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

The use of statins for cardiovascular disease prevention is clearly supported by clinical evidence. However, in January 2014 the U.S. Food and Drug Administration released an advice on statin risk reporting that "statin benefit is indisputable, but they need to be taken with care and knowledge of their side effects". Among them the by far most common complication is myopathy, ranging from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. This class side effect appears to be dose dependent, with more lipophilic statin (i.e., simvastatin) carrying a higher overall risk. Hence, to minimize statin-associated myopathy, clinicians should take into consideration a series of factors that potentially increase this risk (i.e., drug-drug interactions, female gender, advanced age, diabetes mellitus, hypothyroidism and vitamin D deficiency). Whenever it is appropriate to stop statin treatment, the recommendations are to stay off statin until resolution of symptoms or normalization of creatine kinase values. Afterwards, clinicians have several options to treat dyslipidemia, including the use of a lower dose of the same statin, intermittent non-daily dosing of statin, initiation of a different statin, alone or in combination with nonstatin lipid-lowering agents, and substitution with red yeast rice.

Topics: Age Factors; Aged; Aged, 80 and over; Anticholesteremic Agents; Colesevelam Hydrochloride; Creatine Kinase; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Muscular Diseases; Myalgia; Rhabdomyolysis; Risk Assessment; Risk Factors; Rosuvastatin Calcium; Sex Factors; Vitamin D Deficiency

This pooled analysis of 30 completed clinical trials assessed the efficacy and safety profile in reducing cardiovascular disease (CVD) risk of fluvastatin in the treatment of dyslipidemia in patients with and without the metabolic syndrome (metS).. Data from 30 double-blind, randomized, placebo-controlled or fluvastatin-controlled trials with > or =6 weeks of active treatment and daily fluvastatin doses of 20, 40, and 80 mg were pooled. Patients received fluvastatin or placebo. Linear contrasts from an analysis of covariance model containing factors for trial and treatment group (immediate-release fluvastatin 20, 40, 80 mg; extended-release fluvastatin 80 rag; or placebo), and using the baseline value as covariate, were used to compare the percentage changes from baseline to the first postbaseline assessment of all lipid parameters. A Cox regression analysis compared the all-fluvastatin group to the placebo group with regard to the time to occurrence of clinical end points from 5 pooled studies, each with a mean treatment duration >1 year wherein clinical end points were reviewed by an adjudication committee. These analyses were performed separately for patients with and without metS.. This pooled analysis included data from 7043 patients (4095 men, 2948 women; all-fluvastatin group with and without metS, 2529 and 2052 patients, respectively; placebo group with and without metS, 1514 and 948 patients, respectively). Patients with metS in the pooled fluvastatin group had a greater mean reduction in triglyceride levels (24.1% vs 6.7%), a greater mean increase in high-density lipoprotein cholesterol levels (10.3% vs -0.6%), and a similar mean reduction in low-density lipoprotein cholesterol levels (26.8% vs 26.7%) compared with the subgroup of patients without metS. Treatment with fluvastatin was associated with a significantly lower incidence of major adverse cardiovascular events (MACEs) (16.4% vs 22.0%) and an increase in the time to first MACE in patients with metS compared with placebo (hazard ratio = 0.728; P = 0.001). The incidences of adverse events, particularly those of concern (ie, myalgia and/ or increased blood creatine phosphokinase, alanine aminotransferase, and/or aspartate aminotransferase) with lipid-lowering therapy, were statistically similar between the patients who received fluvastatin and those who received placebo in the 2 subgroups.. The results from this pooled analysis found that fluvastatin was effective in reducing CVD risk in the treatment of dyslipidemia in these patients with metS.

Topics: Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Indoles; Male; Metabolic Syndrome; Middle Aged; Triglycerides

Chronic kidney disease (CKD) is extremely common in adults, although often undiagnosed and thus untreated. Cardiovascular disease is the leading cause of death among patients with CKD and reducing its risk in this population is an important priority. Dyslipidemia is almost always present when proteinuria is above 3 gr/24 hours. Roughly two thirds of all patients with end-stage renal failure and kidney transplants suffer from dyslipidemia and should receive lipid-lowering therapy, as suggested by recent Afssaps (French drug agency) and NKF-K/DOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. We reviewed recent studies on efficacy, tolerability and prescription recommendations of statins in CKD and renal transplant patients.. We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population.. The efficacy of statins in decreasing total cholesterol and LDL-cholesterol levels in dialysis and renal transplant patients is similar to that in the general population. On the other hand, large-scale randomized clinical trials among CKD (4D) and renal transplant (ALERT) patients do not demonstrate that statins significantly decrease rates of cardiovascular disease. They have a beneficial effect on proteinuria and lower the rate of kidney function deterioration in patients with dyslipidemia. Early introduction of a statin in transplant patients did not lead to improved kidney function or prevent loss of the graft. Although most statins are not excreted by the kidneys, the dosage of some must be adapted in CKD patients because of pharmacokinetic modifications induced by renal impairment.. Statins at appropriately adapted doses have the same efficacy in CKD patients as in subjects with normal kidney function, and tolerance is not a problem. Their effectiveness in cardiovascular prevention in this population has not been demonstrated to date. Results about statin-induced kidney protection are encouraging but further and more specific studies are needed.

Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Dyslipidemias; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Graft Rejection; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Kidney Failure, Chronic; Liver Transplantation; Middle Aged; Pravastatin; Primary Prevention; Prospective Studies; Proteinuria; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Factors; Rosuvastatin Calcium; Simvastatin; Sulfonamides; Time Factors

Topics: Cardiovascular Diseases; Cholesterol; Dyslipidemias; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Indoles; Kidney Diseases; Kidney Transplantation; Lipid Metabolism; Practice Guidelines as Topic; Renal Dialysis; Risk Factors; Triglycerides

In comparison to the general population, individuals with chronic kidney failure experience an increased risk for atherosclerotic cardiovascular disease attributed predominantly to pronounced abnormalities in lipid metabolism. The emerging consensus is that patients with chronic kidney failure should be treated aggressively for dyslipidemia. Statins reduce the risk of cardiovascular disease in a range of at-risk patients; this class of lipid-lowering drugs should be considered first-line treatment of dyslipidemia observed in renal disease patients. Although the statins share a common lipid-lowering effect, there are differences within this class of drugs. The statins differ in their pharmacokinetic effects, drug interaction profiles, and risk of myotoxicity. This article characterizes the dyslipidemia observed in the renal failure setting and reviews the therapeutic considerations involved in selecting among the statins. Lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin are the available statins in the United States.

Topics: Atorvastatin; Comorbidity; Dyslipidemias; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Lovastatin; Pravastatin; Pyrimidines; Pyrroles; Rosuvastatin Calcium; Simvastatin; Sulfonamides

Dyslipidemia is a risk factor for premature cardiovascular morbidity and mortality in renal transplant recipients (RTRs). Pharmacotherapy with mTOR inhibitors aggravates dyslipidemia, thus necessitating lipid-lowering therapy with fluvastatin, pravastatin, or atorvastatin. These agents may not sufficiently lower lipid levels, and therefore, a more potent agent like rosuvastatin maybe needed.. We have aimed to assess the lipid-lowering effect of rosuvastatin as compared with fluvastatin in RTR receiving everolimus. Safety was assessed as the pharmacokinetic (PK) interaction potential of a rosuvastatin/everolimus combination in RTR. A 12-hour everolimus PK investigation was performed in 12 stable RTR receiving everolimus and fluvastatin (80 mg/d). Patients were then switched to rosuvastatin (20 mg/d), and a follow-up 12/24-hour PK investigation of everolimus/rosuvastatin was performed after 1 month. All other drugs were kept unchanged.. In RTR already receiving fluvastatin, switching to rosuvastatin further decreased LDL cholesterol and total cholesterol by 30.2±12.2% (P<0.01) and 18.2±9.6% (P<0.01), respectively. Everolimus AUC0-12 was not affected by concomitant rosuvastatin treatment, 80.3±21.3 μg*h/L before and 78.5±21.9 μg*h/L after, respectively (P=0.61). Mean rosuvastatin AUC0-24 was 157±61.7 ng*h/mL, approximately threefold higher than reported in the literature for nontransplants. There were no adverse events, and none of the patients had or developed proteinuria.. Rosuvastatin showed a superior lipid-lowering effect compared to fluvastatin in stable RTR receiving everolimus. The combination of everolimus/rosuvastatin seems to be as safe as the everolimus/fluvastatin combination.

Topics: Aged; Biomarkers; Cytochrome P-450 CYP3A; Drug Interactions; Drug Substitution; Dyslipidemias; Everolimus; Fatty Acids, Monounsaturated; Female; Fluorobenzenes; Fluvastatin; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Indoles; Kidney Transplantation; Lipids; Male; Middle Aged; Norway; Phenotype; Prospective Studies; Pyrimidines; Rosuvastatin Calcium; Sirolimus; Sulfonamides; Treatment Outcome

Dyslipidemia is a common complication of chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality of CKD patients.. The aim of the present study was to determine whether fluvastatin, which is mostly characterized by its pleiotropic anti-oxidant effects, has renoprotective effects in dyslipidemic patients with CKD.. In 43 dyslipidemic patients with CKD taking fluvastatin 10 mg/day, 20 mg/day or 30 mg/day, renal functions as well as lipid profiles were assessed.. After 3 months of treatment with fluvastatin, LDL-cholesterol level significantly decreased. Serum creatinine level, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), urinary liver-type fatty acid binding protein (L-FABP) level and urinary 8-hydroxydeoxyguanosine (8-OHdG) level did not change in overall patients. However, in patients with microalbuminuria (baseline UAE ≥ 30 mg/g·creatinine; n = 23), the UAE significantly decreased [2.43 ± 0.67 to 1.98 ± 0.80 log(mg/g·creatinine), p = 0.01]. In patients with high L-FABP group (baseline L-FABP ≥ 11 µg/g·creatinine; n = 18), the urinary L-FABP level was significantly decreased (1.52 ± 0.45 to 1.26 ± 0.43 µg/g·creatinine, p < 0.01). In the limited 23 patients with microalbuminuria, the L-FABP level was significantly decreased [1.20 ± 0.62 to 1.03 ± 0.49 log(µg/g·creatinine), p = 0.042], although the LDL-cholesterol level (139 ± 28 to 129 ± 23 mg/dL, p = 0.08) only showed a tendency to decrease. The 8-OHdG level also was significantly decreased (13.6 ± 9.6 to 9.8 ± 3.8 ng/g·creatinine, p = 0.043). In the overall patients, changes in the values for UAE and urinary L-FABP were not correlated with the changes in LDL-levels.. Fluvastatin reduces both UAE and the urinary L-FABP level, and thus, has renoprotective effects, independent of its lipid lowering effects in dyslipidemic patients with CKD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Albuminuria; Cholesterol, LDL; Creatinine; Deoxyguanosine; Dyslipidemias; Fatty Acid-Binding Proteins; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Renal Insufficiency, Chronic; Treatment Outcome

The treatment effects of rosuvastatin on arterial stiffness were assessed and compared to those of fluvastatin in high-risk Japanese patients with dyslipidemia in a primary prevention group.. Patients were randomly assigned to either 2.5-5 mg/day of rosuvastatin (Group A) or 20-40 mg/day of fluvastatin (Group B) and followed up for 12 months. In Group A (n=38), there was a progressive reduction in brachial-ankle pulse wave velocity (baPWV) along with a decrease in the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (L/H) ratio and high-sensitivity C-reactive protein (hsCRP), and the change in baPWV correlated significantly with that of the L/H ratio and that of hsCRP after rosuvastatin treatment. In Group B (n=37), although fluvastatin achieved a significant improvement in baPWV, L/H ratio, and hsCRP, baPWV was significantly greater than that in Group A and showed a significant correlation with that of hsCRP alone after fluvastatin treatment. In a subgroup of patients (n=26), switching from fluvastatin to rosuvastatin further improved baPWV and the L/H ratio without altering hsCRP after 12 months.. Low-dose rosuvastatin would be more effective than fluvastatin in improving arterial stiffness in high-risk Japanese patients with dyslipidemia. The results suggest that improvement in arterial stiffness by rosuvastatin mainly depends on its strong lipid-lowering effects, whereas that by fluvastatin is strongly dependent on the pleiotropic effects, especially an anti-inflammatory action.

Topics: Aged; Asian People; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluorobenzenes; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Japan; Male; Middle Aged; Prospective Studies; Pyrimidines; Risk Factors; Rosuvastatin Calcium; Sulfonamides; Time Factors; Vascular Stiffness

Anemia, low-grade inflammation and/or alterations in lipid metabolism are common findings in individuals with end-stage renal disease (ESRD) despite advances in dialysis treatment. Hepcidin, a key regulator of iron metabolism, may play an important role in the interdependence of inflammation and anemia in ESRD patients. Statins may reduce cardiovascular events in dialysis patients and have pleiotropic effects in addition to lowering total and low-density lipoprotein (LDL)-cholesterol.. Because there is a paucity of data on the effect of statins on serum prohepcidin levels in dialysis patients, this 8-week study was conducted to test the effect of fluvastatin (80 mg/day, n=22) compared with placebo (n=18) on circulating serum prohepcidin, a prohormone of hepcidin, and high-sensitive C-reactive protein (hs-CRP) in dyslipidemic ESRD patients with renal anemia.. Fluvastatin treatment decreased total cholesterol (P<0.05), LDL-cholesterol (P<0.01), hs-CRP (P<0.05) and serum prohepcidin levels (P<0.05) significantly.. Our pilot data suggest that short-term statin treatment may exert a beneficial effect on serum prohepcidin levels in ESRD patients. The potential clinical benefits of statins on renal anemia need to be confirmed and expanded with an appropriately powered long-term study.

Topics: Adult; Antimicrobial Cationic Peptides; C-Reactive Protein; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hepcidins; Humans; Indoles; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Protein Precursors; Renal Dialysis

Although statin treatment is generally well tolerated, it is estimated that 5% to 10% of patients develop muscle-related side effects (MRSEs), resulting in less effective nonstatin alternatives or cessation of lipid-lowering therapy completely. This study was designed to assess the efficacy and tolerability of extended-release fluvastatin (fluvastatin XL) and ezetimibe alone or in combination in patients with previous MRSEs with other statins. This was a double-blinded, double-dummy trial of 199 mostly moderate- or high-risk dyslipidemic patients randomized to fluvastatin XL 80 mg/day (n = 69), ezetimibe 10 mg/day (n = 66), or fluvastatin XL 80 mg/day plus ezetimibe 10 mg/day (n = 64) for 12 weeks. Fluvastatin XL lowered low-density lipoprotein (LDL) cholesterol by 32.8% compared with 15.6% with ezetimibe (between-group difference -17.1%, 95% confidence interval -23.6 to -10.7, p <0.0001); the fluvastatin XL/ezetimibe combination lowered LDL cholesterol by 46.1% (between-group difference vs ezetimibe -30.4%, 95% confidence interval -37.0 to -23.8, p <0.0001). Proportions of patients achieving their National Cholesterol Education Program Adult Treatment Panel III target LDL cholesterol were 84% with the fluvastatin XL/ezetimibe combination, 59% with fluvastatin XL, and 29% with ezetimibe (p <0.001 for fluvastatin XL monotherapy or combination therapy vs ezetimibe monotherapy). Incidences of MRSEs were 24% in the ezetimibe group, 17% in the fluvastatin XL group, and 14% in the combination group. There were no instances of creatine kinase increases >or=10 times upper limit of normal. In conclusion, in patients with a history of statin-associated MRSEs, fluvastatin XL alone or in combination with ezetimibe offers an effective and well-tolerated lipid-lowering option.

Topics: Anticholesteremic Agents; Azetidines; Cholesterol; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lipoproteins; Male; Middle Aged; Muscular Diseases; Treatment Outcome; Triglycerides

It has been reported that dyslipidaemia impairs left ventricular systolic (LVs) and diastolic (LVd) functions, irrespective of atherogenic effects, in the setting of coronary artery disease. The aim of the present study was to evaluate the effects of anti-lipidaemic therapy on LVs and LVd functions by means of multigated radionuclide ventriculography (RNV) in subjects with signs of dyslipidaemia and with preserved left ventricular function.. Eighteen patients with dyslipidaemia (eight men, 10 women, mean age 50+/-10 years) were included in the study. While the clinical examination and treadmill exercise test results were normal in all patients, low-density lipoprotein levels exceeded 160 mg . dl. Patients with medical conditions including coronary artery disease, hypertension, diabetes, cardiomyopathy and valvular heart disease which would influence left ventricular function were excluded from the study. RNV was performed in all subjects, taking into account the best septal position to differentiate the left ventricle from the right ventricle. The following parameters were calculated: ejection fraction, peak ejection rate (PER), time to peak ejection (TPER), a ejection rate (aER), a ejection fraction (aEF), Peak filling rate (PFR), time to peak filling rate (TPFR), a filling rate (aFR), a filling fraction (aFF).. The low-density lipoprotein value decreased and the high-density lipoprotein value increased after statin therapy (P<0.001 and P<0.003, respectively). PER, aER and aFF significantly increased and TPER decreased as a consequence of statin therapy (respectively, P<0.05, P<0.05, P<0.05 P<0.05).. Anti-lipidaemic therapy is effective in dyslipidaemic patients. RNV is a useful and non-invasive method for monitoring changes in ventricular function following anti-lipidaemic treatment strategies.

Topics: Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gated Blood-Pool Imaging; Humans; Hypolipidemic Agents; Indoles; Longitudinal Studies; Male; Middle Aged; Prognosis; Treatment Outcome; Ventricular Dysfunction, Left

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

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

To elucidate the aggregation capacity of neutrophils in patients with arterial hypertension and dyslipidemia treated with fluvastatin.. 32 middle-aged patients with grade 1-2 AH and dyslipidemia (risk 3). Control group included 26 age-matched healthy subjects. We estimated lipid composition, antioxidant protection, lipid peroxidation in plasma and neutrophils and their aggregation. All patients were given 40 mg fluvastatin at bedtime. Clinical and laboratory characteristics were evaluated before and 4, 16, 52 weeks after treatment. The results were treated by the Student's t-test.. The patients showed enhanced neutrophil aggregation due to lipid imbalance in cell membranes, intense lipid peroxidation, and marked changes in carbohydrate composition of membrane glycoprotein receptors. Fluvastatin significantly improved lipid composition and peroxidation in plasma and neutrophils and caused positive dynamics in their aggregation due to optimization of glycoprotein receptors.

Topics: Cell Aggregation; Dyslipidemias; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Middle Aged; Neutrophils; Treatment Outcome

Dysglycemia and dyslipidemia are important metabolic complications of organ transplantation. Statins are widely used to control dyslipidemia; however, long-term use of statins is related to diabetes mellitus (DM) and impaired fasting glucose (IFG). The aim of this study was to evaluate the influence of statins on the development of dysglycemia (IFG and/or DM) in renal allograft recipients.. A total of 394 patients without previously known DM or IFG who underwent kidney transplantation were enrolled. Patients were grouped into the two groups according to the use of statin (control, n=149; statin, n=245). The major statins used were fluvastatin (80 mg/d, n=134) and atorvastatin (20 mg/d, n=111). We compared the incidence of IFG or DM during the follow-up period.. The incidence of IFG was higher in the statin group than that in the control group (28.6% vs. 8.7%, P<0.001). The incidence of dysglycemia was significantly higher in the statin group (40.0% vs. 15.4%, P=0.001). Time to development of dysglycemia after transplantation was shorter in the statin group than in the control group (38.8±29.7 vs. 47.2±23.3 months, P=0.002). Statin use was associated with an increased risk for dysglycemia after adjustment for age, sex, body mass index, hypertension, cholesterol levels, hepatitis C infection, and type of immunosuppressant (hazard ratio=3.08, 95% confidence interval=1.91-4.98). The dysglycemic effect was more profound in the patients who used atorvastatin than in those who used fluvastatin (hazard ratio=2.21, 95% confidence interval=1.02-4.76).. Statin treatment is associated with an elevation in fasting plasma glucose and in the development of dysglycemia in renal allograft recipients.

Topics: Adult; Anticholesteremic Agents; Atorvastatin; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Dyslipidemias; Fasting; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Glomerular Filtration Rate; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Immunosuppressive Agents; Incidence; Indoles; Kidney Transplantation; Male; Middle Aged; Pyrroles; Renal Insufficiency

Topics: Aged; Brain Ischemia; Consciousness Disorders; Dehydration; Diarrhea; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluid Therapy; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyponatremia; Indoles; Internal Capsule; Natriuresis; Rhabdomyolysis; Sodium Chloride; Thalamus; Vomiting

Lipid-lowering therapy with statins has been associated with decreased mortality and morbidity in heart transplant recipients. Among the available drugs, pravastatin, fluvastatin or low-dose simvastatin have been recommended due to the low risk of pharmacokinetic interaction. However, these first-line statins possess a rather modest lipid-lowering effect and selection of alternative statins is limited due to interactions with cyclosporine (CsA). The aim of this prospective study was to evaluate the safety and efficacy of conversion to tacrolimus and atorvastatin in CsA-treated heart transplant recipients and dyslipidemia refractory to fluvastatin.. Thirty heart transplant recipients taking CsA and fluvastatin 40 to 80 mg/day, with total cholesterol levels of >211 mg/dl, were recruited. After baseline assessment, they were converted to tacrolimus and atorvastatin at a starting dose of 20 mg/day and underwent clinical and laboratory follow-up at 1, 4, 7, 10 and 13 months.. During 13 months of follow-up, treatment with tacrolimus and atorvastatin was tolerated in 24 patients (80%). No case of myotoxicity, liver toxicity or new-onset diabetes was observed. After conversion, the mean cholesterol level (as averaged from levels at 1, 4, 7, 10 and 13 months) was lower than before conversion (183 +/- 24 vs 231 +/- 33 mg/dl, p < 0.0001). When compared with baseline values, conversion also resulted in lower mean LDL-cholesterol levels (92 +/- 25 vs 130 +/- 38 mg/dl, p < 0.0001) and lower mean triglyceride levels (166 +/- 60 vs 220 +/- 101 mg/dl, p < 0.0001).. Conversion to tacrolimus and atorvastatin appears to be a safe and effective lipid-lowering therapy in CsA-treated heart transplant recipients with dyslipidemia refractory to fluvastatin.

Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol; Cohort Studies; Cyclosporine; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Heart Transplantation; Heptanoic Acids; Humans; Immunosuppressive Agents; Indoles; Male; Middle Aged; Prospective Studies; Pyrroles; Tacrolimus; Treatment Outcome; Triglycerides

There is controversy about the effects of statins on insulin resistance and plasma adiponectin. The aim of this study was to investigate the effects of fluvastatin treatment on these parameters in a group of dyslipidaemic patients who had no confounding factors for insulin resistance or alterations in plasma adiponectin.. Forty-nine patients [27 males, 22 females; mean age 47.2 +/- 10.3 years; body mass index (BMI) 29.64 +/- 3.2 kg/m2] with dyslipidaemia and 20 controls (six males, 14 females; mean age 45.3 +/- 9.31 years; BMI 30.07 +/- 4.04 kg/m2) were enrolled. All patients were treated initially with therapeutic lifestyle changes (TLC) for 6 weeks. Six out of 49 subjects were excluded from the study. Then, 24 out of 43 patients with high blood cholesterol despite TLC were allocated to fluvastatin 80 mg daily plus TLC, and the remaining 19 patients with normal cholesterol were subjected to TLC alone for additional 12 weeks.. Plasma adiponectin, immunoreactive insulin levels, BMI, waist circumference, blood pressure, lipids, and glucose were determined. The insulin sensitivity index was quantified using the homeostasis model assessment (HOMA).. TLC caused significant improvement in plasma insulin (P = 0.02) and elevation in plasma adiponectin (P = 0.02). Fluvastatin treatment decreased total cholesterol and low density lipoprotein (LDL)-cholesterol significantly (P = 0.01 and P = 0.02, respectively). No significant effect of fluvastatin was observed on plasma insulin or adiponectin or on the HOMA index.. Fluvastatin does not improve plasma adiponectin levels and insulin sensitivity, despite its beneficial effects on lipid levels. Our data, however, were limited by the fact that a more accurate method of assessing insulin sensitivity, the euglycaemic-hyperinsulinaemic glucose clamp technique, was not used.

Topics: Adiponectin; Adult; Anticholesteremic Agents; Blood Glucose; Case-Control Studies; Cholesterol; Cholesterol, LDL; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Homeostasis; Humans; Indoles; Insulin; Male; Middle Aged; Statistics, Nonparametric; Triglycerides

Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression has been suggested to play an important role in the pathogenesis of atherosclerosis. Lipid-lowering therapy with 3-hydroxy-methylglutaryl-coenzyme A reductase inhibitors reduces the incidence of atherosclerosis-related cardiovascular events. The aim of this study was to establish the effect of a 3-month treatment of fluvastatin on circulating (c)ICAM-1 and standard lipid parameters.. A total of 14 patients (6 men and 8 women), 59.7+/-11 years old, with mean systolic and diastolic blood pressure 135+/-16.3 and 81+/-9.3 mmHg, respectively, fasting plasma cholesterol 6.2+/-1 mmol/L and plasma triglycerides 2.6+/-1 mmol/L, took part in the study. The observed parameters were measured before and after 3 months of therapy.. When comparing total cholesterolemia, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, there were significant decreases after a 3-month treatment. By contrast, no significant difference was observed when we compared the values of triglycerides, high-density lipoprotein (HDL) cholesterol, apolipoprotein A1 and, especially, of cICAM-1. Our results demonstrate the well-known capacity of fluvastatin to lower LDL- and total cholesterol; however, it failed to reduce cICAM after a 3-month treatment.. It can be concluded that a 3-month therapy with fluvastatin does not decrease cICAM-1 levels, despite normalization of cholesterol levels. The implication is that cholesterol may not induce endothelial activation by the initial upregulation of this adhesive molecule.

Topics: Biomarkers; Dyslipidemias; Endothelium, Vascular; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Intercellular Adhesion Molecule-1; Male; Middle Aged

Statins have been shown to significantly reduce morbidity and mortality both in patients with coronary artery disease and in those with dyslipidemia when they are taken regularly. Middle-aged patients have the highest level of forecasting benefit, and little is known about the persistence rate of these therapies in a real-life setting.Objective. To evaluate the persistence rate of middle-aged patients initiating statin therapy as well as its relation to patients' demographic and clinical characteristics.. A cohort of 25,733 patients was reconstructed from prescription data recorded in the Régie de l'assurance maladie du Québec administrative database. All patients aged 50-64 years old who received at least one statin prescription between January 1, 1998 and December 31, 2000 for a new intention of treatment for dyslipidemia were included in the cohort and followed up until June 30, 2001. The date of the first prescription of statin was defined as the index date. The cumulative persistence rate was estimated using a Kaplan-Meier analysis. Cox regression models were used to estimate the rate ratio of ceasing statins after adjustment.. Mean age of patients initiating statin agents was 58 years; 39%were male, 24% received social assistance, 19% had diabetes, 30% had hypertension and 11% had a respiratory disease at cohort entry. Persistence with statin therapy fell to 67% in the first 6 months after treatment and continued to decline over the next 3 years to 39%. At 3 years, persistence varied significantly with statin agents. After controlling for individual patients' demographic and clinical characteristics, we found that patients who were prescribed fluvastatin, lovastatin and atorvastatin had a higher rate of cessation than those on simvastatin and pravastatin. The adjusted rate ratio of ceasing statin agents in patients with other risk factors of cardiovascular disease, such as diabetes (HR: 0.78; 0.75-0.82) or hypertension (HR: 0.72; 0.69-0.74), demonstrated a lower cessation rate. We observed lower persistence in patients who used the greatest number of pharmacies and prescribing physicians.. This analysis indicates that barriers to persistence occur early in the therapeutic course. Overall persistence with statins is low, particularly among patients with few other cardiovascular risk factors.

Topics: Atorvastatin; Cardiovascular Diseases; Drug Prescriptions; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lovastatin; Male; Middle Aged; Patient Compliance; Pyrroles; Regression Analysis; Time Factors

The effects of statins on intima-media thickness (IMT) are well documented, whereas those of fibrates are unknown. Therefore we compared IMT under treatment with each class of drugs.. We studied a cohort of consecutive dyslipidemic subjects treated with statin (n = 291) or fibrate (n = 82) drugs. Fibrate-treated subjects were matched with the same number of statin-treated subjects to obtain two subgroups of similar demographic and risk factors including LDL cholesterol. Common carotid far wall IMT and lumen diameter were measured by ultrasonography.. In the entire study population, IMT was greater in the fibrate group than in the statin group (P < .001), even after adjustment for LDL cholesterol and other covariates (P < .05). In the matched groups, IMT was greater in fibrate group than in the statin group (P < .01), even after adjustment for LDL cholesterol and other covariates including treatment duration (P < .01). The IMT correlated positively with treatment duration in the fibrate group (P < 0.05) but not in the statin group. In addition, IMT correlated positively with carotid lumen diameter in both the fibrate and statin groups (P < .05, P < .01) but with a lower slope in the former (P < .05).. In this study fibrate treatment was associated with greater IMT, steeper IMT-time relationship, and lower compensatory carotid enlargement than was statin treatment. These differences were not explained by differences in LDL cholesterol.

Topics: Adult; Atorvastatin; Bezafibrate; Body Mass Index; Carotid Arteries; Cholesterol, HDL; Clofibric Acid; Cohort Studies; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fenofibrate; Fibric Acids; Fluvastatin; Gemfibrozil; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Male; Middle Aged; Multivariate Analysis; Pravastatin; Pyridines; Pyrroles; Risk Factors; Simvastatin; Treatment Outcome; Tunica Intima; Tunica Media; Ultrasonography