Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0231528 (myalgia)
 6,565 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin-fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin-fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side-effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.
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PMID:High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia. 966 52

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, interactions, and formulary considerations of atorvastatin relative to other hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are discussed. Atorvastatin calcium, a synthetic stereoisomer of a pentasubstituted pyrrole, prevents the conversion of HMG-CoA by competitive and selective inhibition of HMG-CoA reductase. This limits cholesterol formation. Atorvastatin undergoes extensive first-pass metabolism; the first-pass effect is saturable at higher doses. Time to maximum plasma concentration ranges from one to four hours. The plasma elimination half-life is considerably longer than for other statins. Like other statins, atorvastatin reduces low-density-lipoprotein cholesterol (LDL-C) and total cholesterol in patients with hypercholesterolemia. However, the reductions achieved with atorvastatin exceed those for other statins. Atorvastatin recipients are more likely to achieve LDL-C goals and to do so more quickly. Atorvastatin also moderately reduces triglyceride levels in patients with hypertriglyceridemia and may play a role in the management of familial hypercholesterolemia. Adequate lipid control with atorvastatin monotherapy may preclude the need for combination drug therapy in some patients. The adverse effects of atorvastatin include mild gastrointestinal disturbances, increased liver enzyme levels, and myalgia. Drug interactions involving atorvastatin can be expected to parallel those of other statins metabolized via CYP3A4. Atorvastatin has become a popular addition to hospital formularies, even though formal pharmacoeconomic analyses are lacking. Atorvastatin effectively reduces blood lipids and may offer some advantages over other statins, but more studies are needed to clarify its optimal role in pharmacotherapy.
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PMID:Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor. 1055 20

This study compared the efficacy of simvastatin 80 mg and atorvastatin 80 mg in the treatment of 26 patients with familial hypercholesterolaemia over 12 weeks using an open crossover trial format. Both, similarly, reduced LDL by 47 +/- 13% and 43 +/- 16% and median triglycerides by 22% and 27% respectively. However, atorvastatin reduced HDL by 2 +/- 24% compared with 8 +/- 30% increase with simvastatin (p = 0.05) affecting the LDL:HDL ratio achieved (4.478 +/- 1.56 vs 3.74 +/- 0.93, p = 0.001). Atorvastatin raised median fibrinogen by 15% compared with a non-significant 5% increase with simvastatin (p = 0.05). Simvastatin reduced lipoprotein (a) by a median 20% compared with baseline (p = 0.05) compared with 5% for atorvastatin. Side-effects, mostly gastrointestinal, were seen in four patients (16%) with atorvastatin compared with one case of myalgia with simvastatin (4%). We conclude both drugs are equally effective in LDL reduction but that simvastatin is superior in raising HDL and causes fewer side-effects. These results require confirmation in larger studies.
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PMID:Comparison of therapy with simvastatin 80 mg and atorvastatin 80 mg in patients with familial hypercholesterolaemia. 1069 48

Elevated levels of serum lipids and lipoproteins are known to play a major role in the development of atherosclerosis and subsequent coronary heart disease (CHD). In controlled clinical studies, atorvastatin (Sortis), a new 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA)-reductase inhibitor, proved to be a very effective and safe lipid-lowering agent. The aim of this open-label, multicentre study (without a control group) was to confirm the efficacy and safety of atorvastatin in a private practice group, including 181 Swiss cardiologists, internists, and general practitioners. A total of 877 hyperlipidaemic patients requiring treatment participated in this study. To evaluate the effectiveness of the treatment with atorvastatin over a period of 12 weeks, total plasma cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides (TG) were determined every 4 weeks. The initial atorvastatin dose was 10 mg in 78% of patients and 20 mg in 22%. The dose was doubled every 4 weeks until the target values of TC < or = 5.2 mmol/l and TC/HDL < or = 5 were reached. After 12 weeks of treatment with atorvastatin the mean reduction in TC, TC/HDL, LDL and TG compared to baseline levels was 33, 37, 42, and 25% respectively. At the same time the HDL concentration was increased by 9%. These results were evidenced in patients with existing coronary heart disease, in high risk patients without manifest coronary heart disease and in patients with significantly elevated lipid levels (TC > 7.8 mmol/l, TC/HDL > 6.5). After treatment with atorvastatin for 12 weeks, 59% of patients had reached the therapeutic target of TC < or = 5.2 mmol/l. The target of TC/HDL < or = 5 was reached by 79%. Atorvastatin was almost without exception well tolerated, the most frequently reported side effects being nausea, myalgia, and headache. In this open-label multicentre study atorvastatin was found to be effective and well tolerated. The observed reduction in the lipid and lipoprotein concentration is in accordance with the results of published controlled studies. The lipid and lipoprotein concentrations were decreased significantly in patients with slight to moderate elevation of lipid levels as well as in those with significantly raised values.
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PMID:[Evaluating the efficacy and tolerance of atorvastatin in hyperlipidemia in general practice (SWITCH Study)]. 1089 90

Lowering of serum cholesterol levels by pharmacologic intervention with statins reduces the incidence of cardiovascular events in subjects with and without atherosclerotic manifestations. In an 8-week, randomized, double-blind study we compared the efficacy and safety of the new compound atorvastatin for reducing LDL-cholesterol (LDL-C) with placebo in an Asian patient cohort. Patients with LDL-C between 160 mg/dl and 250 mg/dl were randomly assigned to treatment with 10 mg atorvastatin or placebo once daily for 8 weeks. At the end of weeks 4 and 8 of the randomized phase, the serum concentrations of lipid parameters as well as safety parameters were determined. Fifty-four patients (32 males and 22 females) were enrolled. Twenty-six patients were assigned to the treatment group. The primary end-point, LDL-C, was reduced by 40% and 42% after 4 and 8 weeks of treatment in the atorvastatin treated patients (p<0.001). The reductions in total cholesterol and triglycerides were up to 31% and 23%, respectively. The HDL-C levels increased up to 11% (p=0.043). There were no significant adverse events. Transient increases in CPK levels (10 times) without myalgia were identified in 1 patient. Atorvastatin, 10 mg/day produced significant reductions in LDL-C, total cholesterol and triglycerides and an elevation of HDL-C levels when used as an adjunct to diet in hyperlipidemic patients. The majority of the clinical effects could be attained by week 4. The overall safety profile of atorvastatin was similar to that of placebo. Atorvastatin was considered to be well tolerated in this patient cohort.
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PMID:A randomized, double-blind, placebo-controlled, 8-week study to evaluate the efficacy and safety of once daily atorvastatin (10 mg) in patients with elevated LDL-cholesterol. 1193 22

Atorvastatin is metabolized through enzymes encoded by members of the cytochrome P-450 (CYP) 3A gene family. Some patients who take atorvastatin along with concomitant medications known to inhibit CYP3A enzyme activity (e.g. itraconazole) develop rhabdomyolysis secondary to a severe drug-induced myopathy. The present study aimed to characterize the relationship between CYP3A gene polymorphisms and atorvastatin-induced muscle damage in the context of concomitant medication. The study employed a retrospective case--control (n=137) design. Study subjects were recruited from the general patient population served by Marshfield Clinic, a large horizontally integrated multispecialty group practice located in central Wisconsin, and case assignment was based upon both subjective (myalgia) and objective inclusion criteria [elevated serum creatine kinase (CK) levels]. The primary outcome was the relationship between serum CK level and CYP3A genotype. CYP3A genotype was not associated with an increased risk for the development of atorvastatin-induced muscle damage. CYP3A4*1B and CYP3A5*3 allele frequencies were similar in cases (n=68) and controls (n=69). Conversely, CYP3A genotype was associated with an increased severity of atorvastatin-induced muscle damage. An association was identified between the non-functional CYP3A5*3 allele and the magnitude of serum CK elevation in case patients experiencing myalgia. Patients who were homozygous for CYP3A5*3 demonstrated greater serum CK levels than patients who were heterozygous for CYP3A5*3, when concomitant lipid-lowering agents were sequentially removed from the analysis (P=0.025 without gemfibrozil, P=0.010 without gemfibrozil and niacin). The study demonstrates that patients who develop myalgia while taking atorvastatin are more likely to experience a greater degree of muscle damage if they express two copies of CYP3A5*3.
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PMID:Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage. 1590 Feb 15

Atorvastatin has been shown to reduce coronary events and revascularization procedures in patients with multiple risk factors for coronary heart disease. Recent studies with atorvastatin 80 mg support the overall safety of this dose during long-term treatment. However, physicians appear reluctant to use high doses of statins. A retrospective analysis of pooled data from 49 clinical trials of atorvastatin in 14,236 patients treated for an average period of 2 weeks to 52 months was conducted. The study compared the safety of atorvastatin 10 mg (n = 7,258), atorvastatin 80 mg (n = 4,798), and placebo (n = 2,180) and included analyses on treatment-associated adverse events; nonserious and serious adverse events related to the musculoskeletal, hepatic, and renal systems; the incidence of elevations of creatine kinase >10 times the upper limit of normal (ULN); and hepatic transaminases >3 times ULN. Percentages of patients experiencing > or =1 adverse event were similar across all 3 groups. Withdrawals due to treatment-related adverse events were observed in 2.4%, 1.8%, and 1.2% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. Serious adverse events were rare and seldom led to treatment withdrawal with any dose. Treatment-associated myalgia was observed in 1.4%, 1.5%, and 0.7% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. No cases of rhabdomyolysis were reported in any group. Persistent elevations in hepatic transaminases >3 times ULN were observed in 0.1%, 0.6%, and 0.2% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. The incidence of treatment-associated adverse events for atorvastatin 80 mg was similar to that of atorvastatin 10 mg and placebo. In conclusion, the results of this analysis support the positive safety profile of atorvastatin at the highest dose.
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PMID:Comparative safety of atorvastatin 80 mg versus 10 mg derived from analysis of 49 completed trials in 14,236 patients. 1675 8

The lipid-lowering and anti-atherosclerotic effects of atorvastatin (10 mg/day) were investigated by measuring changes in the levels of oxidized low-density lipoprotein (LDL), serum lipids (total cholesterol [TC], LDL-cholesterol [LDL-C] and triglycerides [TG]), and in the protein adiponectin. This was undertaken in 22 patients with ischaemic heart disease and serum LDL-C levels > 100 mg/dl. After 3 months of therapy, atorvastatin significantly decreased serum lipids, oxidized LDL was reduced from 457.0 +/- 148.6 to 286.9 +/- 88.5 nmol/l, and adiponectin increased from 9.7 +/- 7.4 to 13.9 +/- 9.98 microg/ml. No significant correlation was observed between adiponectin and LDL-C, TG and high-density lipoprotein cholesterol. Atorvastatin therapy was not associated with side-effects, such as myalgia and gastrointestinal disorders, and did not give abnormal laboratory test results. It is concluded that atorvastatin decreases serum lipid and oxidized LDL levels, and increases adiponectin levels in patients with ischaemic heart disease.
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PMID:Efficacy of atorvastatin therapy in ischaemic heart disease - effects on oxidized low-density lipoprotein and adiponectin. 1769 31

The objective of this study was to evaluate the safety and tolerability of atorvastatin 10 mg compared with placebo in 2,838 patients with type 2 diabetes and no history of coronary heart disease who were enrolled in the Collaborative Atorvastatin Diabetes Study (CARDS) and followed for 3.9 years. The percentages of patients experiencing treatment-associated adverse events (AEs), serious AEs and discontinuations due to AEs in the atorvastatin (n=1,428) and placebo (n=1,410) groups were 23.0% vs. 25.4%, 1.1% vs. 1.1% and 2.9% vs. 3.4%, respectively. The most common treatment-associated AEs in the atorvastatin and placebo groups were digestive system-related (8.9% vs. 10.0%). All-cause and treatment-associated myalgia were reported in 4.0% and 1.0% of atorvastatin-treated patients, and 4.8% and 1.2% of placebo-treated patients. An analysis of selected AEs by tertiles of baseline low-density lipoprotein (LDL) cholesterol showed no relationship between LDL cholesterol levels and the incidence of myalgia, cancer or nervous system AEs in either treatment group. Overall, these data demonstrate that atorvastatin 10 mg was well tolerated in patients with type 2 diabetes during long-term treatment.
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PMID:The safety and tolerability of atorvastatin 10 mg in the Collaborative Atorvastatin Diabetes Study (CARDS). 1877 90

We report the case of a patient who exhibited severe acute hepatitis with symptomatic cholestasis for more than 3 months and bile duct injury following the prescription of atorvastatin. After withdrawal the drug, the patient's wellbeing slowly improves and biological features normalize in 4 months. Therapy aimed at treating severe liver steatosis and hypercholesterolemia. Atorvastatin is a highly effective 3-hydroxy-3 methylglutamyl- coenzyme A reductase (statin) used to lower low-density lipoprotein. Reported frequent adverse events of the medication include nausea, depression, myalgia, abdominal pain and abnormal liver function tests. Although abnormal liver function tests is not an uncommon side effect of the medication, more serious liver injury is rare. In a recent literature review, about ten cases of serious hepatotoxicity have been documented. In the typical presentation, the duration of exposure prior to hepatic toxicity is variable. Liver injury is generally of the mixed type. A prolonged cholestasis for more than 3 months has been seldom reported. Morphological changes includes canalicular cholestasis, feathery degeneration but no cholangiolitis nor cholangitis under the form of cytological and inflammatory changes at the level of interlobular bile ducts. This case report provides further evidence that among statins, atorvastatin may be implicated in drug-induced liver injury and indicates for the first time that such liver injury may be followed by prolonged cholestasis and interlobular bile duct injury. Atorvastatin has thus to be added to the list of medication potentially responsible for bile duct injury.
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PMID:Severe acute cholestatic hepatitis with prolonged cholestasis and bile-duct injury following atorvastatin therapy: a case report. 1919 78


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