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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Treatment of combined hyperlipidemia with fluvastatin and gemfibrozil, alone or in combination, does not induce muscle damage. 760 87

The accelerated atherosclerosis in diseases associated with elevated remnant lipoprotein levels has directed interest toward the response of this lipoprotein species to lipid-lowering treatment. The effect of fluvastatin--a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor--was compared with that of placebo on parameters of remnant metabolism in 57 patients with moderate hypercholesterolemia, but not heterozygous familial hypercholesterolemia, type III hyperlipidemia, or endogenous hypertriglyceridemia. Fluvastatin therapy resulted in decreases versus baseline in plasma total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL apolipoprotein (apo) B levels of 18%, 20%, and 18%, respectively (p < 0.01). Plasma parameters related to remnant metabolism were also significantly decreased: intermediate density lipoprotein by 43% and apo E by 22% (p < 0.01). The percent decrease in plasma intermediate density lipoprotein cholesterol level was twice that of LDL-C and 50% greater than the decrease seen in very low density lipoprotein cholesterol (VLDL-C), which was decreased by 28%. Total triglycerides were reduced by 11% and VLDL apo B by 24%, whereas high density lipoprotein cholesterol (HDL-C) rose significantly by 8%, HDL2-C by 24%, and HDL3-C by 3%. There were no increases in apo A-I levels compared with placebo nor any significant change in plasma lipoprotein(a) levels. The composition of LDL and VLDL particles did not appear to be altered by therapy, as assessed by the LDL-C:LDL-B, VLDL-C:VLDL-B, or triglyceride:VLDL-B ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of fluvastatin on intermediate density lipoprotein (remnants) and other lipoprotein levels in hypercholesterolemia. 760 88

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.
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PMID:Efficacy and safety of fluvastatin in hyperlipidaemic patients with non-insulin-dependent diabetes mellitus. 798 2

The effects of fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the hyperlipidemia associated with nephrosis were studied. Nephrotic rats, induced by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight), had significantly higher plasma triglyceride (TG), total cholesterol and apoprotein (apo) B concentrations than controls. Fluvastatin was administrated as a 0.01% solution in drinking water for 14 days to either normal control or nephrotic rats. Concentrations of TG and apo B in plasma, and very low-density lipoprotein (VLDL) in nephrosis were completely normalized by the treatment with fluvastatin, but concentrations of cholesterol in plasma and each lipoprotein fraction were not altered by the treatment. The ratio of apo E to C in VLDL was significantly decreased in nephrotic rats, but the fluvastatin treatment increased this ratio. TG secretion rate estimated by the Triton WR1339 method was significantly increased in nephrotic rats, but was normalized by fluvastatin. Percent composition of TG in newly secreted VLDL particles in post-Triton plasma was not decreased by fluvastatin treatment, suggesting that the number of newly secreted VLDL particles was reduced by the treatment. Postheparin plasma lipolytic activities were not affected by the fluvastatin treatment. These results demonstrate that fluvastatin can effectively ameliorate the high concentration of VLDL by suppressing the hepatic secretion in nephrotic rats, and suggest that an inhibition of cholesterol biosynthesis suppresses VLDL secretion from the liver.
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PMID:Fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, suppresses very low-density lipoprotein secretion in puromycin aminonucleoside-nephrotic rats. 807 13

In many patients with primary hyperlipidaemia the statins have become the drugs of choice when diet alone has failed. The usual dosages of statins prescribed in most countries appear to be aimed at producing a reduction in levels of low-density lipoprotein cholesterol (LDL-C) of about 25%. Fluvastatin is the newest member of this class of agent and the first completely synthetic compound. In dose-finding studies, fluvastatin has produced statistically significant (P < 0.001) reductions in LDL-C levels when used in dosages of 20 mg (21%) and 40 mg (27.4%), thus placing it within the range generally expected with usual dosages of other statins; additional studies have shown that the efficacy of fluvastatin is unaffected by gender and age. Moreover, fluvastatin produces the maximum reduction in LDL-C levels within 6 weeks and maintains this efficacy during long-term treatment (LDL-C levels have been reported to fall by 27.4% over 2 years with fluvastatin 40 mg/day). In high-risk patients the LDL-C-lowering effect of fluvastatin 40 mg/day is maintained when compared with low-risk patients (26.6% vs 24.8%). A similar pattern has been observed in hypertensive patients, irrespective of the antihypertensive agent used to control blood pressure. Fluvastatin has been found to produce better LDL-C-lowering effects than bezafibrate. In addition to lowering LDL-C levels by the required amount, 20 and 40 mg (the equivalent of pravastatin 20 mg) dosages of fluvastatin significantly reduce levels of total cholesterol and triglycerides and increase high-density lipoprotein cholesterol levels.
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PMID:Treatment of dyslipidaemias with fluvastatin. 1951 33

Statins are regarded as a well-tolerated class of drugs, particularly when compared with some of the older lipid-modifying agents, which have poor rates of compliance. Despite some early concern, the incidence of lens opacities observed in clinical studies involving statin use is no different from that in a normal ageing population. Similarly, the occurrence of insomnia with lipophilic agents appears to have been overemphasised and is not a clinically significant problem, irrespective of the statin under study. Fluvastatin is the newest representative of this class of agents; it has already been evaluated in thousands of patients who have hyperlipidaemia with and without additional risk factors. In controlled clinical studies, the incidence of the majority of adverse events observed with fluvastatin therapy is no higher than that seen with placebo, with the exception of gastrointestinal disturbances (known to be common to all stains). Nonetheless, the incidence of these effects seen with fluvastatin treatment is noted to be lower than that associated with cholestyramine or fibrate use. Elevations in levels of liver transaminases (aspartate aminotransferase and alanine aminotransferase) have been reported with fluvastatin therapy but have led to discontinuation of treatment with the same frequency as with placebo. Elevations in creatine kinase levels as a cause of discontinuing fluvastatin are not more frequent than with placebo. Drug-related myopathy and rhabdomyolysis have not been reported with fluvastatin therapy, and myalgia does not occur more frequently than with placebo. In terms of drug interactions, fluvastatin does not interfere with the efficacy of antihypertensive agents. In controlled clinical trials, the overall reported discontinuation rate due to adverse events noted with fluvastatin therapy is not significantly distinguishable from the rate associated with placebo.
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PMID:Safety profile of fluvastatin. 1948 70

Occlusive atherosclerosis is a major cause of morbidity and mortality in renal transplant recipients. Hyperlipidemia associated with the transplanted state may be at least partially responsible for this complication and is therefore an important target of therapy. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are powerful cholesterol-lowering drugs, but their broad use in transplant recipients has been hindered by concerns about interactions with cyclosporine. Cyclosporine interferes with the elimination of these agents, increasing their plasma and tissue levels and predisposing the patient to rhabdomyolysis. Fluvastatin, the first entirely synthetic HMG-CoA reductase inhibitor, possesses a distinct pharmacologic profile, including a shorter half-life and virtually no active circulating metabolites. Therefore, it may interact differently with cyclosporine. The pharmacokinetics and safety of fluvastatin, 20 mg/day, were evaluated in 20 hypercholesterolemic renal transplant recipients also receiving cyclosporine, usually in combination with azathioprine and methylprednisolone, during the 14-week study. Fluvastatin area under the curve, maximum plasma concentration, and time to maximum plasma concentration were minimally increased in these patients, unlike findings reported for lovastatin, pravastatin, and simvastatin. This suggests that metabolism of fluvastatin may be less affected by cyclosporine than that of other reductase inhibitors. Fluvastatin was well tolerated, with no evidence of myopathy, rhabdomyolysis, or ophthalmologic abnormalities. These findings and the significant reductions in total cholesterol and low-density lipoprotein cholesterol levels and the ratio of low-density to high-density lipoproteins achieved in these patients support the broader use of fluvastatin to treat hypercholesterolemia in renal transplant recipients.
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PMID:Evaluation of fluvastatin in the treatment of hypercholesterolemia in renal transplant recipients taking cyclosporine. 897 Jun 7

The objective of this study was to compare the lifetime cost-effectiveness of HMG-CoA reductase inhibitors and fibrates for the treatment of hyperlipidemia. Estimates of lipid modification achieved due to drug therapy were based on published head-to-head comparisons of specific HMG-CoA reductase inhibitors and fibrates in randomized, double-blind studies. We used a validated coronary heart disease (CHD) prevention computer model to estimate the costs and benefits of lifelong lipid modification. The patients were middle-aged men and women who were free of CHD, with either primary type IIa or IIb hyperlipidemia. The intervention used were specific HMG-CoA reductase inhibitors and fibrates at several dosages, which reduced total cholesterol 11-34% and increased high-density lipoprotein cholesterol 1-29%. The main outcome measure was the cost per year of life saved after discounting benefits and costs by 5% annually. The lifetime cost effectiveness of HMG-CoA reductase inhibitors (fluvastatin, lovastatin, pravastatin, simvastatin) and fibrates (bezafibrate, fenofibrate, gemfibrozil) for the treatment of primary hyperlipidemia varied according to patient population, the effectiveness of each drug in modifying lipid levels, and the price of each drug. The estimates of cost per year of life saved for HMG-CoA reductase inhibitors range from $19,886 to $73,632, and $16,955 to $59,488 for fibrates according to gender and type of primary hyperlipidemia. Fluvastatin 20 mg/day was significantly more cost effective than gemfibrozil 1200 mg/day for male patients with type IIa hyperlipidemia. Simvastatin 17.3 mg/day or 20 mg/day yielded similar cost-effectiveness ratios compared with fibrates among type II hyperlipidemic patients. However, micronized fenofibrate was more cost effective than simvastatin 20 mg/day among type IIb patients. The cost effectiveness of lipid therapy varies widely and can be maximized by selecting specific drugs for specific lipid abnormalities.
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PMID:A head-to-head comparison of the cost effectiveness of HMG-CoA reductase inhibitors and fibrates in different types of primary hyperlipidemia. 911 Jan 23

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.
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PMID:Fluvastatin (Lescol) treatment of hyperlipidaemia in patients with renal transplants. 920 45

Preliminary data suggest that fluvastatin may be safely combined with fibrates. The Fluvastatin Alone and in Combination Treatment Study examined the effects on plasma lipids and safety of a combination of fluvastatin and bezafibrate in patients with coronary artery disease and mixed hyperlipidaemia. A total of 333 patients were randomly allocated in this multicentre double-blind trial to receive 40 mg fluvastatin alone (n=80), 400 mg bezafibrate (n=86), 20 mg fluvastatin+400 mg bezafibrate (n=85) or 40 mg fluvastatin+400 mg bezafibrate (n=82) for 24 weeks. Low-density lipoprotein (LDL)-cholesterol decreased >20% in all fluvastatin-containing regimens, with significantly greater decreases compared with bezafibrate alone (P<0.001). Bezafibrate alone and fluvastatin+bezafibrate combinations resulted in greater increases in high-density lipoprotein (HDL)-cholesterol and decreases in triglycerides compared with fluvastatin alone (P<0.001). Fluvastatin (40 mg)+bezafibrate was the most effective for all lipid parameters with a decrease from baseline at endpoint in LDL-cholesterol of 24%, a decrease in triglycerides of 38% and an increase in HDL-cholesterol of 22%. All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy, or between combination regimens. No clinically relevant liver (aspartate aminotransferase [ASAT] or alanine aminotransferase [ALAT]) greater than three times the upper limit of normal) or muscular (creatine phosphokinase (CPK) greater than four times the upper limit of normal) laboratory abnormalities were reported. This large study shows 40 mg fluvastatin in combination with 400 mg bezafibrate to be highly effective and superior to either drug given as monotherapy in mixed hyperlipidaemia, and to be safe and well tolerated.
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PMID:Efficacy and safety of a combination of fluvastatin and bezafibrate in patients with mixed hyperlipidaemia (FACT study). 1129 92


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