Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of recently published studies on primary and secondary prevention of coronary heart disease with HMG-CoA reductase inhibitors--statins--support their use in patients with primary hypercholesterolaemia or mixed hyperlipidaemia, with or without atherosclerotic vascular disease. From a pharmacological point of view, statins inhibit HMG-CoA reductase, reduce the endogenous synthesis of cholesterol and increase the apoB/apoE lipoprotein clearance from plasma. Recent studies confirm that HMG-CoA reductase inhibitors may also decrease hepatic production of VLDL and LDL-cholesterol. However, they have different pharmacokinetic properties and variable effectiveness with potential clinical implications. These drugs are generally well tolerated with a similar profile of adverse effects (gastrointestinal effects, hepatic dysfunction and myopathy). The knowledge of their pharmacodynamic and pharmacokinetic properties can lead to a rational use and greater understanding of their potential benefits.
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PMID:[HMG-CoA reductase inhibitors: a brief review of their pharmacological properties and clinical efficacy in cardiovascular disease]. 1009 28

HMG-CoA reductase inhibitors reduce serum total cholesterol concentrations and the risk of coronary heart disease in patients with hypercholesterolemia. Recently, it has been reported that patients with combined hyperlipidemia are also at risk of coronary heart disease. However, HMG-CoA reductase inhibitor therapy alone does not sufficiently reduce serum triglyceride concentrations. Epidemiological and clinical evidence has shown that fish oil can lower plasma lipid levels, especially triglycerides. Consequently, we investigated the effects of the combination of HMG-CoA reductase inhibitors and eicosapentaenoic acid, a major component of fish oil, on hyperlipidemia. We administered 900-1,800 mg/day of the ethyl ester of eicosapentaenoic acid to patients with hyperlipidemia who had been treated with HMG-CoA reductase inhibitors for 30 +/- 6 months (means +/- SE). Serum total cholesterol and triglyceride concentrations were significantly decreased 3 months after the administration of eicosapentaenoic acid (from 5.63 +/- 0.23 mmol/l to 5.02 +/- 0.20 mmol/l, P < 0.05; from 2.07 +/- 0.41 mmol/l to 1.08 +/- 0.17 mmol/l, P < 0.01, respectively). Serum high-density lipoprotein-cholesterol concentrations were significantly increased after the treatment (from 1.23 +/- 0.12 mmol/l to 1.34 +/- 0.13 mmol/l, P < 0.05). Plasma eicosapentaenoic acid concentrations and the ratio to arachidonic acid in plasma were also significantly increased 3 months after the treatment (from 101.9 +/- 8.1 mg/l to 181.8 +/- 23.9 mg/l, P < 0.001; from 0.640 +/- 0.075 to 1.211 +/- 0.170, P < 0.001, respectively). These results suggested that the combination therapy of HMG-CoA reductase inhibitors and eicosapentaenoic acid was effective for patients with hyperlipidemia.
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PMID:Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. 1035 59

Xuezhikang is a new blood-lipid-regulating medicine. The components of Xuezhikang include HMG-CoA reductase inhibitor (lovastatin), unsaturated fatty acids and many kinds of amino acids. A comparative study on the effects of Xuezhikang and Simvastatin (Zocor) was carried out. One hundred and eight patients with primary hyperlipidemia were randomly divided into two groups. Group 1 consisted of 53 patients, each taking 4 Xuezhikang capsules/day (1.2 g/day) for 8 weeks and group 2 included 55 cases, each taking Zocor 10 mg/day for 8 weeks. At the end of 8 weeks, the lipid levels were compared with those of the baseline in each group. In group 1 serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were decreased by 23.0%, 28.0% and 28.1% (P < 0.001) respectively and in group 2 they were reduced by 23.3%, 29.5% and 29.5% (P < 0.001) respectively. Serum level of high density lipoprotein (HDL-C) was increased by 5.0% (P > 0.05) with Xuezhikang and 14.3% (P < 0.01) with Zocor, but no significant differences were found between the two groups in TC, LDL-C, TG and HDL-C. The side effects of Xuezhikang were less than those of Zocor. It is suggested that Xuezhikang made in China is a safe, effective and tolerable lipid modulator.
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PMID:[Effect of xuezhikang on the treatment of primary hyperlipidemia]. 1043 58

BACKGROUND: Atorvastatin, a new HMG-CoA reductase inhibitor in clinical development has demonstrated an acceptable safety profile and marked cholesterol and triglyceride reduction at doses ranging from 10-80 mg/day. Since bile acid sequestering resins are often used in combination with HMGRIs to enhance cholesterol reduction, this trial was conducted to explore the use of atorvastatin alone and combined with colestipol in patients with primary hyperlipidemia. METHODS AND RESULTS: One hundred six patients with low-density lipoprotein (LDL) cholesterol >4.1 mM/L (160 mg/dL) and plasma triglycerides <3.9 mM/L (350 mg/dL) were randomized to treatment consisting of 20 g/day colestipol, 10 mg/day atorvastatin, or 10 mg/day atorvastatin plus 20 g/day colestipol for 12 weeks. Percent change from baseline in lipid variables were measured. The atorvastatin group showed a significant reduction in LDL cholesterol of 35% after 12 weeks. Combination therapy provided an additional 10% reduction in LDL cholesterol over that observed for atorvastatin alone. Twenty-one percent of all patients in the atorvastatin monotherapy group experienced associated adverse events compared with 60% in the combination therapy group. Ninety percent of atorvastatin monotherapy patients were compliant at every visit compared with 75% receiving combination therapy. CONCLUSIONS: Although the combination of atorvastatin plus colestipol was more effective in lowering LDL cholesterol than atorvastatin alone, atorvastatin 10 mg/day monotherapy provided a better safety profile and improved patient compliance, which may result in improved long-term cholesterol control.
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PMID:Atorvastatin, a New HMG-CoA Reductase Inhibitor as Monotherapy and Combined With Colestipol. 1068 8

BACKGROUND: Pravastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase. It prevents mevalonate synthesis, reducing endogenous cholesterol production, and reduces cholesterol content in the liver, thus resulting in a down-regulation of low-density lipoprotein receptor production. Gemfibrozil reduces very low-density lipoprotein production and low-density lipoprotein-cholesterol level and increases very low-density lipoprotein catabolism. Therefore, it was suggested that combination therapy with both drugs could effect greater reduction of cholesterol levels as compared to pravastatin alone. The present study was carried out to evaluate the efficacy and safety of pravastatin as a monotherapy or in combination with gemfibrozil in the treatment of patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia. METHODS AND RESULTS: Forty-one patients were included in the study. All patients initially followed 6 weeks of hypolipidemic diet; subsequently they were randomized and received either 20 mg once daily of pravastatin alone (n = 13) or 20 mg of pravastatin together with 600 mg of gemfibrozil twice daily (n = 14). As a control, 14 patients were treated with diet only. The treatment lasted 24 months and clinical evaluation and laboratory tests were done at given time points. Both groups of treated patients showed an early reduction (3 months) of total (about 30% P <.01 vs controls), low-density lipoprotein (about 35%, P <.01 vs controls) and very low-density lipoprotein cholesterol levels (about 18%, P = NS). In contrast, high-density lipoprotein cholesterol levels increased significantly in patients treated with pravastatin and gemfibrozil (about 20%, P <.05 vs controls). Pravastatin treatment alone reduced the level of serum triglycerides as efficiently as in combination with gemfibrozil. Data showed a sustained normalization of lipid profile until 24 months. However, this effect was achieved in patients that had rather low levels of triglycerides. During the treatment we did not observe any difference in the incidence of possible drug-related side effects. Severe myopathy or rhabdomyolysis was not observed at the doses of the drugs used in our study. CONCLUSIONS: Therapy with pravastatin and in combination with gemfibrozil resulted in significant and sustained normalization of lipid profile in high-risk patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia.
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PMID:Long-term Treatment With Pravastatin Alone and in Combination With Gemfibrozil in Familial Type IIB Hyperlipoproteinemia or Combined Hyperlipidemia. 1068 38

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.
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PMID:Efficacy and tolerability of fluvastatin and bezafibrate in patients with hyperlipidemia and persistently high triglyceride levels. 1071 Jan 19

Cerivastatin, commercialized under the trade names of Lipobay by Bayer and Cholstat by Fournier Pharma, is a new synthetic statin. Because of its high affinity for HMG-CoA reductase enzyme that it specifically and selectively inhibited in the hepatocytes, cerivastatin exerts its cholesterol-lowering effect at very low doses, between 0.1 and 0.3 mg/day. Cerivastatin is indicated, after diet failure, in the treatment of primary forms of isolated hypercholesterolaemia or combined hyperlipidaemia. It is presented by the two pharmaceutical companies as 0.1, 0.2 and 0.3 mg filmed tablets. Usual dose is 0.3 mg, once daily, to be reduced in presence of renal failure. Cerivastatin is metabolised within the liver by two different families of cytochrome P450, which limits the risk of drug interferences. Besides this potential advantage as compared with some other statins, its pharmacodynamic activity and safety profile seem to be similar to those of other agents of the same pharmacological family.
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PMID:[Pharmacy clinics. Medication of the month. Cerivastatin (Lipobay, Cholstat)]. 1076 83

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol) is a new hypocholesterolemic drug effectively reducing total cholesterol, LDL cholesterol, and apolipoprotein (apo) B in experimental animals and in humans. In contrast to fibrates and HMG-CoA reductase inhibitors the cholesterol and triglyceride lowering effect of Lifibrol is not accompanied by increases in HDL cholesterol and apoA-I levels. We examined the impact of Lifibrol on the metabolism of HDL apoA-I in patients with hyperlipoproteinemia, using endogenous labeling with stable isotopes. Kinetic studies were performed in five male hypercholesterolemic individuals (type IIa), before and on treatment with 450 mg of Lifibrol daily for 4 weeks and in five male individuals suffering from mixed hyperlipidemia (type IIb), before and on therapy, for 12 weeks. Lifibrol reduced total cholesterol by 14% (P=0.02) and LDL cholesterol by 16% (P=0. 014) in all patients, and decreased triglycerides by 34% in type IIb patients. During Lifibrol therapy, HDL cholesterol and ApoA-I concentrations did not change. Tracer kinetics revealed that the fractional catabolic rate (FCR) of HDL apoA-I increased by 22% (P=0. 013). This increase in the apoA-I FCR was accompanied by a 23% increase in HDL apoA-I production rate (P=0.006). We conclude that Lifibrol, although not changing HDL steady state concentrations, enhances the turnover of apoA-I containing HDL particles.
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PMID:HDL steady state levels are not affected, but HDL apoA-I turnover is enhanced by Lifibrol in patients with hypercholesterolemia and mixed hyperlipidemia. 1078 41

HMG-CoA reductase inhibitors (lovastatin, simvastatin, fluvastatin, pravastatin) constitute a potent class of cholesterol-lowering agents, which are increasingly being used these days for primary and secondary prevention of atherosclerotic heart disease. Despite having good overall safety and efficacy profiles, these medications can still cause significant adverse effects including transient elevation of hepatic transaminases, myopathy, and rhabdomyolysis. Preclinical studies have demonstrated a potential of neoplasia in rats. However in clinical trials HMG-CoA reductase inhibitors have not been found to be neoplastic in humans. The dosage used in humans is also significantly lower and therefore it is expected to have a good safety margin. But this may not be entirely true considering the mechanism of neoplastic transformation, which is thought to be different in humans as compared to other species. We report a patient, who developed follicular adenoma with prominent Hurthle cell changes after being on simvastatin for three months but not during one year of pravastatin therapy. In elderly female patients with hyperlipidemia requiring pharmacologic treatment, especially those with a prior history of multinodular goiter, one should consider using an agent which has not been shown to cause thyroid tumors even in animal models. Patients should continue to be followed with frequent periodic thyroid palpation in addition to the usual biochemical monitoring required while on these agents.
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PMID:Development of thyroid follicular adenoma on simvastatin therapy. 1084 48

Despite the availability of various lipid lowering drugs, the treatment of hyperlipidemia, one of the most important risk factors for morbidity and mortality after organ transplantation, remains a therapeutic challenge. We investigated the safety and efficacy of a new HMG-CoA reductase inhibitor, atorvastatin, in renal transplant patients whose serum lipids were insufficiently controlled by diet and treatment with other lipid lowering drugs. Twenty-four patients (14 males/10 females; mean age 51.2 +/- 2.3 years) were converted to low dose atorvastatin (10 mg/day) at a mean of 67.7 +/- 8.6 months after renal transplantation and prospectively followed for 3 months after initiation of the study drug. HDL, LDL, and total cholesterol, triglycerides, serum creatinine and CPK levels were evaluated pre (-3, -1, 0 months) and post conversion (+1, +3 months). In the eighteen patients who completed the study, low dose atorvastatin therapy led to a significant reduction in total cholesterol (304.6 +/- 13.2 vs. 247.6 +/- 12.0 mg/dl; p = 0.007) and LDL cholesterol (191.9 +/- 9.0 vs. 141.8 +/- 14.7 mg/dl; p < 0.0001) and a modest reduction in serum triglyceride levels at three months after conversion. We conclude that low dose atorvastatin (10 mg/day) can be successfully used and appears to be safe in the treatment of posttransplant hyperlipidemia. Its long-term effects on patient morbidity and mortality as well as graft survival should be investigated in larger and more prolonged prospective trials.
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PMID:Beneficial effects of atorvastatin in the treatment of hyperlipidemia after renal transplantation. 1084 41


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