HMG-CoA Reductase Inhibitors and Myotoxicity

Ucar, Memduh; Mjörndal, Tom; Dahlqvist, Rune

doi:10.2165/00002018-200022060-00003

Cited by 252 publications

(170 citation statements)

References 107 publications

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“…Increases in CPK level have been observed with lipid-lowering therapies, particularly high doses of statins or upward dosage titration. 17 Coadministration of ezetimibe with low-dose atorvastatin was a well-tolerated option to high-dose atorvastatin monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia

et al. 2003

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Background-Despite the established efficacy of statins, many patients do not achieve recommended LDL cholesterol (LDL-C) goals. Contributing factors may be inadequate dosing, increased risk for adverse effects with high-dose monotherapy, and increased potential for intolerance and adverse effects with combinations of available agents. Methods and Results-In a double-blind study, 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides Յ350 mg/dL were randomly assigned to receive 1 of the following for 12 weeks: ezetimibe ( Coadministration of ezetimibe provided a significant additional 12% LDL-C reduction, 3% HDL-C increase, 8% triglyceride reduction, and 10% hs-CRP reduction versus atorvastatin alone. Ezetimibe plus atorvastatin provided LDL-C reductions of 50% to 60%, triglyceride reductions of 30% to 40%, and HDL-C increases of 5% to 9%, depending on atorvastatin dose. LDL-C reductions with ezetimibe plus 10 mg atorvastatin (50%) and 80 mg atorvastatin alone (51%) were similar. Conclusions-Ezetimibe plus atorvastatin was well tolerated, with a safety profile similar to atorvastatin alone and to placebo. When coadministered with atorvastatin, ezetimibe provided significant incremental reductions in LDL-C and triglycerides and increases in HDL-C. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with hypercholesterolemia. (Circulation. 2003;107:2409-2415.)

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Section: Discussionmentioning

confidence: 99%

Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia

et al. 2003

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“…The monitoring of CK levels is considered a useful parameter in tracing myotoxicity in patients using anti-lipemics 3,8 , including those who are assymptomatic 5,6 , although there are reports of confirmed toxic myopathy cases with normal muscle biopsy and normal CK 12 . A rise in CK during therapy with statins is well documented, ranging between 0.1% and 10% 6 , usually not exceeding 10 times over the upper limit of normal 3,5 .…”

Section: Discussionmentioning

confidence: 99%

“…The most severe risk of these drugs is myositis with rhabdomyolysis. Rapid remission of symptoms after discontinuation of therapy has frequently been reported [1][2][3][4][5][6][7][8][9] .…”

mentioning

confidence: 99%

Statin and fibrate associed myopathy: study of eight patients

Carvalho

Lima

Valiente

2004

Arq. Neuro-Psiquiatr.

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-Lipid-lowering drugs have been occasionally associated with neuromuscular symptoms and muscle biopsy changes. We reported the clinical course and the muscle biopsy in eight patients with hyperlipoproteinemia, treated with lipid -lowering drugs (statins/fibrates). Five patients had myalgias while; in two cases there was proximal muscle weakness. All patients became asymptomatic after the withdrawal of the drug, although creatine kinase remained elevated. We performed muscle biopsy in six cases from three months to two years after suspension of the drug. We found variation in fibers diameters in all cases, with necrosis of fibers in five cases, inflammatory infiltration in one case, the presence of vacuolated fiber in one patient and ragged-red fibers in three subjects. We concluded that although the muscle biopsy findings were not specific, the prolonged use of statins and or fibrates might induce a chronic myopathy even in the absence of symptoms.KEY WORDS: statins, fibrates, myopathy, muscle biopsy, creatine kinase. Miopatia associada a estatina e fibrato: estudo de oito pacientesRESUMO -As drogas redutoras de colesterol são ocasionalmente associadas a sintomas neuromusculares e alterações morfológ-icas observadas na biopsia muscular. Relatamos o curso clínico e achado da biopsia muscular em oito pacientes com hiperlipoproteinemia tratados com drogas redutoras de colesterol (estatinas/fibratos). Cinco pacientes tiveram mialgia e em dois havia fraqueza muscular proximal.Todos os pacientes ficaram assintomáticos após retirada da medicação embora a creatinoquinase permanecesse elevada. Analisamos a biopsia muscular em seis casos realizados entre três meses e dois anos após a suspensão da droga. Encontramos variação no calibre das fibras em todos os casos com necrose de fibras em cinco, infiltrado inflamatório em um caso, presença de vacúolos em um e "ragged red fiber" em três deles. Concluímos que, embora os achados da biopsia muscular não fossem específicos, o uso prolongado de estatinas e/ou fibratos pode induzir a uma miopatia crônica até mesmo na ausência de sintomas.

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“…Apoptosis is a critical mechanism in the remodelling and maintenance of tissue structure and inappropriate apoptosis can produce pathological conditions (121,122) . Some of the decrease in CoQ 10 can probably be explained by the reduction in LDL-cholesterol levels after statin therapy, since CoQ 10 is transported in the LDL particle (121) .…”

Section: Effects Of Combination Therapy With Coenzyme Q 10 and Statinsmentioning

confidence: 99%

Support of drug therapy using functional foods and dietary supplements: focus on statin therapy

et al. 2010

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Functional foods and dietary supplements might have a role in supporting drug therapy. These products may (1) have an additive effect to the effect that a drug has in reducing risk factors associated with certain conditions, (2) contribute to improve risk factors associated with the condition, other than the risk factor that the drug is dealing with, or (3) reduce drug-associated side effects, for example, by restoring depleted compounds or by reducing the necessary dose of the drug. Possible advantages compared with a multidrug therapy are lower drug costs, fewer side effects and increased adherence. In the present review we have focused on the support of statin therapy using functional foods or dietary supplements containing plant sterols and/or stanols, soluble dietary fibre, n-3 PUFA or coenzyme Q 10 . We conclude that there is substantial evidence that adding plant sterols and/or stanols to statin therapy further reduces total and LDL-cholesterol by roughly 6 and 10 %, respectively. Adding n-3 PUFA to statin therapy leads to a significant reduction in plasma TAG of at least 15 %. Data are insufficient and not conclusive to recommend the use of soluble fibre or coenzyme Q 10 in patients on statin therapy and more randomised controlled trials towards these combinations are warranted. Aside from the possible beneficial effects from functional foods or dietary supplements on drug therapy, it is important to examine possible (negative) effects from the combination in the long term, for example, in post-marketing surveillance studies. Moreover, it is important to monitor whether the functional foods and dietary supplements are taken in the recommended amounts to induce significant effects. Combination therapy: Dyslipidaemia: Statins: Functional foodsThe world market for functional foods (FF) and dietary supplements (DS) is expanding rapidly. In 2010 FF are expected to represent 5 % of the total global food market (1) and the market for DS is estimated at more than $60 billion worldwide (2) . In general, the target population of FF or DS is healthy individuals with slightly elevated risk factors or some physical discomfort. However, due to the fast growing market of FF or DS and the accompanying strong advertising and marketing, also patients on medication may be stimulated to use FF or DS. This may have several consequences for the quality of drug treatment as stated by de Jong et al. with the example of the combined intake of plant sterols and/or stanols and statins (3) . Whereas they addressed the additive effect of plant sterols and/or stanols on reducing LDL-cholesterol values in patients on statin treatment, their main focus was the possible negative aspects of the combination, such as unfavourable effects on patient adherence with drug treatment and increasing the potential for food-drug interactions.In the present review we will focus on the possible beneficial effects that FF or DS may have on drug therapy. Because of the large number of subjects treated suboptimally with statins (hydroxymethylglutaryl Co...

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HMG-CoA Reductase Inhibitors and Myotoxicity

Cited by 252 publications

References 107 publications

Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia

Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia

Statin and fibrate associed myopathy: study of eight patients

Support of drug therapy using functional foods and dietary supplements: focus on statin therapy

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