Long-Term Clinical Tolerance of Lovastatin and Simvastatin

Bilheimer, David W.

doi:10.1159/000174684

Cited by 23 publications

(10 citation statements)

References 11 publications

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“…The frequency of adverse events was dose-dependent and consistent with previous reports [9,19,[26][27][28]. The number of patients with adverse reactions (16.6%) should be viewed against the reported frequency of about 10-20% adverse events in subjects treated with placebo [29,30].…”

Section: Discussionsupporting

confidence: 88%

“…Other adverse events involving the nervous and mnsculoskeletal systems, and general symptoms such as fatigue and insomnia have been reported with similar frequencies [9,19,27,31]. Small increases in transaminases, particularly A1T, have been observed repeatedly during treatment with HMG-CoA reductase inhibitors [4,8,9,19,26,27]. In this study, the frequency of patients with increased A1T and AsT values (0.1% > 3 x ULN) was not higher than in trials with lovastatin (0.1-1.5 % ) [29].…”

Section: Discussionmentioning

confidence: 99%

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Prediction of the therapeutic response to simvastatin by pretreatment lipid concentrations in 2082 subjects

Miserez

Rossi²,

Keller

1994

Eur J Clin Pharmacol

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2082 hypercholesterolemic subjects were treated with simvastatin for 12 weeks. In 530 patients the dose was increased after 6 weeks from 10 to 20 mg because of persistently high cholesterol concentrations. Total cholesterol (TC) in the 1552 patients taking 10 mg fell by 1.61 mmol.l-1 (18.4%), LDL cholesterol (LDLC) by 1.53 mmol.l-1 (25.2%), and triglycerides (TG) by 0.13 mmol.l-1 (5.5%); HDL cholesterol (HDLC) significantly increased by 0.05 mmol.l-1 (3.6%). In the 530 patients taking 20 mg TC fell by 1.89 mmol.l-1 (19.9%), LDLC by 1.78 mmol.l-1 (26.0%), and TG by 0.13 mmol.l-1 (5.5%); HDLC increased by 0.05 mmol.l-1 (3.7%). The reductions in TC, LDLC, and TG were positively correlated and the increase in HDLC negatively correlated with their respective baseline values. There were independent significant correlations of the fall in LDLC with sex (MANOVA), baseline TG, and adherence to a lipid-lowering diet. The falls in TG significantly correlated with baseline fructosamine concentrations and dietary adherence. There were 571 adverse events in 16.6% of the patients but no case of myopathy. These results show that simvastatin is usually well tolerated and that its effects on TC and LDLC depend on their baseline concentrations.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Prediction of the therapeutic response to simvastatin by pretreatment lipid concentrations in 2082 subjects

Miserez

Rossi²,

Keller

1994

Eur J Clin Pharmacol

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“…Subsequently, the second agent, sim vastatin, was approved and marketed in a number of countries. These two lactone pro drugs, which are very effective in controlling hypercholesterolemia, have a good tolerabil ity profile [ 12], and are associated with good patient compliance.…”

mentioning

confidence: 99%

Lovastatin and Simvastatin - Inhibitors of HMG CoA Reductase and Cholesterol Biosynthesis

Alberts¹

1990

Cardiology

106

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The microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is a key rate-controlling step early in the cholesterol biosynthetic pathway that catalyzes the conversion of HMG CoA to mevalonic acid. Since this enzyme plays a significant role in regulating cholesterol synthesis, it is a rational target for pharmacologic intervention. The first potent, specific inhibitor of HMG CoA was mevastatin (compactin, ML-236B) which was discovered in 1976 by Endo et al. [J Antibiot 1976;29:1346-1348]. Subsequently, lovastatin, a novel, more active fungal metabolite was isolated from a strain of Aspergillus terreus.Lovastatin, the first of this class of agents to be approved for clinical use, was chemically modified to form simvastatin. Simvastatin is superior to lovastatin in intrinsic inhibitory potency. Both are inactive lactone prodrugs that must be converted to their respective dihy-droxy open-acid forms to elicit inhibitory activity. Pharmacologic characterization of lovastatin and simvastatin has demonstrated that these potent inhibitors of HMG CoA reductase specifically inhibit cholesterol synthesis in animal cells, as well as in vivo after oral administration of the agents. Oral administration of either lovastatin or simvastatin to dogs in the presence or absence of the bile acid sequestrant cholestyramine results in a marked, sustained lowering of plasma cholesterol. Associated with the cholesterol lowering is a decrease in urinary and plasma levels of mevalonic acid, the end product of the HMG CoA reductase reaction. The target organ for inhibitors of HMG CoA reductase is the liver, the primary site of cholesterol biosynthesis. Both lovastatin and simvastatin are preferentially extracted by this organ. In studies in the rat in which direct measurements of drug levels have been carried out, much more inhibitory activity derived from the prodrugs lovastatin and simvastatin is found in the liver than in spleen, testes, and kidney. This is reflected in a much greater in vivo inhibition of cholesterol synthesis in the liver by these agents than in the periphery. In summary, the HMG CoA reductase inhibitors lovastatin and simvastatin are potent inhibitors of mevalonic acid synthesis in vitro and in vivo. They are preferentially concentrated in the liver, the target organ. This results in inhibition of cholesterol synthesis and a concomitant decrease in plasma low-density lipoprotein cholesterol in experimental animals and humans.

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“…Bilheimer (1990) assessed the long term tolerability oflovastatin in 744 patients. After 5 years the drug had been discontinued in 2.3% of patients because of drug-related adverse events (elevated liver enzymes 1.3%, rash 0.4%, persistent gastrointestinal symptoms 0.3%, myopathy 0.1 %, insomnia 0.1 %).…”

Section: Tolerabilitymentioning

confidence: 99%

HMG-CoA Reductase Inhibitor Use in the Aged

Lintott

Scott

1992

Drugs & Aging

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While the benefit of cholesterol-lowering in the elderly has yet to be proven in clinical trials, individuals at high risk of coronary events who otherwise enjoy a good quality of life, should not be denied cholesterol-lowering therapy on the basis of age alone. Moreover, hypolipidaemic drugs are already extensively used in the aged. The HMG-CoA reductase inhibitors lovastatin, simvastatin and pravastatin are potent well tolerated hypolipidaemic therapies in young subjects. Although there have been few studies on their use in elderly subjects, the available data suggest the efficacy and safety of HMG-CoA reductase inhibitors in similar to that established for younger age groups.

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Long-Term Clinical Tolerance of Lovastatin and Simvastatin

Cited by 23 publications

References 11 publications

Prediction of the therapeutic response to simvastatin by pretreatment lipid concentrations in 2082 subjects

Prediction of the therapeutic response to simvastatin by pretreatment lipid concentrations in 2082 subjects

Lovastatin and Simvastatin - Inhibitors of HMG CoA Reductase and Cholesterol Biosynthesis

HMG-CoA Reductase Inhibitor Use in the Aged

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