Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial

McCarey, David; McInnes, Iain B.; Madhok, Rajan; Hampson, Rosie; Scherbakova, Olga; Ford, Ian; Capell, Hilary A.; Sattar, Naveed

doi:10.1016/s0140-6736(04)16449-0

Cited by 722 publications

(306 citation statements)

References 35 publications

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“…Measures related to quality of life have also been assessed in randomized controlled trials of statin therapy in specific types of patient (e.g. those with rheumatoid arthritis, systemic lupus erythematosus, peripheral arterial disease, and erectile dysfunction), [263][264][265][266] with no good evidence of any adverse effects on any of these measures. Nor was there evidence for an adverse effect of statin therapy in a meta-analysis of randomized trials that assessed psychological outcomes.…”

Section: Quality Of Life Related Measuresmentioning

confidence: 99%

Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms SummaryThis review is intended to help clinicians, patients and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomized controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment.Large-scale randomized trial evidence shows that statin therapy reduces the risk of heart attacks, ischaemic strokes and coronary revascularization procedures ("major vascular events") by about one quarter for each mmol/L reduction in low density lipoprotein (LDL) cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (e.g. atorvastatin 40 mg daily, costing about £2 per

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Section: Quality Of Life Related Measuresmentioning

confidence: 99%

Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

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“…A larger randomized placebo-controlled study investigating atorvastatin as a disease-modifying antirheumatic drug (DMARD) in RA (Trial of Atorvastatin in Rheumatoid Arthritis) also showed modest effects (155). In this 116-patient study, patients received either 40 mg of atorvastatin per day or placebo in addition to current DMARD therapy; DMARDs were not allowed to be changed during the 6-month study.…”

Section: Statin Trials In Human Inflammatory and Autoimmune Diseasesmentioning

confidence: 99%

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

Abeles

Pillinger

2006

Arthritis & Rheumatism

136

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“…For example, in the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy -Thrombolysis in Myocardial Infarction 22) study, the benefits of statin therapy in patients with acute coronary syndrome were observed within 30 days of treatment [14]. Furthermore, statins appear to have therapeutic benefits in diseases that are unrelated to elevated serum cholesterol levels, such as rheumatologic diseases [19] and ischemic stroke [1]. These findings suggest that statins might exert beneficial effects beyond cholesterol reduction.…”

Section: Clinical Trials With Statinsmentioning

confidence: 99%

“…Clinical trials have demonstrated that statins can reduce morbidity in patients with multiple sclerosis [35,36]. Furthermore, in a 6 month, randomized, double-blind placebocontrolled clinical trial, patients with rheumatoid arthritis who received atorvastatin showed a reduction in disease activity [19]. However, it is too early to predict whether these promising data can translate into clinical benefit by statins in patients with autoimmune disease.…”

Section: Clinical Trials With Statinsmentioning

confidence: 99%

Pleiotropic effects of statin therapy: molecular mechanisms and clinical results

Wang

Liu

Liao

2008

Trends in Molecular Medicine

537

394

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Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for cholesterol biosynthesis, and are beneficial in the primary and secondary prevention of cardiovascular disease. Most of the benefits of statin therapy are owing to the lowering of serum cholesterol levels. However, by inhibiting HMG-CoA reductase, statins can also inhibit the synthesis of isoprenoids, which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42. Therefore, it is possible that statins might exert cholesterol-independent or 'pleiotropic' effects through direct inhibition of these small GTP-binding proteins. Recent studies have shown that statins might have important roles in diseases that are not mediated by cholesterol. Here, we review data from recent clinical trials that support the concept of statin pleiotropy and provide a rationale for their clinical importance. [6], have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. Because 60-70% of serum cholesterol is derived from hepatic synthesis and HMG-CoA reductase is the crucial, rate-limiting enzyme in the cholesterol biosynthetic pathway, inhibition of this enzyme by statins results in a dramatic reduction in circulating low-density lipoprotein (LDL)-cholesterol (Figure 1). In addition, reduction of LDL-cholesterol leads to upregulation of the LDL receptor and increased LDL clearance. The lowering of serum cholesterol levels is therefore thought to be the primary mechanism underlying the therapeutic benefits of statin therapy in cardiovascular disease [1]. Pleiotropy of statins: beyond cholesterol loweringStatins, however, might also exert cholesterol-independent or pleiotropic effects. By inhibiting the conversion of HMG-CoA to L-mevalonic acid, statins prevent the synthesis of important isoprenoids, such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP), which are precursors of cholesterol biosynthesis [7] (Figure 1). These intermediates serve as important lipid attachments for the post-translational modification of proteins, such as nuclear lamins, Ras, Rho, Rac and Rap [8]. These isoprenylated proteins constitute approximately 2% of total cellular proteins [9]. Protein isoprenylation (see Glossary) enables proper subcellular localization and trafficking of intracellular proteins. Given that isoprenylated proteins might

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Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial

Cited by 722 publications

References 35 publications

Interpretation of the evidence for the efficacy and safety of statin therapy

Interpretation of the evidence for the efficacy and safety of statin therapy

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

Pleiotropic effects of statin therapy: molecular mechanisms and clinical results

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