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

Elevated levels of total cholesterol and low-density lipoprotein play an important role in the development of atheromas and, therefore, in cardiovascular diseases. Cholesterol biosynthesis follows a circadian rhythm and is principally produced at night (between 12:00 am and 6:00 am). The adjustment of hypolipaemic therapy to biologic rhythms is known as chronotherapy. Chronotherapy is based on the idea that medication can have different effects depending on the hour at which it is taken. Statins are one of the most widely used drugs for the prevention of cardiovascular events. In usual clinical practice, statins are administered once per day without specifying the time when they should be taken. It is unknown whether the timing of statin administration is important for clinical outcomes.. To critically evaluate and analyse the evidence available from randomised controlled trials regarding the effects of chronotherapy on the effectiveness and safety of treating hyperlipidaemia with statins.. We searched the CENTRAL, MEDLINE, Embase, LILACS, ProQuest Health & Medical Complete, OpenSIGLE, Web of Science Conference Proceedings, and various other resources including clinical trials registers up to November 2015. We also searched the reference lists of relevant reviews for eligible studies.. We included randomised controlled trials (RCTs), enrolling people with primary or secondary hyperlipidaemia. To be included, trials must have compared any chronotherapeutic lipid-lowering regimen with statins and any other statin lipid-lowering regimen not based on chronotherapy. We considered any type and dosage of statin as eligible, as long as the control and experimental arms differed only in the timing of the administration of the same statin. Quasi-randomised studies were excluded.. We used the standard methodological procedures expected by Cochrane. We extracted the key data from studies in relation to participants, interventions, and outcomes for safety and efficacy. We calculated odds ratios (OR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Using the GRADE approach, we assessed the quality of the evidence and we used the GRADEpro Guideline Development Tool to import data from Review Manager to create 'Summary of findings' tables.. This review includes eight RCTs (767 participants analysed in morning and evening arms). The trials used different lipid-lowering regimens with statins (lovastatin: two trials; simvastatin: three trials; fluvastatin: two trials; pravastatin: one trial). All trials compared the effects between morning and evening statin administration. Trial length ranged from four to 14 weeks. We found a high risk of bias in the domain of selective reporting in three trials and in the domain of incomplete outcome data in one trial of the eight trials included. None of the studies included were judged to be at low risk of bias.None of the included RCTs reported data on cardiovascular mortality, cardiovascular morbidity, incidence of cardiovascular events, or deaths from any cause. Pooled results showed no evidence of a difference in total cholesterol (MD 4.33, 95% CI -1.36 to 10.01), 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence), low-density lipoprotein cholesterol (LDL-C) levels (MD 4.85 mg/dL, 95% CI -0.87 to 10.57, 473 participants, five trials, mean follow-up 9 weeks, low-quality evidence), high-density lipoprotein cholesterol (HDL-C) (MD 0.54, 95% CI -1.08 to 2.17, 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence) or triglycerides (MD -8.91, 95% CI -22 to 4.17, 510 participants, five trials, mean follow-up 9 weeks, low-quality evidence) between morning and evening statin administration.With regard to safety outcomes, five trials (556 participants) reported adverse events. Pooled analysis found no differences in statins adverse events between morning and evening intake (OR 0.71, 95% CI 0.44 to 1.15, 556 participants, five trials, mean follow-up 9 weeks, low-quality evidence).. Limited and low-quality evidence suggested that there were no differences between chronomodulated treatment with statins in people with hyperlipidaemia as compared to conventional treatment with statins, in terms of clinically relevant outcomes. Studies were short term and therefore did not report on our primary outcomes, cardiovascular clinical events or death. The review did not find differences in adverse events associated with statins between both regimens. Taking statins in the evening does not have an effect on the improvement of lipid levels with respect to morning administration. Further high-quality trials with longer-term follow-up are needed to confirm the results of this review.

Topics: Anticholesteremic Agents; Drug Chronotherapy; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hyperlipidemias; Indoles; Lovastatin; Pravastatin; Randomized Controlled Trials as Topic; Simvastatin

The "statins," or hydroxymethylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors, are a generally safe class of drugs that are widely used throughout the world and are rarely associated with severe hepatotoxicity. In this article, two cases of severe hepatotoxicity attributed to statin use are presented. In addition, a detailed summary of previously published cases of statin hepatotoxicity and the risks and benefits of statins in patients with chronic liver disease are presented. Drug-induced liver injury (DILI) from statins typically presents with an acute hepatocellular liver injury pattern, although mixed or cholestatic injury patterns have also been reported. Nonspecific autoantibodies as well as clinical, laboratory, and histological features of an autoimmune-like hepatitis may be present in some patients with statin hepatotoxicity. Despite their widespread use, acute liver failure and death have rarely been reported in patients with statin hepatotoxicity. Multiple retrospective studies as well as a large prospective randomized controlled trial demonstrate that statins can safely be given to hyperlipidemic patients with compensated chronic liver disease.

Topics: Adult; Aged; Aged, 80 and over; Atorvastatin; Autoimmunity; Biomarkers; Biopsy; Chemical and Drug Induced Liver Injury; Chronic Disease; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Liver; Liver Diseases; Male; Middle Aged; Practice Guidelines as Topic; Pyrroles; Risk Assessment; Treatment Outcome; Young Adult

Individuals with chronic kidney disease are at high risk for cardiovascular disease and have a high prevalence of hyperlipidemia. Lipid-lowering therapy may help patients with renal disease reduce their risk for cardiovascular events.. A pooled analysis of 30 completed clinical trials compared the efficacy and safety profiles of fluvastatin in subgroups of patients with moderate to severe renal insufficiency (creatinine clearance < 50 ml/min) and patients with normal renal function or mild renal insufficiency (creatinine clearance > or = 50 ml/min).. Changes in lipid parameters with fluvastatin treatment were similar for the compared patient subgroups. Fluvastatin treatment reduced combined cardiac death and myocardial infarction by 41% compared with placebo among patients with moderate to severe renal insufficiency (hazard ratio, 0.59; p=0.007) and by 30% among patients with normal renal function or mild renal insufficiency (hazard ratio, 0.70; p=0.009). The relative reduction in the risk of major adverse cardiac events, a composite endpoint comprising cardiac death, nonfatal myocardial infarction, and coronary intervention procedures, with fluvastatin treatment was not significant for patients with moderate to severe renal insufficiency (hazard ratio, 0.83; p=0.18); in this patient subgroup, the incidence of coronary intervention procedures was similar between treatment groups. The safety profiles were similar for fluvastatin- and placebo-treated patients.. The results of this pooled analysis indicate that fluvastatin is safe and effective for reducing cardiac death and nonfatal myocardial infarction in patients with moderate to severe renal insufficiency. Fluvastatin did not reduce the rate of coronary intervention procedures.

Topics: Anticholesteremic Agents; Cholesterol, LDL; Comorbidity; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Incidence; Indoles; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Risk Factors; Survival Analysis; Treatment Outcome

Premature atherosclerotic coronary heart disease driven by multiple risk factors is a major cause of morbidity and mortality among the 6 million patients in the United States with chronic renal failure. Consensus is that kidney failure and renal transplantation patients should be treated aggressively for dyslipidemia. Major medical literature databases were searched for published information about fluvastatin, a HMG-CoA reductase inhibitor, used in patients with impaired renal function. This article characterizes the dyslipidemia observed in these clinical settings and reviews the clinical experience with fluvastatin.

Topics: Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Lipids; Treatment Outcome

A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased international normalized ratio (INR) without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient's goal INR. The literature supports a drug interaction between warfarin and fluvastatin due to the strong affinity of fluvastatin for the cytochrome P450 enzyme 2D6. This interaction has not been seen with atorvastatin. Lovastatin also reportedly has caused increases in INR when coadministered with warfarin. It is unclear whether simvastatin interacts with warfarin, but it may increase INRs slightly or increase serum simvastatin levels. One case report describes an interaction between simvastatin and the anticoagulant acenocoumarol, which resulted in an elevated INR. Pravastatin does not appear to interact with warfarin but has caused an increased INR when combined with the anticoagulant fluindione. Thus, until more definitive data are available, clinicians should monitor the INR closely after starting statin therapy in any patient receiving anticoagulation therapy.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atorvastatin; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; International Normalized Ratio; Male; Patient Compliance; Pyrroles; Simvastatin; Venous Thrombosis; Warfarin

Coronary heart disease (CHD), the result of coronary atherosclerosis, is the largest single killer of Americans. Central to the pathogenesis of atherosclerosis are the deposition and retention of cholesterol in the arterial walls. Lipid modification, therefore, is key to CHD prevention.. Data from trials evaluating the safety and efficacy of several pharmacologic agents for dyslipidemia were thoroughly reviewed.. Agents such as bile acid sequestrants, fibric acids, and nicotinic acid have a role in treating dyslipidemia. However, statins are the safest and most effective of the lipid-modifying drugs, reducing the incidence of CHD by as much as 21% to 43%. Despite the overall safety and efficacy of these agents, many patients undergoing statin therapy fail to achieve the treatment goals specified in the National Cholesterol Education Program Adult Treatment Panel III guidelines, often because of suboptimal use, tolerability problems, or lack of compliance. Although adverse effects of statins are generally mild and transient, more serious adverse effects, including myotoxicity, liver toxicity, and rhabdomyolysis, are still possible with statin monotherapy and are more common in patients receiving concomitant therapy with other drugs metabolized by the cytochrome P-450 enzyme system.. Because of the overall safety and efficacy of the statins, more patients with or at risk for CHD should be receiving aggressive therapy to lower low-density lipoprotein cholesterol levels and reduce CHD risk.

Topics: Atorvastatin; Cholesterol; Cholesterol, HDL; Coronary Disease; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hyperlipidemias; Indoles; Lovastatin; Pravastatin; Pyrroles; Randomized Controlled Trials as Topic; Risk Assessment; Simvastatin; Stroke; Triglycerides; United States

In the prevention of coronary heart disease the aim to achieve the target cholesterol and triglyceride levels and the maximal risk reduction leads to the combination of lipid lowering agents. The importance of the combination is supported by the fact that in monotherapy use of the high dose of the drugs, the lipid lowering effect is modest and the side effects are more frequent. The combined therapy is expected to be used more frequently despite the fact, that the improperly applied combination could have serious unfavourable effects. The authors review the advantages and drawbacks of the fibrate-statin combination, which could be used in the most frequent lipid abnormality, the high cholesterol and high triglyceride level, when the combination of micronized fenofibrate and fluvastatin is recommended. Beside the co-administration of other lipid lowering drugs (nicotine acid and resins), it is discussed the combination of statins and fibrates with a new, cholesterol absorption inhibitor, ezetimibe, a well tolerated drug with advantageous safety profile. Considering further metabolic risks the combination of lipid lowering drugs with glitazones, hormone replacement therapy, homocysteine reducing agents is as well highlighted.

Topics: Anticholesteremic Agents; Apolipoproteins; Azetidines; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Drug Therapy, Combination; Ezetimibe; Fatty Acids, Monounsaturated; Fenofibrate; Fluvastatin; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipids; Pravastatin; Simvastatin; Triglycerides; Vitamin B 12; Vitamin B 6

Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary artery disease (CAD) in all patients. However, these agents are more cost-effective in high-risk patients whose absolute risk of CAD is greater than that of low-risk patients. Furthermore, from preliminary data, it appears that there is greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels (ie, lower is better). The identification and aggressive treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the Adult Treatment Panel (ATP) III of the US National Cholesterol Education Program (NCEP), emphasize that patients with CAD, diabetes, or global risk of CAD >20% over 10 years and LDL-C levels >130 mg/dL should receive drug therapy with a goal of reducing LDL-C levels to <100 mg/dL. The recent results of the United Kingdom's Heart Protection Study (HPS) strongly suggest that even those with CAD or who are at high risk and LDL-C levels >100 mg/dL would benefit from drug therapy. Although optimal LDL-C levels have been set at <100 mg/dL for high-risk patients, recent studies show only about 20% of such patients meet these goals. Thus, a large treatment gap remains that needs to be overcome if we are to continue to make significant inroads into preventing further morbidity and mortality in these high-risk subjects. Of therapeutic options available currently and for the near future, statins remain the most effective and well-tolerated form of lipid-lowering therapy. Other therapies include bile acid sequestrants, niacin, and plant stanols. However, none of these is, in general, sufficiently effective as an initial agent to achieve these more aggressive LDL-C goals in the high-risk patient. However, combination therapy with a statin and 1 of these other lipid-lowering agents is useful in patients who are unable to achieve lipid goals on monotherapy. A number of agents for reducing LDL-C levels currently in development may be available in the near future, including 2 new statins: pitavastatin and rosuvastatin. Rosuvastatin, which is in the later stages of the US Food and Drug Administration (FDA) approval process, has been shown to produce significantly greater reductions in LDL-C levels compared with atorvastatin, simvastatin, and pravastatin, and allows more patients to meet lipid goals. Ezetimibe, the first of an entirely new class of LDL-C-l

Topics: Adult; Anticholesteremic Agents; Atorvastatin; Bile Acids and Salts; Cholesterol, LDL; Clinical Trials as Topic; Coronary Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lovastatin; Niacin; Practice Guidelines as Topic; Pravastatin; Pyrimidines; Pyrroles; Risk; Rosuvastatin Calcium; Simvastatin; Sulfonamides; Treatment Outcome; United States

In England, only 30% of patients with established coronary heart disease (CHD) and raised serum lipids, and fewer than 4% of individuals eligible for primary prevention, receive lipid-lowering therapy. Target total cholesterol concentrations are achieved in fewer than 50% of patients who do receive such treatment. Here, we review the use of statin therapy in the prevention of CHD events.

Topics: Anticholesteremic Agents; Atorvastatin; Coronary Disease; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hyperlipidemias; Indoles; Patient Selection; Pravastatin; Pyridines; Pyrroles; Risk Factors; Simvastatin; Treatment Outcome

Fluvastatin is an HMG-CoA reductase inhibitor used to treat patients with hypercholesterolaemia. Since fluvastatin was last reviewed in Drugs, trials have shown its efficacy in the secondary prevention of coronary heart disease (CHD) events and death and have expanded knowledge of its effects in primary CHD prevention and its mechanisms of activity. In addition to reducing total (TC) and low density lipoprotein (LDL-C) cholesterol, fluvastatin has antiatherogenic, antithrombotic and antioxidant effects, can improve vascular function, and may have immunomodulatory effects. Although fluvastatin interacts with bile acid sequestrants (requiring separation of doses), its pharmacokinetics permit oral administration to most patient groups. Fluvastatin is well tolerated, with adverse effects usually mild and transient. Use of fluvastatin to reduce lipids in patients with primary hypercholesterolaemia is well established. Its effects are similar in most patient groups, with 20 to 80 mg/day reducing LDL-C by 22 to 36%, triglycerides (TG) by 12 to 18% and apolipoprotein B by 19 to 28% and increasing high density lipoprotein cholesterol by 3.3 to 5.6%. Attempts to find fluvastatin dosages with efficacy equivalent to that of other HMG-CoA reductase inhibitors produce variable results, but larger per-milligram fluvastatin dosages are needed when patients switch from other HMG-CoA reductase inhibitors. Combinations of fluvastatin with fibric acid derivatives and bile acid sequestrants produce additive effects. Small noncomparative studies suggest fluvastatin reduces LDL-C in patients with hypercholesterolaemia secondary to kidney disorders by < or = 40.5% and with type 2 diabetes mellitus by < or = 32%. Three large randomised, double-blind trials show fluvastatin can help prevent CHD events or death and slow disease progression in patients with CHD with or without hypercholesterolaemia. In the Fluvastatin Angiographic Restenosis trial in patients undergoing balloon angioplasty, fluvastatin 80 mg/day for 40 weeks reduced the postangioplasty rate of deaths plus myocardial infarctions (1.5% vs 4% with placebo, p < 0.025) without altering vessel luminal diameters. In the Lipoprotein and Coronary Atherosclerosis Study in patients with coronary artery stenosis, luminal diameter reduced to a significantly lesser extent after fluvastatin 20 mg twice daily than placebo after 2.5 years (-0.028 vs -0.01 mm, p < 0.005). The Lescol in Symptomatic Angina study found reductions in all. An evolving pattern of data suggests that, in addition to its well established efficacy and cost effectiveness in reducing hypercholesterolaemia, fluvastatin may now also be considered for use in the secondary prevention of CHD.

Topics: Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Indoles; Randomized Controlled Trials as Topic

Statins act by competitive inhibition of HMG-CoA reductase, a key enzyme regulating cholesterol synthesis. Reduction in serum LDL, the crucial biological expression dependent on this mechanism, varies in intensity as a function of the type and of the dose of statin.. Besides their lipid lowering effect, statins have also been demonstrated to have pleiotropic effects mostly directly related to HMG-CoA reductase inhibition.. Several clinical studies investigating prevention of cardiovascular disease have established that statins decrease cardiovascular morbidity and mortality. Results have been very coherent for both primary and secondary prevention with statins. The cardiovascular benefit is most likely partly related to its pleiotropic effects, particularly those inducing a stabilization of the atheromatous plaques.. Interventional studies have clearly established the role of statins in comparison with other lipid lowering agents for the prevention of cardiovascular events in most situations although a few therapeutic choices remain a subject of debate. Globally, the primary indications of statins are hypercholesterolemia and mixed hyperlipidemia with moderately elevated triglycerides. There are still some questions concerning the therapeutic goals of statin therapy.

Topics: Anticholesteremic Agents; Atorvastatin; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lovastatin; Pravastatin; Pyridines; Pyrroles; Simvastatin

Cardiovascular disease remains a significant cause of morbidity and mortality in patients who have undergone renal transplantation, with one of the main risk factors being post-transplantation hyperlipidaemia. To date, however, optimal management of elevated lipid levels in such patients has been hindered by the lack of both effective and safe treatments, coupled with concerns over probable interactions with immunosuppressive therapy, particularly cyclosporin. Numerous studies confirm that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, such as fluvastatin, are effective lipid-lowering agents in renal transplant recipients, supporting findings in other patients' groups. Moreover, based on investigations of metabolic profile and clinical observation, fluvastatin (at dosages of up to 80 mg/day) is well tolerated in renal transplant recipients receiving cyclosporin. In clinical trials to date, no instances of rhabdomyolysis have been observed during co-administration of fluvastatin and cyclosporin. The potential of fluvastatin for improving survival in renal transplant recipients, in terms of both cardiovascular mortality and graft rejection, is currently being investigated in two ongoing studies: ALERT (Assessment of Lescol [fluvastatin] in Renal Transplantation) and SOLAR (Study of Lescol [fluvastatin] in Acute Rejection). The results of these landmark studies should confirm the safe utility of fluvastatin in the renal transplantation setting.

Topics: Anticholesteremic Agents; Clinical Trials as Topic; Contraindications; Cyclosporine; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Immunosuppressive Agents; Indoles; Kidney Transplantation

Luminal renarrowing (restenosis) is the major limitation of percutaneous transluminal coronary angioplasty (PTCA), and the search for a 'magic bullet' to prevent this apparent biological healing response to vessel injury has thus far been unsuccessful. Large clinical trials using serial quantitative coronary angiography have, however, provided some valuable insight into this area. In particular, the restenosis process may be measured as the loss in minimal luminal diameter from post-PTCA to follow-up angiography, and is essentially ubiquitous and normally distributed. The angiographic outcome of clinical trials can thus be appropriately evaluated using a continuous rather than a categorical approach, which also considerably reduces the number of patients required. Fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown experimentally to reduce the neointimal proliferative response after PTCA, independent of its lipid-lowering action. The FLuvastatin Angioplasty REstenosis trial was designed to evaluate whether fluvastatin 40 mg twice daily, commencing at least 2 weeks before planned PTCA, can reduce luminal loss by 30% from successful PTCA to follow-up angiography at 26 +/- 2 weeks in 730 evaluable patients.

Topics: Angioplasty, Balloon, Coronary; Coronary Disease; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Randomized Controlled Trials as Topic; Recurrence; Research Design

Topics: Anticholesteremic Agents; Cardiovascular System; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipoproteins; Lovastatin; Pravastatin; Simvastatin

To assess the efficacy and safety of fluvastatin sodium extended-release tablets (fluvastatin XL) 80 mg once daily compared to fluvastatin sodium immediate-release capsules (fluvastatin IR) 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk.. In this multi-center, randomized, double-blind, double-dummy, active-controlled, parallel-group study, after 6-week open-label treatment with fluvastatin IR 40 mg once daily, patients who did not reach their lipid goals were randomized to 12-week double-blind treatment with fluvastatin XL 80 mg once daily or fluvastatin IR 40 mg twice daily.. (1) There were 218 patients enrolled in each group. At the study endpoint, no statistical difference was found in the mean percent change from baseline for LDL-C with -8.69% [from (3.504 ± 0.060) mmol/L to (3.153 ± 0.065) mmol/L] in the fluvastatin XL group and -7.89% [from (3.491 ± 0.050) mmol/L to (3.181 ± 0.060) mmol/L] in the fluvastatin IR group (P > 0.05). The 95%CI for difference between the two groups in adjusted mean percent change from baseline was (-4.70%-3.09%), which was within the pre-specified non-inferiority margin. In the fluvastatin XL group, the proportion of patients with moderate cardiovascular (CV) risk and high CV risk achieving their LDL-C treatment goals at endpoint was 50.0% and 31.5% respectively, while the proportion was 42.5% and 24.5% respectively in the fluvastatin IR group. No significant difference was found between the two groups in the proportion of patients who reached their lipid goals and the changes from baseline with other lipid parameters. (2) Similar safety profiles were observed in the two treatment groups, with 21.1% adverse event (AE) (8.3% study-drug related AE) in the fluvastatin XL group and 17.0% AE (6.3% study-drug related AE) in the fluvastatin IR group.. The efficacy of fluvastatin XL 80 mg once daily is comparable to fluvastatin IR 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk and both treatments are safe and well-tolerated.

Topics: Cardiovascular Diseases; Double-Blind Method; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Indoles; Lipids; Risk Factors; Tablets

Statins are recommended in heart transplantation regardless of lipid levels. However, it remains unknown whether dosing should be maximized or adjusted toward a pre-defined cholesterol threshold.. This pilot, randomized, open-label study compares an early maximal dose of fluvastatin (80 mg/day) with a strategy based on 20 mg/day subsequently titrated to target low-density lipoproteins (LDL) <100 mg/dl. Efficacy outcomes consisted of achieving an LDL level of <100 mg/dl at 12 months after transplant, and change in intracoronary ultrasound parameters.. Fifty-two patients were randomized. Overall safety, and efficacy in achieving LDL targets (13 [50%] vs 14 [54%]; p = 0.8) were comparable between study arms, but 17 (65%) patients needed a dose increase in the titrated-dosing arm. Early LDL levels and average LDL burden were lower in the maximal-dosing arm (p < 0.05). Few patients developed an increase in maximal intimal thickness of >0.5 mm, with numerical prevalence in the titrated-dosing arm (3 [12.5%] vs 1 [5%]; p = 0.3). Intimal volume increased in the titrated-dosing (p < 0.01) but not in the maximal-dosing arm (p = 0.1), which accordingly showed a higher prevalence of negative remodeling (p = 0.02).. Despite being as effective as the titrated-dosing approach in achieving LDL <100 mg/dl at 12 months after transplant, the maximal-dose approach was associated with a more rapid effect and with potential advantages in preventing pathologic changes in graft coronary arteries.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol; Coronary Vessels; Creatine Kinase; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Heart Transplantation; Humans; Hyperlipidemias; Indoles; Lipoproteins, LDL; Male; Middle Aged; Pilot Projects; Retrospective Studies; Treatment Outcome; Ultrasonography, Interventional; Vascular Diseases

Postprandial lipemia is known to exert a reversible detrimental effect on endothelium-dependent flow-mediated vasodilation (FMD). Fasting FMD has shown to be improved by fluvastatin. In this study, we investigated whether lipemia-induced endothelial dysfunction can be mitigated by fluvastatin in two (immediate-release and extended-release) formulations.. In 27 patients with the metabolic syndrome, randomized in a three-period crossover design for 5 weeks each to 80 mg extended-release fluvastatin daily, 40 mg immediate-release fluvastatin twice daily (b.i.d.) or placebo, the fasting and postprandial lipids and FMD of the brachial artery were measured at baseline and after 5 weeks of each treatment period. Postprandial lipemia was induced by administration of whipping cream containing 33% fat (1 g fat/kg body weight). FMD was determined by two-dimensional ultrasonography of the brachial artery in the fasting state and 4 h after the fatty meal. Lipids were determined using routine methods.. Fasting triglycerides were reduced after immediate-release and extended-release fluvastatin by 16 and 23%, respectively, and postprandial triglycerides by 20 and 29%, respectively. The fasting FMD was also improved by each treatment. The postprandial FMD impairment, however, was mitigated only after 40 mg b.i.d. After 80 mg fluvastatin, the last dose of which had been administered the previous evening, the lipemic FMD impairment was the same as after the placebo.. Fluvastatin improves fasting FMD regardless of whether it is administered as 40 mg b.i.d. or 80 mg daily given in the evening. The lipemic FMD impairment, in contrast, is improved only by 40 mg b.i.d. when the tablet is taken in the morning of the test day. As the half-life of fluvastatin is about 2 h, we surmise that an improvement occurs only when sufficient amounts of fluvastatin are present in the bloodstream.

Topics: Administration, Oral; Aged; Brachial Artery; Capsules; Chemistry, Pharmaceutical; Cross-Over Studies; Delayed-Action Preparations; Dietary Fats; Double-Blind Method; Drug Administration Schedule; Endothelium, Vascular; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Metabolic Syndrome; Middle Aged; Postprandial Period; Regional Blood Flow; Tablets; Time Factors; Treatment Outcome; Triglycerides; Ultrasonography; Vasodilation

Nephrotic dyslipidemia is a risk factor for development of systemic atherosclerosis; also it may aggravate glomerulosclerosis and enhance progression of glomerular disease. We aimed to assess the efficacy and safety of Monascus purpureus Went rice vs. fluvastatin therapy in the management of nephrotic dyslipidemia.. Seventy-two patients with idiopathic persistent nephrotic syndrome with secondary dyslipidemia were included. They were randomly allocated into 3 - age and sex - matched groups. The first group comprised of 20 cases and were given Monascus purpureus Went rice, second group comprised 30 cases were given fluvastatin. The remaining 22 received no anti-dyslipidemic therapy and constituted a control group. All of these patients were subjected to thorough laboratory investigations including renal function tests, lipogram and neurological assessment.. Our results showed that both fluvastatin and Monascus purpureus Went rice were well-tolerated with no significant side effects. Both of them significantly reduced cholesterol after 6 months and 1 year. In comparison to baseline values, fluvastatin achieved a significant and progressive reduction of serum cholesterol by 35%, 38% and 42% at 3 months, 6 months and after 1 year respectively (p<0.001). Similar reductions were observed in the Monascus purpureus Went rice group. After one year we observed that serum cholesterol was significantly lower in statin and Monascus purpureus Went rice groups compared to the control group.. Monascus purpureus Went rice is safe, effective cholesterol lowering agent for nephrotic dyslipidemia both in adults and children.

Topics: Adolescent; Adult; Anticholesteremic Agents; Atherosclerosis; Child; Drugs, Chinese Herbal; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Male; Monascus; Nephrotic Syndrome; Pilot Projects; Risk Factors; Young Adult

Nephrotic dyslipidemia is a risk factor for the development of systemic atherosclerosis; it may also aggravate glomerulosclerosis and enhance the progression of glomerular disease. We aimed to assess the efficacy and safety of Monascus purpureus Went rice versus fluvastatin therapy in the management of nephrotic dyslipidemia.. In total 72 patients with idiopathic persistent NS with secondary dyslipidemia were included. They were randomly allocated into three age- and sex-matched groups. The first group comprised 20 cases that were given M. purpureus Went rice in a dose of 600 mg twice per day for one month and then once daily. The second group comprised 30 cases that were given fluvastatin in a daily dose of 20 mg. The remaining 22 received no antidyslipidemic therapy and constituted a control group. All of these patients were subjected to thorough laboratory investigations, including renal function tests and lipograms. Moreover, neuromuscular status was evaluated with electromyography and nerve conduction velocity.. Our results showed that both fluvastatin and M. purpureus Went rice were well-tolerated with no evidence of significant side effects, including on neuromuscular function. Both M. purpureus Went rice and fluvastatin significantly reduced cholesterol after six months and one year, respectively.. Monascus purpureus Went rice is a safe, effective and economic treatment strategy for nephrotic dyslipidemia.

Topics: Adolescent; Adult; Anticholesteremic Agents; Child; Dose-Response Relationship, Drug; Electromyography; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Male; Medicine, Chinese Traditional; Monascus; Muscle, Skeletal; Nephrotic Syndrome; Phytotherapy; Plant Preparations; Prospective Studies; Treatment Outcome

The present study was designed to test the hypothesis that fluvastatin might improve arterial stiffness, as assessed with pulse wave velocity (PWV), in patients with coronary artery disease (CAD) and hyperlipidemia over the long term.. Ninety-three patients were randomly assigned to either fluvastatin (group A, n=50) or bezafibrate (group B, n=43) and followed for 5 years. There was no difference in the clinical findings between the 2 groups. In group A, there was a progressive reduction in the brachial-ankle PWV along with a decrease in serum low-density lipoprotein-cholesterol (LDL-C) and C-reactive protein (CRP) by 12 months after fluvastatin, and the improvement was maintained until 5 years after treatment. In group B, despite identical lowering of the serum lipid, PWV was progressively increased. In group A, the percentage change in PWV correlated significantly with that of the serum CRP (r=0.49, p<0.001), but not with that of the serum LDL-C after treatment.. The beneficial vascular effects of fluvastatin persisted for a long period in patients with CAD and hyperlipidemia. Its anti-inflammatory action might contribute to the favorable effects on arterial stiffness.

Topics: Aged; Aorta; Bezafibrate; Blood Flow Velocity; Coronary Artery Disease; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Indoles; Linear Models; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Pulsatile Flow; Risk Factors; Treatment Outcome

The objective of the study was to evaluate potential benefits of docosahexaenoic acid (DHA) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia. A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides (averaging 2.2 mmol/L) were randomised to take 4 g/day (n = 15) or 8 g/day (n = 15) of tuna oil or olive oil (placebo, n = 15) for 6 months. Plasma lipids, blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial. Plasma triglycerides were reduced 27% by 8 g/day DHA-rich fish oil (P < 0.05) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months. Even though total cholesterol was already well controlled by the statin treatment (mean initial level 4.5 mmol/L), there was a further dose-dependent reduction with fish oil supplementation (r = -0.344, P < 0.05). The extent of total cholesterol reduction correlated (r = -0.44) with the initial total cholesterol levels (P < 0.005). In the subset with initial plasma cholesterol above 3.8 mmol/L, plasma very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated and assayed for cholesterol and apolipoprotein B (apoB) at the commencement of the trial and at 3 months of intervention. Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL. There were no changes in IDL cholesterol, IDL apoB and high-density lipoprotein cholesterol. The results demonstrate that DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months. Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia.

Topics: Animals; Apolipoproteins B; Atorvastatin; Cholesterol, LDL; Dietary Fats; Dietary Fats, Unsaturated; Dietary Supplements; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Female; Fish Oils; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipid Metabolism; Lipids; Lipoproteins, IDL; Lipoproteins, VLDL; Male; Middle Aged; Pyridines; Pyrroles; Simvastatin; Treatment Outcome; Triglycerides

Statins inhibit the rate-limiting step in cholesterol biosynthesis, the conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate by HMG-CoA reductase. Statins are usually taken in the evening as the HMG-CoA reductase activity is high during the night. This recommendation might not apply if statins are given as extended-release (ER) formulations. The present study investigated the influence of time of intake of fluvastatin 80 mg ER on cholesterol biosynthesis. Main objectives were to measure the change in 24-hour urinary mevalonic acid excretion, to determine plasma concentrations of mevalonic acid and fluvastatin and to monitor triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol.. This was a randomized, 2-period crossover study in 26 hypercholesterolemic patients who received a single daily dose of fluvastatin both in the morning and in the evening.. At baseline, the amount of mevalonic acid was 204.9 +/- 68.1 microg/g creatinine. After a single dose of fluvastatin mean urine values of mevalonate were significantly reduced to 129.8 +/- 66.2 micro/g (evening) and to 118.7 +/-34.3 microg/g (morning; n.s. between groups), thus representing a reduction of about 39%. Compared to baseline, plasma mevalonate concentrations were decreased by fluvastatin resulting in similar 24-hour profiles after the morning and the evening dosage. The pharmacokinetics of fluvastatin were similar in both periods of the study, with higher plasma concentrations for several hours following the evening dosage.. This study demonstrates that fluvastatin ER is equally effective in inhibiting cholesterol biosynthesis when given once daily in the morning and once daily in the evening.

Topics: Adult; Biomarkers; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Delayed-Action Preparations; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Mevalonic Acid; Middle Aged; Time Factors; Triglycerides

The aim of the study was to estimate the effects of 4-weeks therapy of fluvastatin extended release (XL) on lipids serum, C-reactive protein (CRP), erythrocyte structure membrane (thiobarbituric acid reactive substances--TBARS concentrations, membrane cholesterol and the activity of Na+K(+)-ATPase in erythrocytes) in patients with hyperlipidemia without any clinical signs of atherosclerosis.. The study comprised 37 persons, including 15 healthy volunteers and 22 patients with hyperlipidemia (TC > 200 mg/dl, LDL-C > 130 mg/dl, TG < 400 mg/dl) treated with fluvastatin XL 80 mg/d. Before and after 4 weeks of active treatment the following parameters were determined: lipids (by enzymatic method using BioMerieux tests), CRP (by immunoturbidimetric method), TBARS concentrations (by method of Stock and Dormandy), membrane cholesterol (method of Ilcy), Na+K(+)-ATPase activity (method of Bartosz et al.).. It was noticed significantly higher concentrations of CRP, TBARS, membrane cholesterol and lower activity of Na+K(+)-ATPase in erythrocytes of patients with hyperlipidemia than in the control group. Fluvastatin XL caused a significant decrease in serum TC (by 18%), LDL-C (by 24%), TG (by 16%), CRP (by 23%) and TBARS (by 31%), membrane cholesterol (by 30%) in comparison to the initial values before active therapy. The activity of Na+K(+)-ATPase didn't significantly change. The mean values of CRP, TBARS, membrane cholesterol level after active treatment are still higher than in the control group.. The short-term treatment of fluvastatin extended release wasn't enough efficient to compensate disorders in erythrocyte membrane structure of patients with hyperlipidemia.

Topics: Adult; Anticholesteremic Agents; C-Reactive Protein; Delayed-Action Preparations; Erythrocyte Membrane; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Lipid Metabolism; Male; Middle Aged; Reference Values; Treatment Outcome

Recent experimental and clinical data suggest that lowering serum lipid levels with statins may prevent or delay the process of restenosis. The purpose of this trial is to determine whether lipid levels relate to restenosis and/or whether statin therapy can prevent or delay the process of restenosis after intracoronary stenting.. One hundred thirty-six patients who underwent single coronary artery stenting from June 1995 to June 1997 in our institution were included in the study. All these patients were followed for at least 9 months (mean 392+/-148 days) for major adverse cardiac events (MACE). We defined as MACE the occurrence of death, myocardial infarction, or need for target lesion revascularization. From this cohort, 103 patients had at least one lipid parameter from the lipid profile evaluated within 2 months from the date of the procedure. Patients who had the stent because of an acute myocardial infarction were included in the study only if their lipid profile was evaluated before or at least 6 weeks after the event. Patients with triglyceride levels above 500 had both triglyceride and low-density lipoprotein cholesterol levels excluded from the statistical analysis. Patients were divided into two groups based on lipid levels: normal (Group I; n=31) and elevated (Group II; n=72). Patient outcomes were also analyzed by statin therapy use.. There was no significant difference in MACE rates between the two groups when outcomes were analyzed by lipid levels (22.6% versus 20.8% P=0.8). Furthermore, outcomes were analyzed by use of statin therapy (Group III, n=53, on statin versus Group IV, n=50, on no statin). There was also no difference in MACE rates between the two groups (20.8% versus 22%; P=0.8).. The process of restenosis has unique features that differentiate it from atherosclerosis. Although lipid-lowering therapy is crucial in delaying the process of atherosclerosis, its role in the prevention of restenosis is yet to be proven.

Topics: Aged; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Restenosis; Coronary Vessels; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipids; Male; Middle Aged; Stents; Triglycerides

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

There are few reports on the safety and efficacy of long-term treatment with statins in patients with chronic renal disease and hyperlipidemia. We evaluated these subjects treated with fluvastatin.. After a 4-week run-in period, a total of 80 patients with diabetic nephropathy or chronic glomerulonephritis were randomly allocated to receive dietary therapy and fluvastatin 20 mg/day (n=39), or dietary therapy alone (n=41) for a period of 48 weeks. Lipid parameters, rhabdomyolysis-related indicators, 24-hour urinary albumin excretion and creatinine clearance were measured. The pharmacokinetics of fluvastatin was examined in 8 patients.. Creatinine clearance and 24-hour urinary albumin excretion did not differ between the two groups. The peak serum fluvastatin concentration (Cmax) was 141+/-67 microg/L and the mean AUC0-6 h was 341+/-149 microgh/L. Fluvastatin treatment significantly lowered serum total cholesterol, low-density lipoprotein (LDL) cholesterol and apo-lipoprotein B concentrations by 16%, 25%, and 22%, respectively, compared with patients receiving dietary therapy alone. There were no significant differences in serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations between the two treatment groups. Serum creatine kinase and aldolase concentrations did not change throughout treatment in both groups.. Fluvastatin treatment significantly improved lipid parameters in patients with chronic renal disease. Fluvastatin was well tolerated, with no adverse effects on renal function and no muscular toxicity. However, the drug showed no direct renoprotective effects.

Topics: Adult; Aged; Albuminuria; Chronic Disease; Creatinine; Diabetic Nephropathies; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Middle Aged; Myoglobin; Prospective Studies

Renal transplant recipients are at increased risk of atherosclerotic vascular disease with hyperlipidemia. Many recipients have preexisting cardiovascular disease at the time of transplantation, and immunosuppressive therapy may aggravate existing risk factors or promote development of new risk factors, notably hyperlipidemia and hypertension. Fluvastatin is one of the statins, an HMG-CoA reductase inhibitor, which has been shown to be effective in lowering cholesterol levels. We treated hyperlipidemia after renal transplantation with Fluvastatin for more than 6 months. We attempted to clarify the efficacy of fluvastatin on hyperlipidemia in renal transplant recipients.. Forty-five renal transplant recipients with hyperlipidemia were enrolled in this study. The mean age was 44.2 years, with 23 men and 22 women. Thirty-seven transplantations were from a living related donors and eight from cadaveric donors. Thirty-three recipients were ABO-compatible, seven recipients had minor mismatches, and five recipients were ABO-incompatible. The dose of fluvastatin was 20 mg per day. Levels of total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), serum creatinine (s-Cr), ALT, ALP, uric acid (UA), hematocrit (Ht), CPK, and blood pressure were examined in all recipients before treatment as well as 1, 3, and 6 months after Fluvastatin administration.. The mean levels of TC and TG were significantly reduced from 256, to 224 and 215 mg/dL, and from 188 to 170 and 147 mg/dL at 1 and 6 months after treatment, respectively. The mean levels of HDL-C were 72 mg/dL before treatment, 81 mg/dL at 1 month, and 80 mg/dL at 6 months after treatment. The mean levels of LDL-C were 153 mg/dL before treatment, 145 mg/dL at 1 month, and 145 mg/dL at 6 months after treatment. Fluvastatin significantly produced a reduction rate in TC of 16%, TG of 22%, and LDL-C of 5% after 6 months of treatment, respectively. The mean levels of HDL-C of were increased 10% after 6 months of treatment. The serum creatinine and CPK were not significantly different. There were no clinically significant differences in other factors. No significant adverse effects were observed.. Fluvastatin seemed to be safe and highly effective to control TC, TG, LDL-C, and HDL-C in renal transplant recipients.

Topics: Adult; Anticholesteremic Agents; Blood Pressure; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Triglycerides

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

Thrombin activatable fibrinolysis inhibitor (TAFI) is a glycoprotein, linking coagulation and fibrinolysis. Recently, attention has been drawn to the beneficial effects of statins on haemostasis in kidney patients prone to dyslipidaemia and with a high risk of cardiovascular death. The purpose of this study was to assess whether fluvastatin affects TAFI concentration in renal transplant recipients. We evaluated thrombin-antithrombin (TAT) complexes, prothrombin fragments 1+2, thrombomodulin, plasmin-antiplasmin (PAP) complexes, TAFI, P-selectin, and lipoprotein (a), 1, 2, and 3 months before and after fluvastatin treatment and in normolipaemic kidney transplant recipients and healthy volunteers. Cholesterol and LDL fell significantly as soon as 1 month after treatment had begun and remained lowered during the therapy. TAFI and prothrombin fragments 1+2 decreased significantly after 3 months of fluvastatin administration, whereas P-selectin decreased significantly after 2 months and remained significantly lower after 3 months of this therapy. We can conclude that fluvastatin is an effective hypolipaemic agent that favourably affects haemostasis.

Topics: Adult; Antithrombin III; Carboxypeptidase B2; Fatty Acids, Monounsaturated; Female; Fibrinolysin; Fluvastatin; Hemostasis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Transplantation; Lipids; Male; Middle Aged; P-Selectin; Peptide Fragments; Peptide Hydrolases; Protein Precursors; Prothrombin

The effect of fluvastatin and fenofibrate on O2-generation by neutrophils and MDA concentration in mixed hyperlipidaemic patients with stable angina was studied. Thirty-five patients (13 men and 22 women aged 40-77 years) were randomly divided into two groups. Group I comprised 20 patients who were administered fluvastatin 40 mg once daily at bedtime for 30 days. Group II consisted of 15 patients who were administered fenofibrate 200 mg once daily at bedtime for 30 days. The control group comprised 11 clinically healthy persons, aged 21-54 years. Neutrophil O2-generation was measured using Bellavite et al. method and MDA concentrations in plasma and erythrocytes were determined by Placer et al. method. It was shown that fluvastatin had no significant effect on O2-generation while fenofibrate increased its generation. None of the examined drugs caused changes of MDA concentrations in plasma and erythrocytes.

Topics: Adult; Aged; Anticholesteremic Agents; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fluvastatin; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Reactive Oxygen Species

The effect of fluvastatin and fenofibrate on antioxidative enzymatic activity in patients with stable angina and mixed hyperlipidaemia was investigated. Thirty-five patients (13 men and 22 women) aged 40-77 years, were randomly divided into two groups. The first group comprised 20 patients who were administered fluvastatin 40 mg once daily at bedtime for 30 days. The second group consisted of 15 patients who were administered fenofibrate 200 mg once daily at bedtime for 30 days. The control group comprised 11 clinically healthy persons aged 21-54 years. The activities of SOD-1, CAT and GSH-Px in erythrocytes were measured. Fluvastatin induced an increase of the activities of all investigated enzymes. Fenofibrate caused no change of enzyme activities in patients with dyslipidaemia.

Topics: Adult; Aged; Anticholesteremic Agents; Antioxidants; Catalase; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fluvastatin; Glutathione Peroxidase; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Male; Middle Aged; Superoxide Dismutase

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

Statins have multiple actions, independent of their classical effects on lipoproteins. The data about the effects of statins on insulin resistance is controversial. This study was designed to search the statin effects on nondiabetic dyslipidemic patients. Thirty-five (17 male, 18 female) consecutive dyslipidemic patients 54.25 +/- 8.81 yr were enrolled in the study. After a standard follow-up period of lifestyle modification, the patients were given fluvastatin 40 mg/d for 8 wk. Serum analyses were done both before and after treatment. Insulin resistance was assessed by homeostasis assessment model (HOMA). Fasting plasma triglyceride, total and LDL cholesterol, fasting insulin, and HOMA index were significantly reduced and HDL cholesterol was improved after fluvastatin treatment. HOMA-IR was not correlated with triglycerides, LDL, HDL, or total cholesterol levels. The same situation was present for both fasting plasma insulin and fasting plasma glucose levels. Also age was not associated with HOMA-IR and fasting plasma insulin levels. As a conclusion, the present study indicates that fluvastatin treatment improves insulin resistance in dyslipidemic patients who do not have diabetes or impaired fasting glucose. Also, the effect of fluvastatin on insulin resistance is not associated with the lowering of triglycerides. The latter finding indicates that the effect of statins on insulin sensitivity may not be related with the lowering of triglycerides in dyslipidemic patients.

Topics: Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Insulin; Insulin Resistance; Male; Middle Aged; Treatment Outcome; Triglycerides

In this study 43 patients with idiopathic nephrotic syndrome were randomly distributed into 2 age- and sex-matched groups. The first group was given fluvastatin while the second was used as control. The cases in the 2 groups were evaluated clinically, biochemically (creatinine clearance, albumin, 24-hour proteinuria, and lipogram), neurologically, and histopathologically (examination of renal biopsies obtained basally and after 1 year of treatment with fluvastatin). In the fluvastatin-treated group but not in the control group, we observed a significant reduction in cholesterol, low-density lipoprotein, and triglyceride. Clinical and laboratory assessment showed satisfactory tolerance of the drug by the patients. Proteinuria, serum albumin and creatinine clearance values were significantly better in the statin-treated patients. There was no difference in glomerular sclerosis between the 2 groups while interstitial fibrosis and renal fat deposits were less in the statin-treated group. The reduction in renal fat deposits in the statin-treated group was highly significant, while that of interstitial fibrosis was not. We conclude that: (1) statin can be safely and effectively used in the treatment of dyslipidemia in patients with persistent idiopathic nephrotic syndrome; (2) control of dyslipidemia in nephrotic patients is associated with better control of proteinuria and creatinine clearance; (3) statin treatment may cause regression of renal fat deposits in patients with nephrotic syndrome, and (4) longer term studies are still required to study further possible beneficial effects on renal histology and disease progression.

Topics: Adipose Tissue; Anticholesteremic Agents; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hyperlipidemias; Indoles; Kidney; Nephrotic Syndrome; Prospective Studies

The purpose of this study was to investigate the effect of fluvastatin on the microcirculation of patients with hyperlipidaemia (low-density lipoprotein cholesterol > 160 mg/dL, triglycerides < 350 mg/dl) inadequately controlled by diet. After a dietary run-in of 4 weeks, patients were randomised in a double-blind study to receive fluvastatin 40 mg twice daily (n = 24) or placebo (n = 24) for 12 weeks. The effect on microcirculation was assessed using capillary microscopy and laser Doppler fluxmetry at the nailfold at baseline and at 6 and 12 weeks after initiation of therapy. Capillaroscopy showed that fluvastatin improved microcirculation, i.e. time to peak flow during postocclusive reactive hyperaemia dropped from 19.7 +/- 7.2 s at baseline to 12.3 +/- 9.5 s at week 6 (P < 0.01) and 10.6 +/- 6.5 s at week 12 (P < 0.0001). These results were confirmed using laser Doppler fluxmetry to study microcirculation in thermoregulatory capillaries at the same site. A significant decrease in total and LDL-cholesterol was achieved during fluvastatin therapy. In conclusion, fluvastatin therapy improves microcirculation in nutritive as well as thermoregulatory capillaries in hypercholesterolaemic patients within 6 weeks.

Topics: Anticholesteremic Agents; Arteriosclerosis; Blood Proteins; Capillaries; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Fatty Acids, Monounsaturated; Fluvastatin; Hemostasis; Homocysteine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperemia; Hyperlipidemias; Indoles; Laser-Doppler Flowmetry; Microcirculation; Microscopy, Video; Risk Factors; Time Factors; Triglycerides

Although HMG-CoA reductase inhibitors (HMGRIs) are effective lipid-lowering agents, it remains controversial whether these agents also lower dense LDL (dLDL), a predominance of which is considered to contribute to the atherogenicity of the metabolic syndrome.. In a multicenter, double-blind, randomized, placebo-controlled study, we determined the effect of the HMGRI fluvastatin on lipids, apolipoproteins, and LDL subfractions (by equilibrium density gradient ultracentrifugation). A total of 52 postmenopausal women with combined hyperlipidemia and increased dLDL were treated with either fluvastatin 40 mg/d (n=35) or placebo (n=17). After 12 weeks' treatment, significant reductions (P<0.001) in total cholesterol (-19%), IDL cholesterol (-35%), LDL cholesterol (-23%), apolipoprotein B (-21%), and apolipoprotein B in dLDL (-42%) were apparent among fluvastatin recipients. No significant changes in triglycerides or HDL cholesterol were observed. The effect of fluvastatin on dLDL was correlated with baseline values. There was no consistent relationship, however, between the effect of fluvastatin on triglycerides and the decrease in dLDL.. Fluvastatin lowers total and LDL cholesterol and the concentration of dLDL. This profile may contribute to an antiatherogenic effect for fluvastatin that is greater than expected on the basis of changes in lipids and apolipoproteins.

Topics: Anticholesteremic Agents; Apolipoproteins B; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipoproteins; Lipoproteins, LDL; Phenotype; Postmenopause; Treatment Outcome; Triglycerides

During the last decades, transplantation has become an established tool for the treatment of terminal organ failure. Beside immunological factors, hyperlipidemia is the main problem after heart transplantation, causing rapid transplant coronary artery disease (TxCAD) and poor long-term prognosis at the beginning of the transplantation. Heart transplant recipients are now effectively treated with lipid lowering substances, of which HMG-CoA-reductase inhibitors are the most potent. However, treatment with these substances correlates with an increased risk for the development of rhabdomyolysis due to therapy with the immunosuppressive cyclosporine A. Our study monitored the safety and efficacy of treatment with the HMG-CoA reductase inhibitor fluvastatin in heart transplant recipients compared to healthy controls. We investigated 10 patients receiving immunosuppressive therapy consisting of cyclosporine A, prednisone, and azathioprine who had increased concentrations of LDL-cholesterol (LDL-C), and 10 age-matched healthy controls. The patients were treated with 40 mg/day fluvastatin for 4 weeks and 20 mg/day for 4 additional weeks. Control individuals received 40 mg/day fluvastatin for 4 weeks only. Parameters of fluvastatin pharmacokinetics (maximum concentration of the drug (C(max.)), time (t(max.)) to reach C(max.), area under the concentration vs. time curve (AUC(0h-24h)), elimination half-life time (t(1/2))), apparent total body clearance (CL), blood cyclosporine A concentration, plasma lipids, and safety parameters were determined in both study groups at the beginning of the study and after 4 weeks. The latter were determined in the patient group also after 8 and 12 weeks. Treatment with 40 mg/day fluvastatin caused a significant decrease in total cholesterol (patients: 5.47 +/- 1.32 mmol/L vs. 7.30 +/- 1.83 mmol/L; controls: 4.69 +/- 0.64 mmol/L vs. 5.81 +/- 0.72 mmol/L), LDL-C (patients: 3.28 +/- 1.25 mmol/L vs. 5.00 +/- 1.85 mmol/L; controls: 2.58 +/- 0.63 mmol/L vs. 3.50 +/- 0.70 mmol/L), and triglycerides (patients: 1.99 +/- 0.77 mmol/L vs. 2.50 +/- 1.00 mmol/L; controls: 1.24 +/- 0.46 mmol/L vs. 1.72 +/- 0.67 mmol/L) in both study groups, whereas HDL-C was not significantly changed (patients: 1.29 +/- 0.35 mmol/L vs. 1.17 +/- 0.32 mmol/L; controls: 1.55 +/- 0.30 mmol/L vs. 1.53 +/- 0.26 mmol/L). Values of C(max.) and AUC(0h-24h) were higher in the patient group than in the control group (day 1, patients vs. controls, C(max.): 869.4 +/- 604.0 ng/m

Topics: Adult; Aged; Anticholesteremic Agents; Area Under Curve; Cyclosporine; Drug Interactions; Drug Monitoring; Fatty Acids, Monounsaturated; Fluvastatin; Heart Transplantation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Immunosuppressive Agents; Indoles; Kidney Transplantation; Male; Middle Aged; Risk Factors; Time Factors

Posttransplant hyperlipidemia is a common complication which may affect long term cardiovascular mortality. In this prospective, placebo-controlled study, 19 renal transplant recipients (11 male 8 female, mean age 31.2 +/- 8.4 years) with good allograft function (serum creatinine <2 mg/dl) more than 6 months after transplantation were included. All the patients had hyperlipidemia (serum cholesterol >230 mg/dl and/or LDL-cholesterol >130 mg/dl) despite dietary interventions. The patients were treated with a triple immunosuppressive regimen. After a 8-week period of placebo plus diet regimen, the patients were put on fluvastatin plus diet for another 8 weeks. The patients were followed for its effect on lipid parameters and side effects. After convertion to fluvastatin, serum cholesterol (263.0 +/- 31.6 vs 223.2 +/- 31.6 mg/dl, p = 0.001), LDL-cholesterol (174.4 +/- 28.3 vs 136.4 +/- 28.5 mg/dl, p = 0.002), Apolipoprotein (Apo) A1 (131.1 +/- 16.9 vs 114.7 +/- 18.4 mg/dl, p = 0.001) and Apo B (109.0 +/- 29.8 vs 97.3 +/- 31.5 mg/dl, p = 0.02) levels decreased significantly. Serum levels of triglycerides, VLDL-cholesterol and HDL-cholesterol levels did not vary under fluvastatin. Serum lipoprotein (a) levels were also unchanged during the whole study period (24.9 +/- 19.4 vs 23.1 +/- 19.8 mg/dl, p > 0.05). We concluded that fluvastatin effectively decreased atherogenic lipoproteins such as serum cholesterol, LDL-cholesterol, Apo B in posttransplant hyperlipidemia, however fluvastatin had no effect on another independent risk factor of atherogenesis, serum lipoprotein (a) levels.

Topics: Adolescent; Adult; Anticholesteremic Agents; Apolipoproteins; Cholesterol; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Transplantation; Lipids; Lipoprotein(a); Lipoproteins, LDL; Male; Middle Aged; Prospective Studies; Treatment Outcome

Hyperlipidemia is an important cardiovascular risk factor. Lipid-lowering therapy has been shown to decrease morbidity and mortality in these patients. Combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and a fibric-acid derivative has been reported to be more efficacious to reduce low-density lipoprotein (LDL) cholesterol and triglycerides but may be associated with an increased risk of myositis. The aim of this study was to investigate the efficacy and tolerability of fluvastatin, an HMG-CoA reductase inhibitor, alone and in combination with bezafibrate, a fibric-acid derivative. In a randomized controlled trial with 454 hypercholesterolemic patients (mean cholesterol, 8.6 +/- 1.6 mM), fluvastatin (20 mg/day) significantly lowered total plasma cholesterol levels (-12.5%; p < 0.0001 vs. placebo), LDL cholesterol (-14%; p < 0.0001), and triglycerides (-4%; p = 0.05). A small increase in high-density lipoprotein (HDL) cholesterol levels (3%, NS) also was observed. Combination therapy with fluvastatin and bezafibrate (400 mg/day) in 71 patients with persistent hypertriglyceridemia during treatment with the statin resulted in a more pronounced reduction in triglyceride (-47%; p < 0.0001) and total cholesterol levels (-15%; p < 0.0001) than did fluvastatin alone. Furthermore, the additional bezafibrate significantly increased HDL cholesterol (+5%; p < 0.001). No significant increases in creatine phosphokinase levels or in frequency of myalgia were observed. In summary, fluvastatin decreases both cholesterol and triglyceride levels. In patients with persistent hypertriglyceridemia, combination therapy with fluvastatin and bezafibrate may be safely used to lower triglyceride and cholesterol levels more efficiently.

Topics: Adult; Aged; Bezafibrate; Cholesterol; Double-Blind Method; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypertriglyceridemia; Hypolipidemic Agents; Indoles; Male; Middle Aged

Topics: Angioplasty, Balloon, Coronary; Anticholesteremic Agents; Atorvastatin; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Indoles; Pyrroles

To establish whether patients receiving the cholesterol synthesis enzyme inhibitor fluvastatin 20 mg/day could obtain an additional improvement in their lipid pattern as a result of physical endurance training.. This was an observational study using a before- and after-treatment comparison of fitness and lipid parameters in outpatients with dyslipidaemia who undertook an exercise programme with or without treatment with a lipid-lowering drug.. Participants were 18 sedentary [maximum oxygen uptake (VO2max) < 30 ml/kg bodyweight per minute] men (age range 38 to 65 years) with dyslipidaemia but without overt cardiovascular disease.. All participants undertook a 1-hour bout of endurance training twice a week for 3 months. The training involved a circuit using various ergometers, with continuous monitoring of pulse rate, at an exercise intensity of 2 to 3 mmol/L lactate. The control group (n = 6) received no drug treatment; they completed the training programme only. The pretreatment group (n = 6) comprised participants who had already been treated with fluvastatin 20 mg/day for at least 3 months before beginning the training programme. The treatment group (n = 6) received fluvastatin 20 mg/day from the beginning of the training programme. All participants were required to comply with the exercise programme and with a standardised carbohydrate-loaded diet together with restriction of alcohol consumption to a maximum of 20 ml/day.. In the control group, increased physical activity alone reduced serum triglyceride (TG) levels (-24.7%) and increased serum high density lipoprotein-cholesterol (HDL-C) levels (+19.3%). There was a smaller effect on serum low density lipoprotein-cholesterol (LDL-C) levels (-12.8%). Similar but smaller effects were observed in the pretreatment group (i.e. patients previously treated with fluvastatin): TG -12.88%, HDL-C +13.81%, LDL-C -8.7%. Marked changes were observed in the treatment group: TG -33.1%, HDL-C +34.7%, LDL-C -40.5%, total cholesterol -30.5%.. A reduction of serum LDL-C level in the target range of -30 to -40% cannot be achieved by this intensity of training alone. In combination with fluvastatin 20 mg/day, however, the positive effects on lipid metabolism are potentiated. Thus, treatment with fluvastatin combined with moderate endurance training is a rational mode of therapy, particularly in patients with a highly pathological lipid profile.

Topics: Adult; Aged; Combined Modality Therapy; Exercise Therapy; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Physical Endurance; Reference Values; Treatment Outcome

The primary objective of the present study was to investigate the cholesterol-lowering effect of fluvastatin on the incidence of cardiac events in hyperlipidaemic patients with symptomatic, clinically-diagnosed (exercise-ECG) coronary heart disease (CHD) during 1 year of treatment. Exercise tolerance, incidence of angina pectoris episodes, use of anti-anginal medication and intimal-medial-thickness (IMT subgroup) of the A. carotis were secondary endpoints. In the double-blind trial a total of 365 male and female patients with stable symptomatic CHD and a low-density lipoprotein cholesterol (LDL-C) above 160 mg/dl on a lipid-lowering diet were randomised to fluvastatin 40 mg (o.a.d. or b.i.d.) or placebo for 1 year. Fluvastatin lowered total cholesterol by 17% and LDL-C by 27%. There was a significantly lower incidence of cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina pectoris) in the fluvastatin group (3 events) as compared to the placebo group (10 events) (P < 0.05). Exercise tolerance improved and the incidence of angina pectoris episodes decreased in both groups, but more pronounced on fluvastatin (n.s.). Exercise-ECG discontinuation due to angina pectoris and ST-segment depression decreased in the fluvastatin group by 55.6 and 70.9%, respectively, and in the placebo group by 39.6 and 46.5% (n.s.). At baseline, a subgroup of 76 patients showed a mean IMT value of 0.73 mm which remained uninfluenced in the fluvastatin and the placebo groups. Fluvastatin was safe and well tolerated. In conclusion, patients with symptomatic CHD get cardiovascular benefit from lipid-lowering therapy with fluvastatin even during the first year of treatment.

Topics: Adult; Aged; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Coronary Vessels; Double-Blind Method; Exercise Tolerance; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Middle Aged; Treatment Outcome; Tunica Intima; Ultrasonography

The influence of fluvastatin, a liver-selective, competitive inhibitor of the 3-hydroxymethyl-glutaryl-coenzyme A reductase, on the lipoprotein metabolism was investigated in 9 patients with nephrotic syndrome. All patients had biopsy-proven renal disease as cause of their nephrotic syndrome and exhibited severe hyperlipidemia [baseline: serum cholesterol 358 +/- 46 mg/dl (9.3 mmol/l), low-density lipoprotein cholesterol 236 +/- 18 mg/dl (6.1 mmol/l), triglycerides 333 +/- 28 mg/dl (3.8 mmol/l), and lipoprotein Lp(a) 46 +/- 11 mg/dl]. After 1 year of 40 mg of fluvastatin, significant reductions of total cholesterol by 31% to 242 +/- 26 mg/dl (6.3 mmol/l) and low-density lipoprotein cholesterol by 29% to 162 +/- 12 mg/dl (4.2 mmol/l) were observed. Furthermore, triglyceride values were also lowered significantly by 19% to 268 +/- 21 mg/dl (3.1 mmol/l). Lipoprotein Lp(a) and high-density lipoprotein-cholesterol remained unchanged by fluvastatin. These improvements in lipid profile were maintained during the entire follow-up period of 1 year. There were no adverse events, and the slight increase in serum creatinine observed during the study was considered to be due to the primary renal disease. In conclusion, long- term administration of fluvastatin in patients with nephrotic syndrome appears to be an effective and safe treatment of the hyperlipidemia associated with this disorder.

Topics: Adult; Cholesterol; Fatty Acids, Monounsaturated; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Indoles; Nephrotic Syndrome; Prospective Studies; Time Factors

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

Although myopathy is considered an adverse effect of treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors and fibrates in combined hyperlipidemia, the present study was performed to investigate whether combined hyperlipidemia itself is associated with skeletal muscle pathology and whether lipid-lowering intervention has beneficial effects. To investigate whether combined hyperlipidemia is associated with skeletal muscle pathology, 10 male patients and 15 normolipidemic controls underwent a 45-minute standardized bicycle ergometer test at a load of 2 W/kg lean body mass (parallel study). One- and 8-hour postexercise increments in the plasma level of the muscle proteins creatine kinase (CK), myoglobin (Mb), and fatty acid-binding protein (FABP) were assessed as parameters for (subclinical) skeletal muscle pathology. The 8-hour postexercise increments in CK and Mb and 1-hour postexercise increment in Mb were significantly higher in patients than in controls, thus indicating increased exercise-induced muscle membrane permeability in combined hyperlipidemia. To investigate the effects of lipid-lowering intervention on skeletal muscle in combined hyperlipidemia, 21 subjects with combined hyperlipidemia were randomized double-blindly to receive 6 weeks of treatment with fluvastatin 40 mg/d, gemfibrozil 600 mg twice daily, or combination therapy. All subjects underwent an ergometer test before and after treatment. Gemfibrozil treatment alone reduced the CK increments 8 hours postexercise by 47% and the FABP increments 1 and 8 hours postexercise by 83% and 101%, respectively (all P < .05). Combined treatment reduced Mb increments 1 hour postexercise by 54% and FABP increments 8 hours postexercise by 44% (all P < .05). A highly significant correlation existed between therapy-induced changes in plasma triglycerides and changes in postexercise increments of FABP and Mb. In conclusion, combined hyperlipidemia is associated with an increased exercise-induced release of muscle proteins, which is ameliorated by triglyceride-lowering intervention. As FABP is an indicator for ischemia-induced skeletal muscle pathology, a possible explanation is the impaired muscle blood flow during hypertriglyceridemia, which may be reversed by triglyceride-lowering intervention. The mechanism and clinical relevance of these findings remain to be investigated.

Topics: Double-Blind Method; Drug Therapy, Combination; Exercise; Exercise Test; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gemfibrozil; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Infant, Newborn; Lipids; Male; Middle Aged; Muscle Proteins; Reference Values; Triglycerides

The long-term efficacy and safety of fluvastatin monotherapy was compared with that of the combination of fluvastatin and fenofibrate in 104 patients with coronary heart disease and combined hyperlipidemia in an open, randomised, parallel group, clinical study of 78 weeks duration. Combined hyperlipidemia was defined as LDL-cholesterol 4.1 mmol/l and higher and triglycerides between 2.5 and 4.5 mmol/l after 8 weeks of dietary intervention. The patients were treated with either fluvastatin 40 mg daily or with the combination of fluvastatin (20 mg daily) and micronized fenofibrate 200 mg daily. Mean values of total and LDL-cholesterol decreased by 19.3% and 29.7% respectively after fluvastatin treatment and by 21.5% and 29.1% respectively after the combination of fluvastatin and fenofibrate treatment. The differences between the treated groups were not significant. Mean values of HDL-cholesterol increased significantly more after the combination of fluvastatin and fenofibrate than after fluvastatin monotherapy (26% vs. 9.9%). The mean values of triglycerides decreased significantly more after the combination treatment than after fluvastatin monotherapy (-40.2% vs. -19.7%). The treatment in both groups was well tolerated and no signs of myopathy were observed in any patient. The study was discontinued in 1 patient due to the increase of liver enzymes. The most frequently observed side effects were minor gastrointestinal symptoms, which were more frequent in patients treated by the combination of fluvastatin and fenofibrate. Thus our results demonstrate that the combination of fluvastatin and fenofibrate is an effective and safe treatment option for patients with coronary heart disease and mild to moderate combined hyperlipidemia if a more radical lowering of triglycerides and increase of HDL-cholesterol is desired.

Topics: Adult; Aged; Coronary Disease; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Indoles; Male; Middle Aged

To analyse the efficacy of health education (HE) through group session with postal back-up in furthering compliance with therapy for Lipaemia.. Controlled clinical trial, with random distribution.. Primary care.. 110 patients with Hypercholesterolaemia, with new diagnoses or not in treatment, in which medical treatment with statins was indicated as a start or change in medication.. They were distributed in two groups at random, with observation four months after being included in the study and appointments after one, two and four months. 1. Control group (CG): 55 patients who received HE from their family doctor. 2. Intervention group (IG): 55 patients whose HE was monitored: a) a group HE session and b) back-up by letter sent to their homes.. Patients whose consumption was between 80 and 110% of the amount prescribed were defined as compliant. The pill count was recorded. The percentages of compliant patients and mean compliance (chi squared, Student's t) were analysed. 108 individuals, 41 men and 67 women, completed the trial. There was no difference between the two groups as to age, sex, evolution time, number of diseases and dosage of medicines consumed. 71.3% were compliant (CI, 62.8-79.8%), CG = 61.8% and IG 81.1% (p < 0.05). The mean percentage of compliance was 86.1 +/- 14.3 overall, with CG = 83.8 +/- 14 and IG 88.5 +/- 14 (p = NS).. The HE intervention with a group session and postal back-up is an effective way of improving therapeutic compliance in cases of hypercholesterolaemia.

Topics: Adolescent; Adult; Aged; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Male; Middle Aged; Patient Compliance; Patient Education as Topic; Tablets; Time Factors

Topics: Adult; Aged; Anticholesteremic Agents; Cyclosporine; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gingival Hyperplasia; Hirsutism; Humans; Hyperlipidemias; Immunosuppressive Agents; Indoles; Kidney Transplantation; Lovastatin; Male; Middle Aged; Pravastatin; Tacrolimus

62 patients with hyperlipidemia II and hypertension were 8 weeks on low fat and low cholesterol diet (acc. to EAS recommendations). If LDL-Ch > or = 4.1 mmol/l the diet was continued and 12 weeks treatment by fluvastatin (Lescol, Sandoz Pharma Ltd) started with control every 4 weeks Preliminary dosage 20 mg once daily in the evening increased to 40 mg if LDL-Ch > 3.5 mmol/l. After 12 weeks the mean level of T.Chol decreased by 21%, LDL-Ch by 29%, LDL-Ch/HDL-Ch by 31% and T.Chol/HDL-Ch by 24%. HDL-Ch increased by 8% and TG decreased by 5% but not significantly. The first goal of treatment (LDL-Ch < 4.14 mmol/l) achieved 73% and second (LDL-Ch < or = 3.5 mmol/l)-43.3% patients. In 2 patients treatment was discontinued (in one due to severe alimentary symptoms and in second-due to infection of respiratory tract with increase of SGOT and SGPT) and in next 2 the dosage was decreased to 20 mg/day (due to transitory alimentary symptoms).

Topics: Anticholesteremic Agents; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diet, Fat-Restricted; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Hypertension; Indoles; Male; Middle Aged; Triglycerides

A single, blinded placebo-drug trial was conducted to study the efficacy and safety of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in treating dyslipoproteinemia in 16 renal transplant recipients who had been on an immunosuppressive regimen that included cyclosporine (CsA). They were studied for 32 consecutive weeks, with 4 weeks of baseline treatment, 4 weeks of placebo, 12 weeks of treatment with fluvastatin 20 mg daily, and 12 weeks of fluvastatin 40 mg daily. Blood samples were obtained every 4 weeks for measurement of the lipoprotein profiles, which included total cholesterol (TC), triglyceride, low density lipoprotein (LDL)-, high density lipoprotein (HDL)-, HDL2-, HDL3- and very low density lipoprotein-cholesterol (C), apolipoprotein (Apo) A-1, Apo B, and lipoprotein(a). Fifteen patients completed the trial. After 12 weeks of treatment, fluvastatin 20 mg significantly reduced TC by 13.4% (from 6.7 +/- 0.5 [mean +/- SEM] to 5.8 +/- 0.2 mmol/L), LDL-C by 22% (from 4.1 +/- 0.3 to 3.2 +/- 0.2 mmol/L), and Apo B by 13.2% (from 159.6 +/- 8.8 to 138.6 +/- 9.2 mg/dl) (P < 0.005). The subsequent 12-week treatment of fluvastatin 40 mg significantly reduced TC by 16.4% to 5.6 +/- 0.3 mmol/L, LDL-C by 29.3% to 2.9 +/- 0.2 mmol/L, and Apo B by 18.2% to 130.6 +/- 5.5 mg/dl (P < 0.00005). There was no significant change in levels of other lipoproteins, including lipoprotein (a). There were no significant changes in the whole blood trough CsA concentrations, renal and liver function tests, and serum creatine phosphokinase level during treatment when compared with baseline and placebo. No patient complained of myalgia or failed to complete the study due to side effects of the drug. Fluvastatin appears to be safe and effective in treating dyslipoproteinemia in renal transplant recipients who are maintained on CsA.

Topics: Adult; Anticholesteremic Agents; Cyclosporine; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Immunosuppressive Agents; Indoles; Kidney Transplantation; Lipoproteins; Male; Placebos; Potassium; Prospective Studies; Single-Blind Method

Although combination therapy using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co-A) reductase inhibitors and fibrates is efficacious in combined hyperlipidemia, such treatment has been associated with myopathy. For this reason, we studied the effects of fluvastatin and gemfibrozil, alone or in combination, on muscle. A total of 21 patients with combined hyperlipidemia were recruited who were matched for age, body mass index, and baseline levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides, creatine phosphokinase, and myoglobin. Patients were randomized to three groups for 6-week treatment with fluvastatin at 40 mg/day, gemfibrozil at 600 mg twice daily, or a combination of the two drugs. Parameters for muscle damage were rises in levels of serum creatine phosphokinase and myoglobin compared with pre-exercise levels; these were assessed 1 hr and 8 hr after a 45 min lean body mass standardized ergometer test, which was performed before and after treatment in all patients. Biopsies from the quadriceps muscle were taken 48 hr after each test. Fluvastatin lowered total cholesterol and LDL-C by 23% and 35%, respectively (p < 0.01), with no effects on triglycerides and HDL-C. Gemfibrozil lowered triglycerides by 40% (p < 0.01) but did not lower total cholesterol or LDL-C significantly. The combination therapy decreased total cholesterol, LDL-C, and triglycerides by 28%, 29%, and 39%, respectively (p < 0.05). Pre-exercise creatine phosphokinase and myoglobin levels were not affected by treatment in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticholesteremic Agents; Biopsy; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Creatine Kinase; Double-Blind Method; Drug Combinations; Exercise Test; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gemfibrozil; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Middle Aged; Muscle, Skeletal; Myoglobin; Placebos; Prospective Studies; Triglycerides

High-risk patients with dyslipidemias resistant to diet and single-agent pharmacotherapy may require combination therapy to achieve target levels of low density lipoprotein, triglycerides, and high density lipoprotein. Combinations of fibrates and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors are effective, but because of safety concerns related to myopathy and rhabdomyolysis, it is important to consider the possibility of pharmacokinetic interactions when such combinations are used. In this study, the area under the curve, maximum plasma concentration, and time to maximum concentration for fluvastatin and gemfibrozil are compared, when used alone and in combination, in patients with hyperlipidemia and either coronary or carotid atherosclerosis, or a family history of coronary artery disease. A total of 17 patients were studied in a random sequence, open-label, crossover study of fluvastatin at 20 mg twice daily, gemfibrozil at 600 mg twice daily, and the combination of the 2 drugs. No significant difference was observed in area under the curve, maximum plasma concentration, and time to maximum concentration when comparing the combination with each drug alone. These pharmacokinetic data add support to the clinical observations that the combination of fluvastatin and gemfibrozil is both effective and safe.

Topics: Anticholesteremic Agents; Arteriosclerosis; Carotid Stenosis; Coronary Artery Disease; Coronary Disease; Cross-Over Studies; Drug Combinations; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gemfibrozil; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Pilot Projects; Placebos; Safety; Triglycerides

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

Limited data are available on the relapse of statin intolerance after resumption of statins. We aimed to evaluate the relapse rates of statin intolerance in patients who subsequently received pravastatin or fluvastatin and to identify associated factors.. This retrospective, propensity score-matched cohort study screened data obtained from a tertiary university hospital between 2006 and 2015. Of 8073 patients screened, 488 with statin intolerance who received pravastatin or fluvastatin with regular follow-up were enrolled. After propensity score matching of patients, 384 were finally analyzed. The primary outcome variables were relapse of statin intolerance and stopping (ie, discontinuation or switching to other statins) rate for the 2 statins.. During the median follow-up period of 37 months, the rate of relapse of intolerance was 10.4% and 18.2% among users of pravastatin and fluvastatin, respectively (P = 0.04). However, the log-rank test showed no difference in the relapse-free rates between the 2 groups (P = 0.34). The stopping rates of the 2 statins were 36.5% and 42.2% (P = 0.30), respectively, for various reasons, including low efficacy of the drugs. After adjustment, chronic kidney disease (hazard ratio [HR] 1.83, P = 0.03) and previous creatine kinase elevation (HR 3.13, P = 0.001) were identified as independent determinants of relapse. Older age (HR 1.03, P = 0.057) and female sex (HR 1.70, P = 0.059) were associated, but not significantly, with relapse.. Although a small proportion of patients taking pravastatin or fluvastatin experienced a relapse of intolerance, many patients eventually discontinued or changed these agents. Chronic kidney disease and history of creatine kinase elevation were independent determinants of relapse.

Topics: Aged; Biomarkers; Creatine Kinase; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Kidney Failure, Chronic; Male; Middle Aged; Pravastatin; Propensity Score; Retrospective Studies; Risk Factors

Atherosclerosis is the major cause of cardiovascular disease; hypercholesterolemia is a major risk factor. We hypothesized that specific TLR members (TLR2, TLR3, TLR4, TLR8) may play a role in atherosclerosis progression and its accompanying inflammatory response. We determined the association of atherosclerotic lesions and TLR mRNA expression in different aortic sites. We also assessed the effects of fluvastatin (Flu) treatment on TLR expression and plaque characteristics.. Male rabbits, fed with an atherogenic diet for a duration of 3 months, were screened for advanced atherosclerotic lesions in the aorta. Additional animals received normal diet or normal diet plus Flu for 1 additional month. TLR mRNA expression in various thoracic and abdominal aortic segments was assessed, together with atherosclerotic changes.. After high lipid diet, the atherosclerotic burden increased more in the abdominal than in the thoracic aorta; TLR2, 3, 4, and 8 also increased significantly. Flu decreased atherosclerotic plaque, calcium deposition, lipid cores, intraplaque hemorrhage, erythrocyte membranes, endothelial cells, and macrophage infiltration, while increasing smooth muscle cells in plaques of both aortic segments; it also lowered TLR2, 3, 4, and 8 expression in all aortic segments to a stronger degree than resumption of normal diet. There was a strong association between blood and tissue parameters during experimental period and finally a strong correlation found between these parameters with mRNA of TLR2, 3, 4, and 8 in various stages.. For the first time TLR2, 3, 4, and 8 mRNA expression is prospectively explored after hypercholesterolemic diet in the rabbit model. TLR2, 3, 4, and 8 mRNA expression is strongly upregulated and correlates with the progression of atherosclerosis in the aorta. Flu significantly inhibited this progress and reduced inflammation via TLR downregulation which was strongly associated with regression of plaque morphology and atherosclerosis promoting factors.

Topics: Animals; Aorta, Abdominal; Aorta, Thoracic; Aortic Diseases; Atherosclerosis; Diet, Atherogenic; Disease Models, Animal; Disease Progression; Fatty Acids, Monounsaturated; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Plaque, Atherosclerotic; Rabbits; Toll-Like Receptor 2; Toll-Like Receptor 3; Toll-Like Receptor 4; Toll-Like Receptor 8; Up-Regulation

Antilipidemics are widely applied to reduce the risk of cardio- and cerebrovascular events. The purpose of this case report is to illustrate the clinical and radiological findings of focal myositis as a side effect of statins and fibrates in 2 patients with forearm involvement. These 2 cases demonstrate that a targeted medical history taking and use of MRI to support the suspected diagnosis, can efficiently facilitate the route to an appropriate therapy.

Topics: Anticholesteremic Agents; Atorvastatin; Bezafibrate; Coronary Disease; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Forearm; Heptanoic Acids; Humans; Hyperlipidemias; Image Interpretation, Computer-Assisted; Indoles; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Myositis; Pyrroles

Currently used hypolipidemic drugs, Fluvastatin and Atorvastatin, act via inhibiting the rate-limiting enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase of the mevalonate pathway. The associated severe side-effects of these statins led us to explore the therapeutic potentials of naturally occurring Tocomin (mixture of dietary α-, β-, γ- and δ-tocotrienols). Tocomin (10 mg) was orally administered daily for 10 days before and 12 h after bacterial lipopolysaccharide (200 μg) or 24 h after zymosan (20 mg) or turpentine (0.5 mL) to Syrian hamsters. The data showed that Tocomin significantly reduced the levels of plasma and lipoprotein lipids, cholesterol, apoB, small dense (sd)-LDL as well as LDL in the hyperlipidemia-induced hamsters. Further, the mechanism of action of α-, β-, γ- and δ-tocotrienols was validated by docking studies with HMG-CoA reductase enzyme using the Molegro Virtual Docker. The inhibition of HMG-CoA reductase predicted in terms of MolDockScore and interaction energy suggest the comparative potential in the descending order: Atorvastatin > Fluvastatin ~ δ > γ > β > α. The results favor the daily intake of naturally occurring tocotrienols as dietary supplement in the prevention and treatment of infection/inflammation induced dyslipidemia compared with the hypolipidemic drugs.

Topics: Administration, Oral; Animals; Atorvastatin; Cholesterol; Cricetinae; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipid Metabolism; Lipoproteins, LDL; Male; Molecular Structure; Pyrroles; Tocotrienols

Topics: Animals; Cricetinae; Fatty Acids, Monounsaturated; Fluvastatin; Gene Expression Regulation; HMGB1 Protein; Hyperlipidemias; Indoles; Male; Mesocricetus; Random Allocation

Topics: Animals; Anticholesteremic Agents; Evidence-Based Medicine; Fatty Acids, Monounsaturated; Fluvastatin; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Prospective Studies; Treatment Outcome

Statins (HMG-CoA reductase inhibitors) are one of the most widely prescribed classes of drugs throughout the world, because of their excellent cholesterol-lowering effect and overall safety profile except for rare but fatal rhabdomyolysis arising either directly or indirectly by pharmacokinetic interactions with certain other drugs. As package inserts in pharmaceuticals are the primary source of information for health care providers, we carried out a literature search to examine how crucial information was provided in package inserts of five statins approved in Japan (simvastatin, atorvastatin, fluvastatin, pravastatin and pitavastatin).. A MEDLINE search from 1996 to June 2004 was carried out to identify studies on clinical pharmacokinetic drug interactions for the five statins. We mainly collected information on area under plasma concentration (AUC) following co-administration of statins with other drugs. The current package inserts used in Japan were obtained from the website of the Pharmaceutical and Medical Device Agency whereas USA package inserts were obtained from the Food and Drug Administration website.. The majority of package inserts listed the drugs that interacted with statins with most describing the risk of rhabdomyolysis because of the possibility of increases in blood concentration. However, quantitative information such as change in AUC was provided in only a few cases. Instructions for dosage adjustment are seldom provided in the Japanese package inserts. USA package inserts list almost identical drug interactions as the Japanese package inserts, although they contain more quantitative data, especially for typical cytochrome P450 (CYP) inhibitors.. All pharmacokinetic drug interactions including relevant quantitative data for potential effectors and details on mechanisms of interaction need to be given in package inserts as soon as the information becomes available, to ensure safe and proper use of the drugs concerned. Including such information in the package insert will be an extremely valuable aid for health care providers.

Topics: Area Under Curve; Atorvastatin; Biomedical Research; Databases, Bibliographic; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Japan; Pharmacology, Clinical; Pravastatin; Product Labeling; Pyrroles; Quinolines; Simvastatin; United States; United States Food and Drug Administration

Drug-drug interactions (DDIs) are a well known risk factor for adverse drug reactions. HMG-CoA reductase inhibitors ('statins') are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia.. Data from patients with dyslipidaemia treated with a statin were collected from 242 practitioners from different parts of Switzerland. The medication list was screened for potentially harmful DDIs with statins or other drugs using an interactive electronic drug interaction program.. We included 2742 ambulatory statin-treated patients (mean age +/- SD 65.1 +/- 11.1 years; 61.6% males) with (mean +/- SD) 3.2 +/- 1.6 diagnoses and 4.9 +/- 2.4 drugs prescribed. Of those, 190 patients (6.9%) had a total of 198 potentially harmful drug-statin interactions. Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug-statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a potential drug-statin interaction was 12.1% for simvastatin, 10.0% for atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the program identified 393 potentially critical non-statin DDIs in 288 patients.. CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins. As the risk for developing rhabdomyolysis is increased in patients with drug-statin interactions, clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.

Topics: Aged; Ambulatory Care; Aryl Hydrocarbon Hydroxylases; Atorvastatin; Comorbidity; Cross-Sectional Studies; Cyclosporine; Cytochrome P-450 CYP3A; Digoxin; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Niacin; Oxidoreductases, N-Demethylating; Physicians; Pravastatin; Prevalence; Product Surveillance, Postmarketing; Pyrroles; Simvastatin; Time Factors

Hyperhomocysteinemia induces vascular endothelial dysfunction, contributing to a predisposition to the onset and/or progression of atherosclerosis. The major mechanism suggested for the adverse effect of homocysteine on vascular function seems to involve oxidative stress. Thus, we hypothesized that the administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin, which is experimentally demonstrated to have antioxidative properties as one of its pleiotropic effects, is a useful strategy for eliminating the detrimental events induced by hyperhomocysteinemia.. In diet-induced hyperhomocysteinemic rats, we estimated oxidative stress and assessed endothelium-dependent vasodilatation. Hyperhomocysteinemia induced significant increases in urinary 8-isoprostaglandin F2alpha-III excretion and vascular superoxide generation, and impaired endothelium-dependent vasodilatation. Additional oral administration of the antioxidant fluvastatin or vitamin E, which normalized increased oxidative stress induced by hyperhomocysteinemia, ameliorated endothelial dysfunction.. Hyperhomocysteinemia, even mild to moderate, induces endothelial dysfunction through its oxidative effect. The antioxidant fluvastatin was able to cancel out the oxidative stress induced by hyperhomocysteinemia and ameliorate endothelial dysfunction. Clinical use of fluvastatin might be a potent strategy for eliminating the detrimental events induced by hyperhomocysteinemia as well as hyperlipidemia. In addition to lowering homocysteine by means of folate supplementation, administration of the antioxidants is expected to be a potentially effective anti-homocysteine therapy.

Topics: Animals; Antioxidants; Disease Models, Animal; Endothelium, Vascular; Fatty Acids, Monounsaturated; Fluvastatin; Hyperhomocysteinemia; Hyperlipidemias; Indoles; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Vasodilation; Vitamin E

Topics: Cardiovascular Diseases; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fish Oils; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Risk Factors

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: Cardiovascular Diseases; Clinical Trials as Topic; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Diseases; Kidney Transplantation; Quality Control; Risk Factors

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Diseases; Kidney Transplantation; Quality Control; Risk Factors

Heart rate recovery is the difference in heart rate at peak exercise and at a specific time interval following the onset of recovery. Attenuated heart rate recovery is an independent predictor of mortality in patients with a history of coronary artery disease. The aim of the present study was to evaluate the effect of a statin on heart rate recovery, particularly in patients with ischemic heart failure and hyperlipidemia. Twenty-nine consecutive hyperlipidemic, stable coronary artery disease patients with heart failure and 19 healthy subjects were enrolled. Heart rate recovery values at the 1st and 3rd minutes and lipid profiles of the patients were evaluated at baseline and following 3 months of treatment with fluvastatin. Compared with healthy subjects, the heart rate recovery values were significantly lower in the heart failure patients in both the 1st and 3rd minutes, respectively (31 +/- 6 versus 19 +/- 7, P < 0.0001; 66 +/- 7 versus 47 +/- 8, P < 0.0001). Heart rate recovery in the 1st and 3rd minutes increased from 19 +/- 7 to 24 +/- 9 and 47 +/- 8 to 57 +/- 11, respectively, following treatment (P < 0.001, P < 0.001). There were no significant correlations among the changes in lipid parameters or HRR in the first and third minutes in the recovery period. The results revealed an improvement in heart rate recovery in heart failure patients by fluvastatin treatment. If this association can be confirmed by other studies, it would be interesting to perform further studies into the mechanism underlying this finding.

Topics: Aged; Anticholesteremic Agents; Coronary Artery Disease; Exercise; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heart Failure; Heart Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipids; Male; Middle Aged; Parasympathetic Nervous System; Recovery of Function

Our goal is to show the effectiveness of fluvastatin in reducing arterial sclerosis using integrated backscatter (IB) values rather than depending on the pulse-wave velocity (PWV) and stiffness beta.. Atherosclerotic changes consist of two components: atherosis as a structural change and sclerosis as a functional change; IB ultrasound of carotid media was useful for assessment of arterial sclerosis.. We measured IB values in the media of 40 segments of carotid arteries in 40 patients with hyperlipidemia before and after statin therapy or diet for 12 months (fluvastatin [F group] 40 mg/day, n = 20; control [C group]: diet, n = 20). Pulse-wave velocity, intima-media thickness, and stiffness beta were measured at the same time.. At baseline, IB values correlated with PWV (r = 0.71, p < 0.001) and stiffness beta (r = 0.47, p = 0.002) in 40 patients with hyperlipidemia. Integrated backscatter values did not change in the C group but decreased in the F group (from 12.3 +/- 2.1 dB to 11.3 +/- 2.1 dB, p = 0.002). Also, PWV increased in the C group (from 1,728 +/- 687 cm/s to 1,771 +/- 716 cm/s, p = 0.021) but decreased in the F group (from 1,848 +/- 582 cm/s to 1,768 +/- 549 cm/s, p = 0.012). Stiffness beta decreased in the F group (from 14.0 +/- 3.9 to 12.1 +/- 3.5, p = 0.002).. Statin therapy with fluvastatin improved arterial sclerosis as assessed by IB values.

Topics: Adult; Aged; Carotid Arteries; Carotid Artery Diseases; Elasticity; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipids; Male; Middle Aged; Tunica Media; Ultrasonography

Our primary objective was to obtain robust estimates of the low-density lipoprotein cholesterol (LDL-C) decrease from baseline over a long period (ie, 3 years) after initiation of statin treatment in a usual-care setting. Our secondary objective was to investigate the predictors of the LDL-C time course.. We retrospectively analyzed the data for a sample of enrollees in a health maintenance organization (HMO) who started statin treatment between October 1, 1995, and December 31, 1998. Using the HMO's claims database, we examined the LDL-C change from baseline (as measured at the prescribing physicians' discretion) and computed mean estimates every 6 months up to 3 years. We investigated potential predictors of the LDL-C time course (ie, age, sex, baseline LDL-C, previous treatment, prescribing physician's specialty, and most recent treatment) with a mixed model applied to longitudinal data. This model enabled us to impute missing data for all enrollees still being followed, including those who had stopped treatment, and to discuss the robustness of our findings. We applied 2 methods of imputation, assuming either of the following: (1) data were missing at random but could be estimated from the parameters in the mixed model, or (2) LDL-C returned to the baseline value > or =15 days after treatment cessation.. We examined data from 3193 individuals. In most cases, the statin used was fluvastatin or pravastatin. The observed mean (95% CI) LDL-C decrease from baseline widened progressively from 23.6% (23.0%-24.3%) at 6 months to 28.0% (27.1%-28.9%) at 18 months and 30.2% (28.7%-31.7%) at 36 months after treatment initiation. These results remained robust after the imputation of missing data, with mean LDL-C reduction consistently >20% at each 6-month time point during the 3 years after treatment initiation. Variations as a function of baseline characteristics were limited (demographics) or explicable by extraneous factors (baseline LDL-C). There were predictable variations as a function of the most recent treatment.. This analysis indicates a long-term reduction in LDL-C among a sample of HMO enrollees who initiated statin treatment in a usual-care setting. The results were robust after imputation of missing data, with mean decrease from baseline consistently >20% over 3 years. However, given the retrospective design of our study and the absence of a control group, we cannot determine how much of the decrease was attributable to treatment.

Topics: Aged; Anticholesteremic Agents; Cholesterol, LDL; Data Interpretation, Statistical; Fatty Acids, Monounsaturated; Female; Fluvastatin; Health Maintenance Organizations; Humans; Hyperlipidemias; Indoles; Long-Term Care; Male; Middle Aged; Pravastatin; Retrospective Studies; Time Factors

Cigarette smoking is known to promote atherosclerosis, possibly through enhanced oxidative stress. The aim of the present study was to elucidate the possible involvement of peroxynitrite in oxidative modification of low-density lipoprotein (LDL) induced by aqueous extract of cigarette smoke (CSE) and the preventive effect of fluvastain, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor with antioxidative activity, in vitro and in vivo. Modification of LDL was monitored by LDL subfraction analysis using anion-exchange HPLC, TBARS formation and 3-nitrotyrosine production. Incubation of LDL with CSE caused a marked increase in oxidative modification of LDL and nitration of tyrosine residues in the apolipoprotein B. These modifications were prevented by treatment with fluvastatin as well as Vitamin E in a concentration-related manner. Fluvastatin was equal to or more effective than Vitamin E for preventing protein nitration, but weaker for preventing oxidative modification. When CSE was injected daily into the ear vein of Watanabe heritable hyperlipidemic rabbits for 5 months, both oxidative modification and nitration of the plasma LDL noticeably occurred. These changes induced by CSE could be effectively prevented by the simultaneous oral administration of fluvastatin (10 and 30 mg/kg) or Vitamin E (150 mg/kg). Fluvastatin prevented the LDL nitration more effectively than Vitamin E. These results suggest that peroxynitrite in CSE is involved in oxidative modification of LDL and that fluvastatin can efficiently prevent LDL modification by scavenging peroxynitrite. Fluvastatin may be potentially beneficial to hypercholesterolemic patients with oxidative stress such as smoking.

Topics: Animals; Antioxidants; Apolipoproteins; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; In Vitro Techniques; Indoles; Lipoproteins, LDL; Male; Oxidation-Reduction; Oxidative Stress; Peroxynitrous Acid; Rabbits; Smoking; Tyrosine; Vitamin E

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

Topics: Adult; Bezafibrate; Creatine Kinase; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fluvastatin; Gemfibrozil; Humans; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Indoles; Male; Middle Aged

Topics: Adult; Anticholesteremic Agents; Atorvastatin; Dinoprost; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Isoprostanes; Lovastatin; Male; Middle Aged; Pravastatin; Pyrroles; Simvastatin; Smoking

Recent evidence suggests that the beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on entothelial function and cardiovascular ischemic events may be attributed not only to their lipid-lowering effects but also to cholesterol-lowering independent (direct) effects on the atherosclerotic vessel wall. This study was designed to test the hypothesis that fluvastatin (Flu) preserves the endothelial function by its cholesterol-lowering independent actions. Rabbits were fed a 0.5% high-cholesterol (HC) diet for 12 weeks (progression phase) and then fed the HC diet either containing or not containing Flu 2 mg/kg/day for an additional 8 weeks (treatment phase). Rabbits fed a normal diet were used as controls. Plasma total and low-density lipoprotein cholesterol concentrations did not differ during the treatment phase: Endothelium-dependent/NO-mediated relaxation (acetylcholine and A23187) was impaired in the HC diet group, whereas it was preserved in the HC plus Flu treatment group. The endothelium-independent relaxation (sodium nitroprusside) was similar between the three groups. Interestingly, aortic oxidative stress (lipid peroxides and isoprostane F(2alpha)-III contents) and NADPH oxidase component (p22phox and gp91phox) mRNA expression were increased in the HC group but not in the HC plus Flu group. The A23187-induced nitric oxide production from the aorta was increased in both HC and HC plus Flu groups. There was no significant difference in tissue endothelial-type nitric oxide synthase mRNA expression. Plaque area and intimal thickening of the aorta were significantly lowered in the HC plus Flu group. Flu treatment preserved the endothelial function associated with the decrease in markers of oxidative stress in this experiment. These beneficial endothelial effects of Flu are likely to occur independently of plasma lipid concentrations and to be mediated by its antioxidant action.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Arteriosclerosis; Cholesterol; Endothelium, Vascular; Fatty Acids, Monounsaturated; Fluvastatin; Gene Expression Regulation, Enzymologic; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipids; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Phospholipids; Rabbits

Major cardiac events are strongly associated with high levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C). The HDL-C target level (40 mg/dl) is often not achieved with statins. The aim of this study was to compare the proportions of patients achieving the HDL-C target levels after one year of treatment with statins or fibrates. Furthermore, a subgroup with low HDL-C levels during statin treatment was investigated and suggestions are made for a better management of these patients.. A survey of lipid levels, cardiovascular disease and risk factors in 120 outpatients treated with a statin or a fibrate for hyperlipidaemia (total cholesterol (TC) > 250 mg/dl or triglycerides (TG) > 200 mg/dl after diet). After one year of treatment the proportions of patients achieving the target levels for TC, LDL-C, HDL-C,TG,TC/HDL-C and LDL-C/HDL-C are compared for statins and fibrates.. The proportions of patients achieving the target lipid levels with statins or fibrates are comparable except for HDL-C. Compared to the baseline, the proportion of patients achieving the HDL-C target level of 40 mg/dl increases only by 8.3% for statins and by 42.9% for fibrates. In total, 38.5% of the statin group had low HDL-C-levels after one year of treatment. Among these patients, eight were treated with a fibrate before the statin and six were treated with a fibrate afterwards. In those 14 patients, mean HDL-C increased during fibrate treatment by 48.5% and TC/HDL-C and LDL-C/HDL-C decreased by 25.7 and 26.5%, respectively as compared with statins.. Patients with low levels of HDL-C during statin treatment had far better levels of HDL-C, TC/HDL-C and LDL-C/HDL-C with fibrates. A randomised double-blind crossover trial with simvastatin and fenofibrate has been initiated to corroborate these findings.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Clofibric Acid; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fibric Acids; Fluvastatin; Heptanoic Acids; Humans; Hyperlipidemias; Indoles; Male; Microfilament Proteins; Middle Aged; Muscle Proteins; Pravastatin; Pyrroles; Retrospective Studies

This analysis was conducted to evaluate the effect of baseline triglyceride levels on lipid and lipoprotein changes after treatment with the combination of fluvastatin and fibrates. The analysis involved pooling data from 10 studies that included 1,018 patients with either mixed hyperlipidemia or primary hypercholesterolemia. Patients received a combination of fluvastatin and a fibrate (bezafibrate, fenofibrate, or gemfibrozil) from 16 to 108 weeks. The combination of fluvastatin and a fibrate improved lipid profiles, with reductions in triglycerides, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol that were dependent on baseline triglyceride levels. The greatest triglyceride reductions were observed in patients with high baseline triglyceride levels (> or =400 mg/dl) (41%, p <0.0001). The greatest LDL cholesterol and non-HDL cholesterol reductions occurred in patients with normal baseline triglyceride levels (<150 mg/dl) (35% and 33%, respectively; p <0.0001). The combined fluvastatin-fibrate therapy was well tolerated. Two patients (0.2%) (1 patient on fluvastatin 80 mg + gemfibrozil 1,200 mg and 1 patient on fluvastatin 20 mg + fenofibrate 200 mg) had creatine kinase levels > or =10 times the upper limit of normal, 11 patients (1.1%) had an elevation in alanine transaminase >3 times the upper limit of normal, and 7 patients (0.7%) had elevations in aspartate transaminase >3 times the upper limit of normal. Combined fluvastatin-fibrate therapy takes advantage of the complementary effects of the 2 agents, with the extent of triglyceride, LDL cholesterol, and non-HDL cholesterol lowering dependent on baseline triglyceride levels. The combination of fluvastatin and fibrates was well tolerated with no major safety concerns.

Topics: Age Factors; Bezafibrate; Drug Combinations; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fluvastatin; Gemfibrozil; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipid Metabolism; Lipoproteins; Male; Middle Aged; Retrospective Studies; Sex Factors; Treatment Outcome; Triglycerides

The effects of fluvastatin on levels of urinary 8-iso-prostaglandin F2alpha (iPF2alphaIII), a marker of oxidative stress, and low-density lipoprotein (LDL) particle size in serum were investigated in patients with hypercholesterolemia. After 6 months of fluvastatin therapy, levels of urinary iPF2alphaIII decreased from 1720.1 +/- 392.0 to 539.6 +/- 75.5 pg/mg (p < 0.01), and LDL particle size increased from 24.3 +/- 0.3 to 26.5 +/- 0.2 nm (p < 0.001). These changes from the treatment of fluvastatin were not correlated with those of the serum LDL cholesterol (LDL-C) levels. The results imply that fluvastatin, with its unique antioxidant property among statins, reduces oxidative stress and increases LDL particle size simultaneously in hyperlipidemic patients.

Topics: Aged; Dinoprost; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Particle Size

Topics: Adult; Anticholesteremic Agents; Drug Administration Schedule; Fatty Acids, Monounsaturated; Female; Fluvastatin; HIV Infections; HIV Protease Inhibitors; Humans; Hyperlipidemias; Hypertriglyceridemia; Indoles; Male

To observe the changes of C-reactive protein (CRP) level and its relationship with blood lipids, and the effects of fluvastatin on CRP and the lipids in patients with hyperlipidemia.. Serum levels of cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and lipoprotein(a)[Lp(a)] were measured by enzyme assay, and plasma CRP level by immunonephelometry before and after fluvastatin treatment (20 mg/d for 4 weeks) in patients with hyperlipidemia.. CRP levels were above normal in 90.3% hyperlipidemia cases in spite of the various accompanying diseases. Fluvastatin treatment significantly reduced TC (-7.49%), TG (-14.32%), LDL (-13.88%), VLDL (-18.48%) and TC/HDL(-13.50%) levels (P<0.01), and also brought down Lp(a) concentration (-13.81%). CRP levels was very effectively reduced after the treatment (-15.92%, P<0.001). No association between basal CRP levels and basal lipids and Lp(a) concentrations was observed. Positive correlation of CRP, however, was observed after fluvastatin treatment with TC/HDL (r=0.62, P=0.041) and Lp(a) (r=0.320, P=0.011), while inverse relations were noted between CRP and HDL (r=-0.288, P=0.023).. CRP levels increases markedly in patients with hyperlipidemia, a fact that is independent of the accompanying diseases. In addition to modulating blood lipid levels, fluvastatin also reduces CRP level, the latter possibly serving as an independent predictive factor for atherosclerotic cardiovascular diseases and also as an indicator for estimating the effectiveness of the treatment.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; C-Reactive Protein; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Lipids; Male; Middle Aged

Topics: Adult; Aged; Anticholesteremic Agents; Creatine Kinase; Delayed-Action Preparations; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Hyperlipidemias; Indoles; Male; Middle Aged

The in vivo antioxidant effect of fluvastain, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was investigated using Watanabe heritable hyperlipidemic (WHHL) rabbits subjected to nicotine-free cigarette smoke extracts as oxidative stress. Fluvastatin was given orally at doses of 10 and 30 mg/kg per day for 5 months. The cigarette smoke extracts were prepared by bubbling the gas phase of smoke into phosphate-buffered saline and was injected daily into the rabbit ear vein. The rabbits chronically treated with the cigarette smoke extracts showed an increase in plasma lipid peroxide levels, estimated as thiobarbituric acid-reactive substances. Oxidative modification of plasma low-density lipoprotein (LDL) was assessed by anion-exchange high-performance liquid chromatographic analysis, LDL susceptibility to oxidation, LDL incorporation into macrophages and thiobarbituric acid-reactive substances levels in LDL. Treatment with fluvastatin significantly reduced these effects induced by the cigarette smoke extracts in a dose-related manner and exerted a cholesterol-lowering effect. At the end of the experiment, the cigarette smoke extracts caused accumulation of cholesteryl ester in the thoracic aorta, while fluvastatin significantly prevented this accumulation. These results indicate that fluvastatin can exert an antioxidant effect in vivo, with a strong effect on oxidative stress such as smoking, a major risk factor of atherosclerosis.

Topics: Animals; Antioxidants; Aorta, Thoracic; Body Weight; Cholesterol; Cholesterol Esters; Cholesterol, LDL; Chromatography, High Pressure Liquid; Copper; Coronary Vessels; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hyperlipidemias; In Vitro Techniques; Indoles; Lipoproteins, LDL; Macrophages, Peritoneal; Male; Mice; Oxidation-Reduction; Oxidative Stress; Rabbits; Renal Artery; Thiobarbituric Acid Reactive Substances

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

Acute coronary syndromes often result from rupture of vulnerable plaques. The collagen content of plaques probably regulates their stability. This study tested whether HMG-CoA reductase inhibitors (statins) alter interstitial collagen gene expression or matrix metalloproteinase (MMP) levels in rabbit atheroma.. We administered equihypocholesterolemic doses of pravastatin (a hydrophilic statin, 50 mg. kg(-1). d(-1), n=9), fluvastatin (a cell-permeant lipophilic statin, 20 mg. kg(-1). d(-1), n=10), or placebo (n=10) to mature Watanabe heritable hyperlipidemic rabbits for 52 weeks. The fluvastatin group achieved a much higher peak plasma concentration (23.7 micromol/L) than did the pravastatin group (1.3 micromol/L) under these conditions. Immunohistochemistry revealed that MMP-1, MMP-3, and MMP-9 expression by macrophages in the intima was lower in both the pravastatin and fluvastatin groups than in the placebo group, whereas there was no difference in macrophage numbers. Numbers of intimal smooth muscle cells (SMCs) (identified by immunohistochemistry) and expression of type I procollagen mRNA (detected by in situ hybridization), however, were significantly higher in the pravastatin group than in the fluvastatin group. Treatment with pravastatin, but not fluvastatin, preserved interstitial collagen content in vivo (detected by picrosirius red polarization). In vitro, fluvastatin, but not pravastatin, decreased numbers of rabbit and human aortic SMCs without altering procollagen I mRNA expression.. This study showed that statins can reduce MMP expression in atheroma and that cell-permeant statins can decrease SMC number and collagen gene expression in vivo.

Topics: Animals; Arteriosclerosis; Azo Compounds; Cell Division; Cells, Cultured; Collagen; Coloring Agents; Fatty Acids, Monounsaturated; Fluvastatin; Gene Expression Regulation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Immunohistochemistry; Indoles; Lipids; Macrophages; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Muscle, Smooth; Pravastatin; Procollagen; Rabbits; RNA, Messenger

Topics: Bezafibrate; C-Reactive Protein; Coronary Disease; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Models, Statistical

Increased vascular endothelial cell growth factor (VEGF) may be important in cardiovascular pathophysiology (perhaps relating to angiogenesis and collateral vessel development) and binds target endothelium via receptors such as Flt-1. We hypothesized that there would be increased levels of plasma VEGF and Flt-1 in patients with atherosclerosis and others with hyperlipidemia compared with controls, and a reduction in these factors with 3 months of lipid-lowering therapy. Twenty patients with uncomplicated hyperlipidemia but no atherosclerosis, 20 patients with hyperlipidemia plus clear atherosclerosis, and 40 matched controls were studied. Plasma VEGF was higher in patient groups than in healthy controls (p <0.01), but Flt-1 was not significantly altered. After lipid-lowering therapy, patients with uncomplicated hyperlipidemia had significantly reduced total cholesterol and VEGF (all p <0.05) but no significant change in Flt-1. Lack of a significant correlation between the von Willebrand factor and VEGF suggests the latter is unrelated to endothelial damage. Plasma VEGF that increases in patients with uncomplicated hyperlipidemia free of major underlying atherosclerosis and in patients with hyperlipidemia plus established atherosclerosis is reduced by successful lipid-lowering treatment. These findings may have implications for the pathophysiology and treatment of hyperlipidemia and atherosclerosis, and suggest an alternative mechanism (i.e., modulation of angiogenesis) by which lipid-lowering therapy may reduce cardiovascular events beyond lipid reduction alone.

Topics: Anticholesteremic Agents; Arteriosclerosis; Cholesterol; Endothelial Growth Factors; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fluvastatin; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lymphokines; Male; Middle Aged; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; von Willebrand Factor

HMG-CoA reductase inhibitors ("statins") have become the drug class of choice for the treatment of hyperlipidemia. Six product brands encompassing 20 dosage strengths have been available during the past two years. The objective of this review is to describe dosing trends for the six statin brands and to determine if and how these trends vary among managed care plans as a function of product market share.. Utilization of HMG-CoA reductase inhibitors was examined using the NDC Health Information Services (Phoenix, Ariz.) database for the two-year period ending December 2000. This database contains unit dispensing data at the dosage-strength level for 1,079 managed care plans. Trends in market share, mean daily dose, and dosage distribution of the six current statin brands were examined. The relationship of market share to mean dose was also examined for each brand.. Market share decreased for all statin brands during the two-year period, except for the two newest entries, atorvastatin (up 9.7 share points) and cerivastatin (up 4.6 share points). The mean dose of all statins increased during the two-year period. A statistically significant negative correlation between market share and mean dose was found for atorvastatin and a positive correlation was found for fluvastatin (P < 0.01). Furthermore, atorvastatin share was significantly correlated to lower mean doses of all other statin brands. That is, higher use of atorvastatin was associated with lower doses of all statin products.. In developing a cost-management strategy, managed care organizations should take historical and anticipated market-share changes and dose-mix changes into account along with the product's clinical efficacy and total cost of care.

Topics: Anticholesteremic Agents; Atorvastatin; Databases, Factual; Drug Costs; Drug Utilization Review; Fatty Acids, Monounsaturated; Fluvastatin; Health Care Sector; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lovastatin; Managed Care Programs; Pravastatin; Pyridines; Pyrroles; Simvastatin; United States

1. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to decrease the oxidizability of plasma lipids in hyperlipidaemic subjects. In order to elucidate one of the mechanisms of this in vivo, we investigated the effects of fluvastatin and pravastatin on the decreased turnovers of reduced glutathione (GSH) and ascorbic acid (AA) in Watanabe heritable hyperlipidaemic (WHHL) rabbits. 2. These drugs (30 mg/kg per day) equally decreased plasma levels of lipids after a 4 week treatment period. However, only fluvastatin significantly decreased thiobarbituric acid-reactive substances, which were increased in the plasma of WHHL. 3. Although these drugs did not affect the steady state levels of total glutathione and low molecular weight thiols in the liver and kidney, fluvastatin markedly normalized the rate of GSH turnover in these tissues, as determined by using L-buthionine-(S,R)-sulphoximine, a specific inhibitor of GSH synthesis. 4. Fluvastatin also increased the clearance of AA from the circulation in WHHL. 5. These results suggest that, in addition to its hypolipidaemic action, fluvastatin has the potential to improve the turnover of anti-oxidants, which is closely related to the amelioration of the redox status in the body.

Topics: Animals; Anticholesteremic Agents; Antimetabolites; Ascorbic Acid; Buthionine Sulfoximine; Cholesterol; Fatty Acids, Monounsaturated; Fluvastatin; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney; Liver; Male; Oxidation-Reduction; Phospholipids; Pravastatin; Rabbits; Thiobarbituric Acid Reactive Substances; Triglycerides

Combinations of gemfibrozil and a 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase inhibitor show promise in treating mixed lipid abnormalities. However, concern regarding the risk of myopathy and hepatic toxicity has limited the use of this combination. To determine the long-term safety and efficacy of this combination, we prospectively identified all patients placed on a combination of gemfibrozil and any HMG reductase inhibitor.. Pravastatin, simvastatin, fluvastatin, lovastatin, or atorvastatin at incremental doses was combined with gemfibrozil (600 mg twice daily). Lipid profiles, creatine kinase levels, and aminotransferase levels were monitored. Two hundred fifty-two patients with established atherosclerosis receiving combination therapy for a mean of 2.36 +/- 1.52 years spanning a total of 593.6 patient-years were monitored.. In 148 patients, gemfibrozil was started before an HMG was added. The pretreatment total cholesterol level fell from 222 +/- 34 mg/dL to 181 +/- 26 mg/dL (P <.001) on combination therapy. HDL cholesterol level rose from 30 +/- 5 mg/dL to 36 +/- 7 mg/dL (P <.01), triglyceride level fell from 361 +/- 141 mg/dL to 212 +/- 101 mg/dL (P <.03). The ratio of total cholesterol to HDL fell from 7.6 +/- 1. 7 to 5.3 +/- 1.6 (P <.001). In 104 patients an HMG was begun before gemfibrozil was added. Pretreatment total cholesterol level fell from 246 +/- 54 mg/dL to 192 +/- 40 mg/dL on combination therapy (P <.01). HDL level rose from 33 +/- 9 mg/dL to 38 +/- 9 mg/dL (P <.03) and triglyceride level fell from 314 +/- 183 mg/dL to 183 +/- 93 mg/dL (P <.001). The ratio of total cholesterol to HDL fell from 7.9 +/- 3.6 to 5.2 +/- 1.4 (P <.001). In both groups the lipid profile on combination therapy was significantly better than that obtained on single-agent therapy. One episode of myopathy (0.4%) and one episode of aminotransferase level elevation (0.4%) of greater than 3 times upper limit of normal occurred. Both resolved with cessation of therapy without consequence.. Combinations of gemfibrozil and an HMG, compared with either agent alone, results in improved long-term control of lipid abnormalities in mixed lipid disorders. The low incidence of toxicity permits the use of combination therapy in patients at high risk of atherosclerotic complications.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gemfibrozil; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipids; Lovastatin; Male; Middle Aged; Pravastatin; Prospective Studies; Pyrroles; Simvastatin; Time Factors; Treatment Outcome

We evaluated the use of combination therapy (ciprofibrate 100 mg or bezafibrate 400 mg plus fluvastatin 40 mg) in 23 patients (n = 13 in the ciprofibrate group) with established cardiovascular disease. Both treatments achieved a significant (P< or =0.01) decrease in the total cholesterol (TC) (32 and 21%), triglycerides (TG) (53 and 46%) and low-density lipoprotein (LDL) (36 and 26%) levels and the TC/high-density lipoprotein (HDL) (42 and 31%) and LDL/HDL (46 and 35%) ratios. HDL levels were increased (19% for both treatment groups), but this rise only achieved significance (P=0.01) in the ciprofibrate group. Although the two patient groups were not strictly matched, the reduction in serum TC and LDL levels was greater with ciprofibrate (32 and 36%, respectively; P< or =0.001) than with bezafibrate (21 and 26%, respectively; P< or =0.01). There was a significant reduction in plasma fibrinogen levels (36.4 and 13.5% in the ciprofibrate and bezafibrate group, respectively). None of the patients reported myalgia or had abnormal creatine kinase activity or liver function tests. Combination therapy is worth considering in high-risk patients because of the advantages associated with this option. Combination therapy is competitively priced when compared with high doses of statins. An end-point-based trial is needed.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Bezafibrate; Cardiovascular Diseases; Clofibric Acid; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fibric Acids; Fluvastatin; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Male; Middle Aged; Pilot Projects; Treatment Outcome

Topics: Adult; Anticholesteremic Agents; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Infant, Newborn; Kidney Transplantation; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Prenatal Exposure Delayed Effects

The present study was conducted in order to examine the role of low-density lipoprotein (LDL)-receptor activity in very-low-density lipoprotein (VLDL) triglyceride metabolism in vivo. Fructose-feeding (10% in drinking water) for 2 weeks resulted in elevated plasma triglyceride in heterozygote of Watanabe heritable hyperlipidemic (WHHL) rabbit (WHHLH) associated with suppressed fractional catabolic rate (FCR) of plasma triglyceride, whereas Japanese white (JW) rabbit with normal LDL receptor activity showed no remarkable change in plasma triglyceride turnover after fructose-feeding, suggesting an involvement of LDL receptor activity on triglyceride metabolism. Thereafter, in order to stimulate cellular LDL receptor activity, fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor, was administered orally (1.52 +/- 0.26 mg/kg) to fructose-fed WHHLH. Significant suppression of triglyceride secretion rate (TGSR) was observed after treatment. However, since plasma triglyceride level was markedly suppressed, FCR of plasma triglyceride was significantly elevated by fluvastatin. Thus, it is speculated from the present data that LDL receptor activity is significantly involved in VLDL triglyceride metabolism in rabbits.

Topics: Animals; Fatty Acids, Monounsaturated; Fluvastatin; Fructose; Heterozygote; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipase; Lipoprotein Lipase; Lipoproteins, VLDL; Rabbits; Receptors, LDL; Triglycerides

The effects of fluvastatin sodium (CAS 93957-55-2, XU 62-320), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the smooth muscle cells in the atherosclerotic plaques of Watanabe heritable hyperlipidemic (WHHL) rabbits, a low density lipoprotein (LDL) receptor deficient animal model, were examined. Fluvastatin was administered to WHHL rabbits for 32 weeks at a dose of 50 mg/kg of body weight. The control WHHL rabbits were administered distilled water as placebo. Compared to the control group, the total cholesterol levels in the sera, very low density lipoprotein, intermediate density lipoprotein, and LDL decreased by 34%, 72%, 63%, and 25%, respectively. Although the surface lesion area of the aorta in the treated group was not different from that in the control group, intimal thickening in the treated group was significantly lower than that in the control group. Of the lesional components of atherosclerosis, the relative area of smooth muscle cells, collagen fibers, and extracellular lipid deposits in the treated group decreased significantly. It is concluded that fluvastatin decreased in the smooth muscle cell content of the atherosclerotic plaques and delayed progression of the aortic atherosclerosis in addition to the potent hyperlipidemic effect.

Topics: Animals; Antibodies, Monoclonal; Arteriosclerosis; Cholesterol; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Immunohistochemistry; Indoles; Lipids; Lipoproteins; Male; Muscle, Smooth, Vascular; Rabbits; Receptors, LDL

Topics: Anticholesteremic Agents; Arteriosclerosis; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hypercholesterolemia; Hyperlipidemias; Indoles

Previous investigations revealed that hypolipidaemic treatment of patients with IHD in the Czech Republic is inadequate. Patients after revascularization operations are discharged from cardiosurgical departments without suitable medication and moreover the values of the lipid spectrum are affected by the surgical intervention. The objective of the investigation was to evaluate the indication of hypolipidaemic treatment during hospitalization or later during check-up examinations by attending physicians. The authors evaluated retrospectively 100 patients after revascularization operations of the heart discharged without hypolipidaemic treatment and 40 patients treated with fluvastatin because of the lipid values before surgery. Using questionnaires it was revealed that in the group without pharmacological intervention in 36% patients the lipid levels were checked and hypolipidaemic treatment was started in 14% of the patients. In the patients with pharmacological treatment 100% adherence to treatment and improvement of the lipid spectrum was found similarly as in comparable trials. Fluvastatin treatment was well tolerated. In the authors view hypolipidaemic treatment after revascularization should be started before discharge from hospital with regard to preoperative results of the lipid spectrum.

Topics: Anticholesteremic Agents; Coronary Artery Bypass; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Lipids; Male; Middle Aged

Hyperlipidaemia of 18 male and 20 female patients following successful renal transplantation was treated with daily 20 mg fluvastatin (Lescol) for 12 weeks. The patients were several months after transplantation, and their total cholesterol levels exceeded 6.5 mmol/l following an 8-week diet. The effect of fluvastatin on the levels of total cholesterol, HDL, LDL, triglyceride, Apo A1 and Apo B, as well as of lipoprotein(a) was examined. Furthermore, changes of the renal function (GFR-urea, creatinine, uric acid) and hepatic function (bilirubin, GOT, GPT, CPK, ALP) were followed up, together with the body weight and blood pressure. The results of the examinations are summarized as follows: Fluvastatin may be administered effectively and without side effects in a daily dose of 20 mg in appropriately selected renal transplant patients. The average total cholesterol values, which were 7.91 mmol/l in men and 7.78 mmol/l in women following the diet, were reduced by 22-25% (p < 0.001) after 6 and 12 weeks, respectively, of fluvastatin treatment. The levels of LDL also decreased significantly (p < 0.001): in response to a 20 mg evening dosage, reduction of more than 25% was observed in 78% of men and 65% of women. Reductions of the Apo B levels were more pronounced in the females (18.3% men vs. 21.2% women). The ratio C/HDL-C decreased both in men (from 5.49 to 4.19) and in women (from 4.83 to 4.02). The ratio Apo B/Apo A1 also decreased (men: from 0.86 to 0.73, women: from 0.73 to 0.66). The concentrations of HDL and Apo A1 did not increase significantly, the reductions in the levels of triglyceride and lipoprotein(a) were not considerable either. An increase in the levels of hepatic enzymes and CPK was not encountered during the administration of fluvastatin. In two patients the levels of serum bilirubin increased by 2-4 micromol/l. Three patients complained about temporary myalgias of the sacroiliac or lumbar region which, however, were not accompanied by elevated CPK levels. The monitored levels of cyclosporine, urea and creatinine did not increase significantly during the 12 weeks of treatment. Two patients had temporary gastric complaints.

Topics: Adult; Aged; Anticholesteremic Agents; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Kidney Transplantation; Lipids; Male; Middle Aged

Topics: Anticholesteremic Agents; Capsules; Cholesterol; Cholesterol, LDL; Enzyme Inhibitors; Fatty Acids, Monounsaturated; Fluvastatin; Gels; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Indoles; Liver; Receptors, LDL

To determine if patients treated with HMG-CoA reductase inhibitors have their LDL cholesterol levels at or below the levels recommended by the National Cholesterol Education Program (NCEP) and if patients on these medications are monitored for potential toxicity.. Ninety patients from the VA Medical Center in San Francisco were randomly selected in this retrospective analysis. All patients were taking a HMG-CoA reductase inhibitor as monotherapy for treatment of high blood cholesterol for a minimum of 1 year. Medical charts and laboratory and pharmacy computer databases were utilized to gather information regarding the patients' medical history, treatment history, relevant laboratory tests, and medication refill profile.. The majority of patients, 73%, were secondary prevention patients. Only 33% of the 90 subjects met the LDL cholesterol goal recommended by the NCEP. For the secondary prevention patients, only 24% met goal LDL. Even when the stringency of the NCEP guidelines was reduced by 20% (goal LDL < 120 mg/dL), 50% of the secondary prevention patients were still inadequately treated. Only 2 of the 90 patients were on maximal dosage regimens. Sixty-seven percent of patients had annual lipid panels and 49% had annual liver panels. Forty-five percent of patients followed by nonphysicians met goal LDL while only 29% and 31% of patients followed by attending physicians and residents/fellows met goal LDL, respectively. In addition, patients followed by nonphysicians were monitored more closely for efficacy and toxicity of the medications.. Based on the current NCEP recommendations, patients on monotherapy with HMG-CoA reductase inhibitors are often inadequately treated. Only 33% of the patients evaluated at our institution were at or below the NCEP recommended LDL cholesterol levels and less than half of the patients were adequately monitored for hepatotoxicity.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Cholesterol, LDL; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lovastatin; Male; Middle Aged; Patient Selection; Pravastatin; Retrospective Studies; Treatment Outcome

Topics: Aged; Anticholesteremic Agents; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gemfibrozil; Humans; Hyperlipidemias; Hypolipidemic Agents; Hypothyroidism; Indoles; Lovastatin; Male; Middle Aged; Neuromuscular Diseases; Simvastatin; Thyroxine

To assess the efficacy and safety of fluvastatin in hypercholesterolemic, cyclosporine-treated, renal transplant recipients, and to determine whether concomitant steroid therapy in such patients alters the lipid-lowering effects of fluvastatin.. An open-label, prospective, parallel study was performed in 20 cyclosporine-treated renal transplant recipients with hypercholesterolemia defined by a low-density lipoprotein (LDL) concentration greater than 160 mg/dL or a total cholesterol/high-density lipoprotein (HDL) concentration ratio greater than 5.0. Lipid profiles were measured before and 1 month after treatment with fluvastatin 20 mg/d. Lipid profiles in a group of patients receiving concomitant therapy with prednisone (n = 12) were compared with those of patients who had not received steroids for at least 6 months (n = 8).. The Renal Transplant Clinic at University Hospitals of Cleveland.. The main outcome measures were serum concentrations of total cholesterol, LDL, HDL, and triglycerides. Treatment failure was defined by LDL concentrations persistently above 160 mg/dL after 1 month of fluvastatin therapy. Safety was assessed clinically and by serial measurements of liver enzymes and creatine phosphokinase.. LDL concentrations decreased significantly in both the steroid-treated and steroid-free groups after 1 month of fluvastatin therapy. There was no significant change in HDL concentrations or serum triglycerides in either group. Treatment failure was more common in patients receiving steroids (4/12 patients) than in steroid-free patients (1/8 patients). After 1 month of therapy, LDL cholesterol was significantly lower in the steroid-free group (126 +/- 18 mg/dL) than in the steroid-treated group (147 +/- 23 mg/dL) (p < 0.05). There was no clinical or laboratory evidence of myonecrosis in either group.. Low dosages of fluvastatin appear to be safe in cyclosporine-treated renal transplant recipients. Steroid-free patients exhibit a response to fluvastatin that is qualitatively similar to that of steroid-treated patients, consisting of a significant decrease in LDL concentrations and no change in HDL or serum triglyceride concentrations.

Topics: Anticholesteremic Agents; Cholesterol, HDL; Cholesterol, LDL; Cyclosporine; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glucocorticoids; Humans; Hypercholesterolemia; Hyperlipidemias; Immunosuppressive Agents; Indoles; Kidney Transplantation; Male; Middle Aged; Prednisone; Prospective Studies

The effects of fluvastatin sodium (XU62-320), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on plasma cholesterol and triacylglycerol levels were investigated using homozygous Watanabe-heritable hyperlipidemic (WHHL) rabbit, an LDL-receptor-deficient animal which expresses a hepatic LDL receptor activity less than 5% that of control rabbits. Plasma levels of total, VLDL- and LDL-cholesterol were decreased profoundly after oral administration of fluvastatin at a dose of 50 mg/kg per day for 4 weeks. Plasma triacylglycerol levels were not affected by fluvastatin. Hepatic HMG-CoA reductase activity increased by 3-fold and hepatic LDL receptor activity increased by only 3.7-fold, as calculated by Scatchard plot analysis, with fluvastatin administration for 4 weeks, and the hepatic mRNA level for the rabbit LDL receptor was increased by 3-fold. Combined administration of fluvastatin (50 mg/kg per day) and cholestyramine, a bile acid sequestrant resin, at a level of 2% of the diet for 4 weeks more profoundly decreased plasma total, VLDL- and LDL-cholesterol levels with induction of hepatic cholesterol 7 alpha-hydroxylase and no further induction of the hepatic LDL receptor. Plasma triacylglycerol levels were increased by the combination treatment. These results suggest that high dose of fluvastatin sodium is effective in lowering plasma cholesterol levels in homozygous WHHL rabbits through the shared mechanisms involving decrease in production and secretion of cholesterol from the liver and the induction of hepatic LDL receptor. Additional effect of cholestyramine on decrease in plasma cholesterol levels seems to be due to the further decrease in hepatic cholesterol secretion by up-regulation of hepatic cholesterol 7 alpha-hydroxylase.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Cholestyramine Resin; Fatty Acids, Monounsaturated; Fluvastatin; Homozygote; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Liver; Microsomes, Liver; Rabbits; Receptors, LDL; RNA, Messenger; Triglycerides

The hypolipidemic effects of fluvastatin sodium (XU 62-320, CAS 93957-55-2), a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, were examined. Fluvastatin sodium was administered to Watanabe heritable hyperlipidemic (WHHL) rabbits, a low density lipoprotein (LDL) receptor deficient animal model, for 6 weeks at doses of 12.5 mg/kg, 25 mg/kg, and 50 mg/kg. Total cholesterol levels in serum, in very low density lipoproteins (VLDL), in intermediate density lipoprotein, and in LDL decreased dose-dependently. In the 50 mg/kg group, cholesterol reduction in each of the aforementioned segments was 50%, 91%, 94% and 33%, respectively. The secretion rate of VLDL-cholesterol, as determined by intravenous injection of Triton WR-1339, also decreased in a dose-dependent manner, showing a reduction of 16% (p < 0.05) in the 50 mg/kg group. In addition, the cholesterol content of newly-secreted VLDL also decreased dose-dependently. These results indicate that fluvastatin sodium has a potent hypolipidemic effect, and suggest that one of the mechanisms responsible for the reduction of serum cholesterol may be the suppression of VLDL-cholesterol secretion.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Fluvastatin; Hyperlipidemias; Indoles; Lipids; Lipoproteins, VLDL; Rabbits; Receptors, LDL

Topics: Animals; Anticholesteremic Agents; Coronary Disease; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hyperlipidemias; Indoles; Risk Factors