of the patient. Furthermore, after nanoplaque generation, fluvastatin, similar to HDL, was able to reduce na

Topics: Adsorption; Arteriosclerosis; Biosensing Techniques; Calcinosis; Calcium; Coated Materials, Biocompatible; Diabetes Mellitus, Type 2; Fatty Acids, Monounsaturated; Fluvastatin; Heparan Sulfate Proteoglycans; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Lipoproteins; Materials Testing; Models, Biological; Particle Size; Silicon Dioxide; Surface Properties; Treatment Outcome

To assess the cost and cost effectiveness of hydroxymethylglutaryl (HMG)-CoA reductase inhibitor (statin) therapy for the primary prevention of major coronary events in the U.S. population with diabetes and LDL cholesterol levels > or =100 mg/dl, especially in the population with LDL cholesterol levels 100-129 mg/dl.. Analyses were performed using population estimates from National Health and Nutrition Examination Survey (NHANES)-III, cost estimates from a health system perspective, statin LDL-lowering effectiveness from pivotal clinical trials, and treatment effectiveness from the diabetic subgroup analysis of the Heart Protection Study.. -There are approximately 8.2 million Americans with diabetes, LDL cholesterol levels > or =100 mg/dl, and no clinical evidence of cardiovascular disease. Each year, statin therapy could prevent approximately 71,000 major coronary events in this population. In the subgroup with LDL cholesterol levels 100-129 mg/dl, the annual cost of statin treatment ranges from 600 to 1,000 US dollars per subject. In the population with LDL cholesterol levels > or =130 mg/dl, the annual cost ranges from 700 to 2,100 US dollars. Annual incremental cost per subject, defined as the cost of statin treatment plus the cost of major coronary events with statin treatment minus the cost of major coronary events without statin treatment, ranges from 480 to 950 US dollars in the subgroup with LDL cholesterol levels 100-129 mg/dl and from 590 to 1,920 US dollars in the population with LDL cholesterol levels > or =130 mg/dl.. Statin therapy for the primary prevention of major coronary events in subjects with type 2 diabetes and LDL cholesterol levels 100-129 mg/dl is affordable and cost effective relative to statin therapy in subjects with higher LDL cholesterol levels.

Topics: Atorvastatin; Cholesterol, LDL; Coronary Disease; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lovastatin; Pravastatin; Pyrroles; Randomized Controlled Trials as Topic; Reproducibility of Results; Sensitivity and Specificity; Simvastatin; United States

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Elasticity; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Kidney Failure, Chronic; Muscle, Smooth, Vascular; Oxidative Stress; Renal Dialysis

A microemulsion formulation of cyclosporin (Neoral) has been developed to overcome the problems of poor and variable absorption of cyclosporin. Neoral is a potent immunosuppressive agent that is highly bound in the plasma. It has been proposed that low-density lipoprotein (LDL) delivers cyclosporin (CsA) to T-lymphocytes via the LDL receptor pathway, where it produces its therapeutic effects. Herein, we report a case of minimal change nephrotic syndrome with type 2 diabetes mellitus treated by Neoral and fluvastatin. A 65-year-old male with a 10-year history of type 2 diabetes mellitus suddenly developed nephrotic syndrome. The potential causative drugs, such as NSAIDs and antibiotics, had not been administered. The laboratory findings were as follows: proteinuria 23 g/day, serum albumin 1.9 g/dl, total cholesterol 629 mg/dl, LDL-Cho 1,930 mg/dl. Renal biopsy was normal on light microscopy, and immunofluorescence demonstrated no staining. Due to the risk of deterioration of diabetes by administering prednisolone, he was given Neoral at 2.0 mg/kg/day. He was also given fluvastatin (40 mg/day) for hyperlipidemia after the renal biopsy. At four weeks after the start of Neoral and fluvastatin, his nephrosis continued, but his LDL-Cho and total cholesterol decreased. At six weeks after treatment, proteinuria gradually reduced. At eight weeks after treatment, the proteinuria had disappeared. Nephrotic syndrome is often associated with abnormal lipid metabolism, and many patients with nephrotic syndrome show high levels of LDL-Cho. It has been reported recently that LDL apheresis is effective against nephrotic syndrome. However, in the present case, it can be speculated that the improvement of hyperlipidemia by fluvastatin probably augmented the effect of Neoral, presumably through the increased cellular uptake of Neoral. This suggests that fluvastatin may be considered as the treatment of choice for the disturbed lipoprotein profile in patients with nephrotic syndrome.

Topics: Anticholesteremic Agents; Cyclosporine; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Emulsions; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hyperlipidemias; Immunosuppressive Agents; Indoles; Male; Middle Aged; Nephrosis, Lipoid; Remission Induction; Treatment Outcome

Currently available data and clinical observations which suggest that there is a pathogenetic relationship between hypertension, diabetes mellitus, and atherosclerosis have provided a concept of the X syndrome, by which hypertensive patients, mainly males, have impaired insulin tolerance along with hyperinsulinemia and concurrent atherogenic disorders of lipid metabolism. The paper discussed the specific pathogenetic mechanisms, clinical manifestations, and prospects for drug correction of the metabolic syndrome. The treatment of arterial hypertension with the calcium antagonist Lomir has indicated there are no negative changes as a control of non-insulin-dependent diabetes mellitus in the presence of effective correction of arterial hypertension and atherogenic dyslipidemias. With the monotherapy of essential hypertension concurrent with hypercholesterolemia with the alpha 1-adrenoblocker Doxazosin, in addition to the agent's high antihypertensive effects, the authors noted its favourable action on lipid spectral parameters and platelet functional activity. There is abundant evidence for the use of specific hypolipidemic agents in patients with essential hypertensive refractory to current antihypertensive drugs. The data obtained with the use of Lescol (fluvastatin) in patients with hypertensive disease and hypercholesterolemia suggest that by substantially reducing the levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and its transport protein apo B does not deteriorate the quality of correction of arterial hypertension in this group of patients.

Topics: Anticholesteremic Agents; Arteriosclerosis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Doxazosin; Enzyme Inhibitors; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Indoles; Insulin Resistance; Isradipine; Lipid Metabolism; Male; Middle Aged; Syndrome