SEARCH · Search PubMed

Results for “Statins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed2004

[Ezetimibe (Ezetrol): the statins' partner].

Ezetimibe is a new cholesterol absorption inhibitor that selectively inhibits dietary and biliary cholesterol absorption from the intestine. This drug inhibits cholesterol absorption without affecting the absorption of triglycerides, biliary salts and fat-soluble vitamins. Inhibition of cholesterol absorption using ezetimibe 10 mg/day alone resulted in substantial reductions of plasma LDL-C concentrations (approximately 18%). Coadministration of ezetimibe 10 mg/day with statins 10 mg/day showed LDL lowering comparable to or greater than that of the highest dose of the respective statin alone. Combination therapy of ezetimibe with statins helped more patients in achieving their target LDL-C goal. Ezetimibe in coadministration with statins or alone had also favourable effects on triglycerides and HDL. In clinical studies, ezetimibe alone or coadministered with a statin was shown to have a safety profile (asymptomatic mild increases in aminotransferase levels, without evidence of rhabdomyolysis) similar to placebo or to the statin alone. Large clinical studies on clinical endpoints are in progress.

Animals↗

PubMed2005

Association of statin use and development and progression of hip osteoarthritis in elderly women.

OBJECTIVE: . To examine the association between use of HMG CoA reductase inhibitor (statin) and development and progression of radiographic findings of hip osteoarthritis (OA) in elderly women. METHODS: Baseline and followup anteroposterior pelvic radiographs were obtained, a mean of 8 years apart, in 5674 women (69% of the total survivors) age 65 years and older from the Study of Osteoporotic Fractures. Hips were scored for individual radiographic features (IRF) and assigned a summary grade of radiographic hip osteoarthritis (RHOA) based on the number and type of IRF present. Statin use was recorded from prescription labels provided by participants at Year 6 and Year 8 of followup. We estimated odds ratios for the development of RHOA in hips without disease at baseline and for progression of RHOA in hips with baseline disease, using generalized estimating equations to account for correlations of right and left hips. RESULTS: RHOA was present in 936 hips of 745 women at baseline and there were 9318 hips without baseline RHOA. Overall, 7% of women in this cohort were statin users. Statin use was associated with increased odds of developing incident summary grade > or = 3 RHOA (OR 1.92, 95% CI 1.03-4.43, p = 0.045), but was not significantly related to other measures of new RHOA. In hips with baseline RHOA there was a consistent but nonsignificant trend toward decreased progression of RHOA in statin users (all OR between 0.69 and 0.76, with 95% CI between 0.29 and 1.67). CONCLUSION: Statin use may be associated with an increased risk of developing incident RHOA but does not adversely influence progression of established disease.

Aged↗

PubMed2005

Prescribing of contraindicated protease inhibitor and statin combinations among HIV-infected persons.

HIV-1 protease inhibitors (PIs) contribute to hyperlipidemia in persons treated for HIV infection. There are potential drug-drug interactions between PIs and some statins, which are drugs frequently used to treat hyperlipidemia. We performed a retrospective cohort study using the TennCare program to determine prescribing rates of contraindicated combinations of PIs and statins in HIV-infected persons in Tennessee and to assess changes in prescribing after publication of treatment guidelines. Computerized files identified adult patients with antiretroviral prescriptions and overlapping prescriptions for PIs and statins from January 1, 1996 through June 30, 2002. A subset of these combinations was defined as contraindicated based on published guidelines. Changes in patterns of prescribing after publication of preliminary treatment guidelines were examined using a mixed-effects logistic regression model. There were 3448 persons who received PIs during the study period. The proportion of PI users receiving statins increased from 3.5% during January 1996 through December 2000 to 7.9% during January 2001 through June 2002 (P < 0.001). Contraindicated PI-statin use decreased from 42.0% of combinations to 20.8% during the same periods (P < 0.001). Use of PIs and statins has increased in the adult TennCare population. Contraindicated combinations have decreased but remain unacceptably high.

Adolescent↗

PubMed2003

Regulation of osteoclast differentiation by statins.

HMG-CoA reductase inhibitor (statin) treatment is frontline therapy for lowering plasma cholesterol levels in patients with hyperlipidemia. In a few case studies, analysis of clinical data has revealed a decreased risk of fracture in patients on statin therapy. However, this reduction in the incidence of fracture is not always observed nor is it supported by an increase in bone density, which further complicates our understanding of the role of statins in bone metabolism. Thus, the precise role of statins in bone metabolism remains poorly understood. In this study, we examined the effect of statin treatment on osteoclastogenesis. Treatment with lovastatin resulted in a significant, dose-dependent decrease in the numbers of differentiated osteoclasts and decreased cholesterol biosynthesis activity with an EC(50) similar to that observed in freshly isolated rat or cultured human liver cells. Studies assessing the role of mevalonate metabolites in the development of the osteoclasts demonstrated that geranylgeraniol, but not squalene or farnesol was important for the development and differentiation of osteoclasts, implicating protein geranylgeranylation rather than protein farnesylation as a key factor in the osteoclast differentiation process. In conclusion, our data indicate that lovastatin inhibits osteoclast development through inhibition of geranylgeranylation of key prenylated proteins and that the bone effects of statins are at least partially due to their effects on osteoclast numbers.

Journal Article↗

PubMed2004

Statins and osteoporosis: myth or reality?

Several beneficial effects produced by statins over and above the reduction in plasma cholesterol levels, the so-called ''pleiotropic effects'' of statins, have been described. Recent clinical and experimental data have suggested a potential new effect of these drugs, namely a reduction in the risk of osteoporotic fractures. In 1999 the role of statins in bone formation was shown and, after that, observations of large groups of patients have pointed to a reduction in the risk of osteoporotic fractures with the use of statins compared to those using other lipid-lowering drugs or to the control group. The first prospective studies have produced contrasting results as to the effects of therapy with several statins (atorvastatin, fluvastatin, simvastatin) at different doses on biochemical markers of bone remodelling. To date only one randomised trial has been published. This compares the effects of treatment with simvastatin and atorvastatin on the levels of biochemical markers of bone remodelling, but still with non-univocal results: only therapy with simvastatin (but not atorvastatin) reduced the levels of bone-specific alkaline phosphatase. To conclude, observational studies have shown a reduction in the risk of osteoporotic fractures with the use of statins, but it is not yet known whether using these drugs may have a beneficial effect on bone turnover. We must therefore await larger prospective randomised clinical trials before prescribing these drugs in osteoporotic patients.

Anticholesteremic Agents↗

PubMed2005

[Local application of statin for bone augmentation].

It has been reported that statin, an inhibitor of cholesterol synthesis, enhances bone formation by stimulating osteoblastic differentiation and function and that it also inhibits bone resorption by osteoclasts. Although the potentiality of statin as a therapeutic drug for osteoporosis has been expected, the clinical evidences supporting this potentiality are few. On the other hand, there are several reports demonstrating that local application of statin promotes bone augmentation and bone regeneration. The history of statin as a therapeutic drug for hypercholesterolemia is long and the toxicity of this drug has been well examined. Thus, it is unlikely that local application of this drug at low dose will induce serious side effects. It is possible that local bone augmentation with statin will appear clinically in the near future if proper local drug delivery system for statin is developed.

Animals↗

PubMed2005

Pleiotropic effects of statins in atherosclerosis: role on endothelial function, inflammation and immunomodulation.

Atherosclerosis and its complications still represent the major cause of death in developed countries. Statins have been described as the most potent class of drugs to reduce serum cholesterol levels. The effectiveness and rapidity of statin-induced decreases in coronary events led to the speculation that statins possess also cholesterol-independent effects. By the inhibition of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol synthesis, statins reduce not only cholesterol but also non steroidal isoprenoid intermediates production. Since these isoprenoids, such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, regulate the small signaling proteins, Ras and Rho, inhibition of these prenylated proteins by statins might account for their non-lipid-related effects. In this review, we describe the numerous beneficial pleiotropic effects of statins that could modulate atherogenesis.

Arteriosclerosis↗

PubMed2005

Stimulatory effects of statins on bone marrow-derived mesenchymal stem cells. Study of a new therapeutic agent for fracture.

Recent studies have reported that statins, inhibitors of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, increase bone formation in osteoblasts in vitro, suggesting that statins may have a new therapeutic application in the treatment of osteoporosis. During the reparative phase of healing of bone fractures, bone marrow-derived mesenchymal stem cells differentiate into osteoblasts or chondrocytes to form callus. If statins also stimulate bone formation in bone marrow-derived mesenchymal stem cells they may have beneficial effects in the treatment of bone fractures. In this study, we assessed the effect of statins on bone formation in rat bone marrow-derived mesenchymal stem cells in vitro. The statins fluvastatin, simvastatin and pravastatin did not significantly enhance mineralization, alkaline phosphatase (ALP) activity and bone gra protein (BGP, osteocalcin). These findings suggest that statins do not increase bone formation in bone marrow-derived mesenchymal stem cells.

Animals↗

PubMed2005

HMG-CoA reductase inhibitors (statins) as anticancer drugs (review).

Apart from their lipid lowering activity, HMG-CoA reductase inhibitors (statins) impair numerous cellular functions associated with metastasis, e.g. gene expression, angiogenesis, cell adhesion, cell motility and invasiveness. Furthermore, statins have impact on apoptotic cell death and modulate cellular susceptibility to cell killing by anticancer drugs and ionizing radiation. Part of the effects provoked by statins are due to the inhibition of the prenylation of low molecular weight GTPases, in particular Ras and Rho, which play key roles in signaling evoked by stimulation of cell surface receptors. C-terminal lipid modification of Ras/Rho GTPases is essential for their correct intracellular localization and function. By depletion of the cellular pool of isoprene precursor molecules, statins reduce the level of membrane-bound active Ras/Rho proteins, thereby impairing corresponding functions. Since broad clinical experience already exists for statins, their incorporation into established tumor-therapeutic regimens would be realizable in a rather short period of time. Here, data available at present arguing for the usefulness of statins in anticancer therapy are summarized and discussed.

Cell Adhesion↗

PubMed2005

The effect of switching on compliance and persistence: the case of statin treatment.

OBJECTIVE: To determine the effect of switching drugs on the compliance and persistence of new statin users. STUDY DESIGN: Retrospective database analysis of pharmacy claims provided by a large pharmacy benefit manager. The study sample consisted of 38 866 new statin users 18 to 65 years old beginning treatment with atorvastatin calcium, fluvastatin sodium, lovastatin, pravastatin sodium, or simvastatin. METHODS: Compliance was measured by the "medication possession ratio," and persistence was measured by the time to discontinuation. Switching rates were derived from the proportions of patients filling a prescription other than the initial statin. RESULTS: Patients who switched statins were less compliant by 18.9% (odds ratio, 0.81; P < .001), as defined by the probability of having a medication possession ratio of 0.8 or higher, and were less persistent by 20.9% to 48.3% (P < .001) depending on the gap length used to define discontinuation. CONCLUSIONS: Switching statins substantially reduces the likelihood that patients will be compliant and remain on treatment long enough to obtain the full benefit of statin treatment. To ensure better compliance, special care should be given to patients who change drugs.

Adolescent↗

PubMed2005

[Erythrocyte fluidity in patients with hyperlipidemia during statins therapy].

UNLABELLED: The lipid composition of erythrocyte membrane is in a state of dynamic equilibrium with plasma lipoproteins and reflects the processes taking place in extracellular environment. The recent studies were devoted to the phenomenon of modification of atherosclerosis development by statins. The aim of the study was evaluation of three statins: simvastatin, atorvastatin and pravastatin on plasma lipidogram and fluidity of erythrocytes membranes in patients (pts) with hyperlipidemia (hlp) type II. INVESTIGATED GROUP: the study comprised 114 pts, including 94 pts with hlp type II without concomitant chronic diseases and 20 healthy volunteers. Pts were qualified to treatment with statins if their LDL-cholesterol concentration (LDL-C) was above 170 mg/dL (4,1 mmol/L), total cholesterol (TC) > 250 mg/dL (6,5 mmol/L) and triglicerydes (TG) < 400 mg/dL (4,5 mmol/L). Pts were randomised to three groups: group I-n = 31 pts treated with atorvastatin (10 mg/d); group Il-n = 31 with simvastatin (20 mg/d), group III-n = 32 with pravastatin (20 mg/d). METHODS: after 4 and 12 weeks of active treatment the following parameters were determined: TC, HDL-C, TG (by enzymatic method using BioMerieux tests); LDL-C was calculated from the Friedewald formula and erythrocyte membranes fluidity by electron paramagnetic resonance with two spin labels (5-DSA, 16-DSA). RESULTS: During statin therapy significant decrease of TC, LDL-C, TG was observed, both after 4 and 12 weeks, as compared with initial values. All statins after 4 weeks of therapy caused a significant increase of membrane fluidity in its surface layer at carbon 5 depth. The values of parameter S after 12 weeks did not differ significantly from the values in the control group. The percent decrease of membrane microviscosity at carbon 5 depth did not correlate significantly with percent changes plasma TC and LDL-C. Atorvastatin appeared to be the strongest drug liquidizing erythrocytes membranes. There were no significant changes in fluidity of membrane in its deeper layers (at carbon 16 level). CONCLUSION: Statins therapy was beneficial not only for modification of plasma lipids but caused the increase of erythrocytes membrane fluidity in the surface layer.

Adult↗

PubMed2006

Statin-mediated protective effects in the central nervous system: general mechanisms and putative role of stress proteins.

PURPOSE: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins", are used as cholesterol-lowering agents worldwide. This review, focused on recent experimental and clinical data, summarizes general mechanisms of statin actions underlying neuroprotective effects in the central nervous system (CNS) and presents evidence for putative mechanisms involving heat shock proteins and the survival-related PI-3K/Akt pathway that may be beneficial for the treatment of neurological disorders. METHODS: We carried out a medline search on statin actions, with respect to biochemical pathways and signal transduction on the one hand, and clinical studies in neurologic and retinal diseases on the other hand. Novel experimental data obtained in a rat model of axonal CNS injury were also included. RESULTS: Statins exert multiple effects on endothelial function, cell proliferation, inflammatory response, immunological reactions, platelet function, and lipid oxidation. These "pleiotropic actions" are independent of cholesterol lowering and appear to be beneficial in the context of brain injury. Several mechanisms of statin actions underlying neuroprotective effects may also involve heat shock proteins and the survival-related PI-3K/Akt pathway. CONCLUSIONS: Available data suggest that statins may be of potential therapeutic use in a variety of diseases of the CNS including ischemic stroke, Alzheimer's disease, multiple sclerosis and some forms of retinal and eye diseases. Before general recommendations can be made and specific therapeutic approaches can be developed, more reliable clinical data and studies are required, and possible side effects must be carefully evaluated.

Animals↗

PubMed2006

Cost effectiveness of statin therapy for the primary prevention of coronary heart disease.

Cholesterol lowering statin therapy accounted for over 10% of total drug acquisition costs (87.5 million euros) under the Community Drugs Schemes in Ireland in 2004. Not surprisingly, the issue of value for money and cost effectiveness arises. Whilst statin therapy has proven cost effective in patients with established cardiovascular disease this is the first economic evaluation of statin therapy for primary prevention in the Irish healthcare setting. Using economic modelling techniques the incremental cost effectiveness of statin therapy in high risk individuals i.e. 10 year risk exceeding 15% ranged from 17,900 euros per life year gained (LYG) to 33,800 euros/LYG under the GMS scheme. Corresponding figures for the Drug Payment scheme were 24,500 euros/ LYG to 48,500 euros/LYG. All the statins could be considered cost effective i.e. threshold below 50,000 euros/LYG however atorvastatin proved the most cost effective statin in this pharmacoeconomic study.

Coronary Disease↗

PubMed2006

Statins: the next anti-endotoxin.

Sepsis continues to be a major cause of morbidity and mortality. Evidence is emerging from observational studies and basic science research that statins (3-hydroxy, 3-methylglutaryl coenzyme A [HMG CoA] reductase inhibitors) might be associated with reduced mortality in sepsis. Statins have become the most widely used drugs for lowering serum cholesterol levels, being used by at least 15% of patients requiring admission to hospital, and this number is growing each year. Current prescribing information suggests withholding statin therapy in acutely ill patients for fear of serious side effects. However, statins have been postulated to have beneficial effects independent of their lipid-lowering effects, including anti-inflammatory and immunomodulatory roles. This review discusses the basis of these observations and the current place of statin therapy in patients with sepsis. This is a rapidly growing field of fascinating experimental biology. It suggests an urgent need to investigate the pharmacology of these drugs and reappraise their therapeutic indications in critically ill patients. This may provide new insights into the role of lipids and the endothelium in sepsis. Statins are significantly cheaper than other therapies that have been shown to improve outcome in sepsis, and the demonstration of a mortality benefit would have enormous cost-benefit implications.

Humans↗

PubMed2006

[Statins and cardiovascular diseases].

Statins are utilised in the primary and secondary prevention of coronary heart disease, due to their efficacy at lowering lipid levels. However, statins may also prevent atherosclerosis disease by non-lipid or pleiotropic effects, for example, improving endothelial function by promoting the production of NO. By increasing NO production, statins may interfere with atherosclerosis lesion developement, stabilise plaque, inhibit platlet aggregation, improve blood flow and protect against ischaemia. Therofore, the ability of statins to improve endothelial function through the release of NO may partialy account for their beneficial effects at reducing the incidence of cardiovascular events. Other pleiotropic effects of statins, i.e. immunomedulatory, antiinflammatory, antioxidant and antiendothelin effects, also contribute to the reduction of the incidence of major cardiovascular events. Statins have become the basic drugs in high risk cardiovascular patients with hypercholesterolemia. The ATP III update recommends an optional therapeutic target of LDL-C < 1,8 mmol/L in very high risk patients: those with acute coronary syndrome or those with CHD plus diabetes, the metabolic syndrome, multiple-risk factors, or a poorly controlled risk factor. Studies have demonstrated benefit from lipid lowering irrispective of initial LDL-C levels, including those with average levels at baseline.

Atherosclerosis↗

PubMed2006

An assessment of statin safety by neurologists.

The National Lipid Association's (NLA) Statin Safety Task Force charged the Neurology Expert Panel with the task of reviewing the scientific evidence related to adverse effects with statins and providing assessments and advice regarding the safety of statins. The evidence included key adverse reaction statin literature identified via a Medline search by the Task Force and Panel members and the commissioned reviews and research presented in this supplement. Panel members were asked to use this evidence to independently form explicit answers to a series of questions posed by the Task Force. Panelists were asked to grade the type of literature and the confidence they had in it in forming their answers using prescribed scales. Panelists were encouraged to seek the highest level of evidence available to answer their questions and to concentrate on literature involving humans. In addition, the Neurology Expert Panel was asked to propose recommendations to regulatory authorities, health professionals, patients, researchers, and the pharmaceutical industry to address statin safety issues.

Cognition↗

PubMedDate not supplied

Clinical outcomes in statin treatment trials: a meta-analysis.

OBJECTIVE: To determine the risk of cardiovascular events and death in patients receiving statin treatment for cholesterol regulation. METHODS: Systematic review and meta-analysis of all randomized controlled trials that were published as of April 15, 1997. Primary or secondary prevention trials or regression trials were eligible. MAIN OUTCOME MEASURES: All-cause mortality, fatal myocardial infarction (MI) or stroke, nonfatal MI or stroke, angina, and withdrawal from the studies. Both random- and fixed-effects models were run for the outcomes of interests, and results are expressed as odds ratios (ORs). Sensitivity analyses tested the impact of the study type and duration, statin treatment type, and control arm event rates. Intent-to-treat denominators were used whenever they were available, and the number needed to treat was calculated when appropriate. RESULTS: Seventeen studies (21 303 patients) were included (2 secondary prevention studies, 5 mixed primary-secondary prevention population studies, and 10 regression trials). Treatment groups included lovastatin (t = 5), pravastatin (t = 10), and simvastatin (t = 3). For all-cause mortality, the OR was 0.76 (95% confidence interval [CI], 0.67-0.86) in favor of receiving statin treatment; for fatal MI, the OR was 0.61 (95% CI, 0.48-0.78); for nonfatal MI, the OR was 0.69 (0.54-0.88); for fatal stroke, the OR was 0.77 (95% CI, 0.57-1.04); for nonfatal stroke, the OR was 0.69 (95% CI, 0.54-0.88); and for angina, the OR was 0.70 (95% CI, 0.65-0.76). CONCLUSIONS: Patients who received statin treatment demonstrated a 20% to 30% reduction in death and major cardiovascular events compared with patients who received placebo. This advantage was generally present across study types and statin treatment types and for patients with less severe dyslipidemias. The benefit in clinical outcomes was noticeable as early as 1 year.

Anticholesteremic Agents↗

PubMed2002

Statin use, bone mineral density, and fracture risk: Geelong Osteoporosis Study.

BACKGROUND: Recent data suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease fracture risk and increase bone mineral density (BMD). METHODS: This cross-sectional study is set in southeastern Australia. We evaluated the association between statin use, fracture risk, and BMD in 1375 women (573 with incident fractures and 802 without incident fracture, all drawn from the same community). Fractures were identified radiologically. Medication use and lifestyle factors were documented by questionnaire. RESULTS: Unadjusted odds ratio for fracture associated with statin use was 0.40 (95% confidence interval [CI], 0.23-0.71). Adjusting for BMD at the femoral neck, spine, and whole body increased the odds ratio to 0.45 (95% CI, 0.25-0.80), 0.42 (95% CI, 0.24-0.75), and 0.43 (95% CI, 0.24-0.78), respectively. Adjusting for age, weight, concurrent medications, and lifestyle factors had no substantial effect on the odds ratio for fracture. Statin use was associated with a 3% greater adjusted BMD at the femoral neck (P =.08), and BMD tended to be greater at the spine and whole body but did not achieve statistical significance. CONCLUSION: The substantial 60% reduction in fracture risk associated with statin use is greater than would be expected from increases in BMD alone.

Aged↗