Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the major side-effects of the use of HMG CoA reductase inhibitors for the treatment of hypercholesterolemia is the development of myositis and, in some patients undergoing concomitant immunosuppressive treatment, the development of rhabdomyolysis. Experiments outlined in these studies demonstrate that inhibitors of HMG-CoA reductase activity which differ primary in the substitution of a methyl group for a hydroxyl group have differential effects on both cholesterol levels and cell viability in a striated muscle cell model, the mouse C2-C12 myoblast. Thus, concentrations as high as 200 microM of pravastatin had little effect on total cholesterol level while 25 microM of lovastatin decreased cellular cholesterol by over 90%. Simvastatin and lovastatin decreased viability of C2-C12 myoblasts by nearly 50% at concentrations as low as 1 and 5 microM, respectively, and decreased viability by almost 90% at 10 and 15 microM respectively. However, 300 microM of pravastatin decreased cell viability by less than 50%. The order of potency for the effects on cell viability wassimvastatin>lovastatin>>>pravastatin. The possible relationship between effects on cell viability and the development of myositis is discussed.
J Mol Cell Cardiol 1995 Oct
PMID:Differential sensitivity of C2-C12 striated muscle cells to lovastatin and pravastatin. 857 54

The findings in this case indicate that atorvastatin, like other DL-3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, may increase the risk of myositis and rhabdomyolysis when used in combination with gemfibrozil.
Am J Cardiol 1998 Feb 01
PMID:Rhabdomyolysis after taking atorvastatin with gemfibrozil. 946 88

The objective of this multicenter, randomized, open-label, parallel-group, 8-week study was to evaluate the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin 10, 20, 40, and 80 mg compared with simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20, 40, and 80 mg, and fluvastatin 20 and 40 mg. Investigators enrolled 534 hypercholesterolemic patients (low-density lipoprotein [LDL] cholesterol > or = 160 mg/dl [4.2 mmol/L] and triglycerides < or = 400 mg/dl [4.5 mmol/L]). The efficacy end points were mean percent change in plasma LDL cholesterol (primary), total cholesterol, triglycerides, and high-density lipoprotein cholesterol concentrations from baseline to the end of treatment (week 8). Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in LDL cholesterol, -38%, -46%, and -51%, respectively, than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. Atorvastatin 10 mg produced LDL cholesterol reductions comparable to or greater than (p < or = 0.02) simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20 and 40 mg, and fluvastatin 20 and 40 mg. Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in total cholesterol than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. All reductase inhibitors studied had similar tolerability. There were no incidences of persistent elevations in serum transaminases or myositis.
Am J Cardiol 1998 Mar 01
PMID:Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) 1132 75

To evaluate the effects of the addition of pimobendan to an optimal basic regimen on plasma levels of neurohumoral factors in patients with non-ischemic, moderate heart failure during 2-year follow-up. This prospective, observational study involved 16 patients with non-ischemic, moderate heart failure [New York Heart Association (NYHA) functional class IIM-III] receiving an optimal basic regimen of digitalis, diuretics and angiotensin-converting enzyme inhibitor. Eight patients (Group P) were also administered pimobendan at a dose of 2.5 or 5 mg daily, while the other 8 served as controls (Group C). After 3 months of pimobendan administration, the plasma levels of norepinephrine and atrial natriuretic peptide and brain natriuretic peptide decreased and left ventricular ejection fraction improved. After 1 year, the cardiac symptoms, assessed using the Specific Activity Scale as well as the NYHA functional class, improved and the left ventricular end-diastolic diameter decreased. These improvements in Group P were maintained for 2 years. However, in Group C, the cardiac symptoms and the neurohumoral factor levels remained unchanged or deteriorated during this study, and one patient died of heart failure. Long-term combination therapy with the optimal basic regimen and pimobendan has potentially beneficial effects on neurohumoral factor levels and cardiac symptoms in patients with non-ischemic, chronic moderate heart failure.
J Cardiol 1999 Jun
PMID:Effects of long-term treatment with pimobendan on neurohumoral factors in patients with non-ischemic chronic moderate heart failure. 1039 5

Older men and women with coronary artery disease, prior stroke, peripheral arterial disease, and extracranial carotid arterial disease with a serum low-density lipoprotein (LDL) cholesterol > 125 mg/dL despite diet should be treated with lipid-lowering drug therapy, preferably with statins, to reduce the serum LDL cholesterol to < 100 mg/dL. If statin drug therapy does not lower the serum LDL cholesterol to < 100 mg/dL in older persons with coronary artery disease, a bile acid binding resin, such as cholestyramine, should be added, since this drug does not increase the incidence of myositis in persons taking statins. The physician should use statins to treat older persons without atherosclerotic cardiovascular disease with a serum LDL cholesterol > or = 160 mg/dL plus one major risk factor, or a serum LDL cholesterol greater than or equal to 130 mg/dL plus a serum high-density lipoprotein (HDL) cholesterol < 50 mg/dL. Gemfibrozil may be useful in reducing the incidence of coronary events in persons with coronary artery disease whose primary lipid abnormality is a low serum HDL cholesterol level. There are no good data supporting treatment of hypertriglyceridemia unassociated with increased LDL cholesterol or decreased HDL cholesterol for prevention of cardiovascular disease.
Am J Geriatr Cardiol
PMID:Pharmacologic therapy of lipid disorders in the elderly. 1209 73

This retrospective study was carried out to assess the effectiveness of statin-gemfibrozil combination therapy in a community practice lipid clinic and to review safety data from published literature. Forty-six consecutive patients received a statin and gemfibrozil combination for resistant hyperlipidemia to either agent therapy. Fasting total cholesterol (mg/dL), high-density lipoprotein cholesterol (mg/dL), and triglycerides (mg/dL) were measured. Low-density lipoprotein cholesterol (mg/dL) was calculated using the Friedewald formula if triglycerides were <400 mg/dL. Combination therapy reduced total cholesterol, low-density lipoprotein cholesterol, and triglycerides by 11% (p=0.02), 22% (p=0.049), and 39% (p=0.0002), respectively, and raised high-density lipoprotein cholesterol by 5% (p=0.3). A pooled analysis of 838 patients from the literature on statin-gemfibrozil combination therapy revealed an incidence of myositis and severe myopathy of 0.7% and 0.6%, respectively (excluding cerivastatin). We conclude that statin-gemfibrozil combination therapy is effective in significantly reducing total cholesterol, low-density lipoprotein cholesterol, and triglycerides with a trend toward raising high-density lipoprotein cholesterol in patients with hyperlipidemia resistant to either agent alone. Myositis and severe myopathy are infrequent, but not rare side effects which may be statin-specific regarding the incidence of occurrence.
Prev Cardiol 2003
PMID:Effectiveness of statin-gemfibrozil combination therapy in patients with mixed hyperlipidemia: experience of a community lipid clinic and safety review from the literature. 1460 12

Statin therapy (3-hydroxy-3methylglutaryl coenzyme A reductase inhibitor) is beneficial for primary prevention of cardiovascular events in patients younger than age 65 years with hyperlipidemia, yet there is uncertainty about using these agents for primary prevention in octogenarians. We present the case that can be made for not treating octogenarians with statins for the primary prevention of cardiovascular disease. This case is built on three points: 1) cholesterol levels are not associated with cardiovascular disease events in octogenarians without overt coronary artery disease; 2) no randomized, controlled trials have assessed the role of statins in reducing events in octogenarians without coronary artery disease; and 3) statins may increase risks of myositis, rhabdomyolysis, and cancer in the elderly. In view of gaps in the current evidence and the resulting clinical uncertainty, it is unclear whether the balance of risk and benefit favors treatment for the primary prevention of coronary artery disease in octogenarians. The use of statins in this age group should be based on patient preference.
Am J Geriatr Cardiol
PMID:Are statins indicated for the primary prevention of CAD in octogenarians? antagonist viewpoint. 1461 Mar 84

Pharmacologic lipid-lowering interventions should be monitored periodically to assess efficacy and safety parameters. Statins are usually well-tolerated drugs and major side effects include increased serum liver and muscle enzymes (AST, ALT, CK). Treatment should be stopped or diminished in case of significant increase of AST or ALT (> 3x ULN), or CK (> 10x ULN). Other lipid lowering agents may also produce hepatotoxicity or myositis, especially in association with statins (fibrates and nicotinic acid) or in presence of metabolic abnormalities (thyroid, liver or renal disorders). Nicotinic acid can also increase glucose and uric acid plasma levels. Laboratory tests might be performed prior to hypolipidemic drug treatment and should be repeated every three months during the first year and then at 6-mo intervals. Shorter intervals should be recommended in individual cases.
Arq Bras Cardiol 2005 Oct
PMID:[Special recommendations for lipid-lowering treatment: efficacy and safety]. 1640 Mar 89

Myositis is an infrequent side effect of statin therapy, usually presenting as diffuse myositis with muscle weakness and cramping involving multiple body parts. We report a case of focal myositis of a hip muscle diagnosed on magnetic resonance imaging, as the underlying pathology was suspected to be related to an orthopaedic disease due to isolated hip symptoms, and which was finally attributed to statin intake. Awareness to this rare cause of musculoskeletal symptoms is indicated in case a patient presents with probable orthopaedic disease and is on statin therapy.
Int J Cardiol 2009 Mar 20
PMID:Statin-associated focal myositis. 1815 87

Fibrates are a class of lipid-lowering medication primarily used as second-line agents behind statins. Acting via the peroxisome proliferators-activated receptor-alpha, their main lipoprotein effects are to lower serum triglyceride levels and to raise high-density lipoprotein-cholesterol, with modest effects on low-density lipoprotein-cholesterol. However, many clinical trials indicate that fibrates may have benefits beyond simply altering one's lipid profile. Several angiographic studies show retardation in the progression of atherosclerotic lesions in coronary vessels. Although clinical trials have failed to show a reduction in mortality with fibrates, several post hoc analyses indicate that there may be a mortality benefit in patients with features of the metabolic syndrome. Given that fibrates are often used as second-line agents, it is essential they are safe to be given in combination with other agents, particularly statins and ezetimibe. Although the side-effect profile of fibrates includes gastrointestinal symptoms, increased liver function tests, a reversible rise in creatinine and myositis, in general, fibrates seem to be safe to use in combination with other lipid lowering medications. Thus far, fibrates have not shown a mortality benefit in randomized clinical trials; as a result, they cannot be considered first-line medication for the primary or secondary prevention of coronary artery disease.
Cardiol Rev
PMID:Fibrate therapy: an update. 1841 84


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