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PubMed1991

Isoproterenol downregulation of statin-related gene expression in the rat parotid gland.

Statin, a 57 kilodalton (kDa) nuclear protein, is characteristically found in nonproliferating cells in culture as well as nondividing cells of a wide range of highly differentiated tissues. Moreover, cells in culture that are statin positive lose this statin expression when re-entering the cell-cycle traverse. In this work, statin expression was investigated in the parotid gland of untreated rats and those treated with isoproterenol (IPR), a proliferation-inducing catecholamine. Indirect immunofluorescence microscopy revealed specific nuclear staining with anti-statin monoclonal antibody (S-44) in the acinar and ducts cells of the untreated rats but significantly reduced in those induced with isoproterenol. To characterize the protein recognized by S-44, protein extracts from both tissues were immunoblotted and incubated with S-44. The antibody reacted specifically with a 48 kDa protein in the extract of the parotid glands from untreated rats while no reaction was detected in that of the proliferation-induced ones. These observations along with the result that a statin-like (S1) transcript is downregulated by isoproterenol in the parotid glands further support the notion that the disappearance of statin-related expression is associated with the IPR-induced proliferation in the rat parotid glands. The discrepancy between the apparent molecular mass of the protein identified by S-44 in nonproliferating parotid cells and that of statin originally found in fibroblasts, suggests that either a modified form of statin may be present in the parotid gland, or this 48 kDa protein may be a member of the nonproliferative statin-like family.

Animals↗
PubMedDate not supplied

Potential nontraditional applications of statins.

OBJECTIVE: To review the current evidence for use of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) in nontraditional lipid-related applications, including acute coronary syndromes, peripheral arterial disease, stroke, and renal disease, and to describe ongoing trials evaluating the role of statins in these conditions. DATA SOURCES: Clinical literature was identified by a MEDLINE search (1990-November 2002) using >/=1 of the following search terms: acute coronary syndrome(s), angina pectoris, atherosclerosis, atorvastatin, clinical trials, diabetes mellitus, end-stage renal disease, fluvastatin, lovastatin, myocardial infarction, peripheral arterial disease, pravastatin, simvastatin, statins, and stroke. Treatment guidelines issued by professional and governmental organizations, such as the American Diabetes Association, American Heart Association, National Cholesterol Education Program, National Kidney Foundation, and National Stroke Foundation, were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles identified from the data sources were included if they pertained to the conditions described in the objectives and provided unique information concerning use of statins. DATA SYNTHESIS: Substantial evidence exists for the use of statins in acute coronary syndromes. Meta-analyses of data from major clinical trials indicate that statins prevent first and recurrent stroke, and large-scale trials are underway to evaluate the efficacy of statins in this setting. Accumulating evidence suggests that statins may be beneficial in reducing the morbidity and mortality associated with peripheral arterial disease and end-stage renal disease, and results from ongoing trials may confirm these benefits. Statins may also have a future role in amelioration of other conditions associated with atherosclerosis, such as diabetes mellitus. CONCLUSIONS: A large body of evidence supports the evaluation of statins in clinical settings beyond primary and secondary prevention of morbidity and mortality associated with coronary atherosclerosis.

Arterial Occlusive Diseases↗
PubMed2005

Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect.

BACKGROUND: Clinical trials have shown the benefits of statins after acute myocardial infarction (AMI). However, it is unclear whether different statins exert a similar effect in reducing the incidence of recurrent AMI and death when used in clinical practice. METHODS: We conducted a retrospective cohort study (1997-2002) to compare 5 statins using data from medical administrative databases in 3 provinces (Quebec, Ontario and British Columbia). We included patients aged 65 years and over who were discharged alive after their first AMI-related hospital stay and who began statin treatment within 90 days after discharge. The primary end point was the combined outcome of recurrent AMI or death from any cause. The secondary end point was death from any cause. Adjusted hazard ratios (HRs) for each statin compared with atorvastatin as the reference drug were estimated using Cox proportional hazards regression analysis. RESULTS: A total of 18,637 patients were prescribed atorvastatin (n = 6420), pravastatin (n = 4480), simvastatin (n = 5518), lovastatin (n = 1736) or fluvastatin (n = 483). Users of different statins showed similar baseline characteristics and patterns of statin use. The adjusted HRs (and 95% confidence intervals) for the combined outcome of AMI or death showed that each statin had similar effects when compared with atorvastatin: pravastatin 1.00 (0.90-1.11), simvastatin 1.01 (0.91-1.12), lovastatin 1.09 (0.95-1.24) and fluvastatin 1.01 (0.80-1.27). The results did not change when death alone was the end point, nor did they change after adjustment for initial daily dose or after censoring of patients who switched or stopped the initial statin treatment. INTERPRETATION: Our results suggest that, under current usage, statins are equally effective for secondary prevention in elderly patients after AMI.

Aged↗
PubMed2005

Low myopathy rates associated with statins as monotherapy or combination therapy with interacting drugs in a group model health maintenance organization.

STUDY OBJECTIVE: Because the risk for myopathy increases when 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) are used with other agents known to inhibit cytochrome P450 3A4 in patients with dyslipidemia, we sought to quantify this risk in a diverse, real-world sample of patients receiving statin therapy. DESIGN: Retrospective chart review. SETTING: Kaiser Permanente Colorado (KPCO), a group model health maintenance organization with approximately 360,000 members. PATIENTS: Four hundred sixty-eight patients who were identified as having a diagnosis of myopathy over a 4-year period using KPCO computerized data systems. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed to confirm myopathy cases associated with statin therapy. Of the 468 patients, 61 had received statin therapy before their diagnosis, and 41 (67%) of these patients had confirmed myopathy (documented creatine kinase level>or=1000 IU/L). The prevalence of myopathy was 0.12% with statin monotherapy and 0.22% with statins in combination with interacting drugs. Only 17 of the 41 (41%) patients had confirmed myopathy with no other plausible clinical explanation, such as a muscle injury. Increased risk of myopathy associated with statin therapy in combination with interacting drugs approached statistical significance (p=0.052) but was of minimal clinical significance. CONCLUSION: The prevalence of confirmed myopathy in patients receiving statin therapy is low (<1%). Combining statin therapy with interacting drugs (e.g., fibrates) was not associated with a clinically important increase in the prevalence of myopathy. The risk of developing myopathy during statin therapy is outweighed by the benefits derived from the therapeutic effects of the therapy.

Adult↗
PubMed2006

Statin use and tooth loss in chronic periodontitis patients.

BACKGROUND: Statins have anti-inflammatory and bone stimulating properties that may positively affect chronic periodontitis. Our objective in this study was to evaluate whether statin use by chronic periodontitis patients had a beneficial impact on tooth loss. METHODS: In a retrospective cohort study (N patients = 1,021; mean follow-up = 7.1 years), dental records were merged with pharmacy data. Any statin use during 3 years, statin use during each of 3 consecutive years (regular use), and any statin use during the first 3 years after the initial periodontal exam were evaluated as predictors of tooth loss using negative binomial regression models with adjustment for potential confounding factors. RESULTS: Any statin use during 3 years was not associated with tooth loss rate in the year subsequent to the 3-year period (rate ratio [RR] = 1.00; 95% confidence interval [CI] = 0.56 to 1.81). Regular statin use during 3 years was associated with a non-significant 37% reduced tooth loss rate in the year subsequent to the 3-year period (RR = 0.63; 95% CI = 0.32 to 1.25). Any statin use during the first 3 years after the initial periodontal exam was associated with a 48% decreased tooth loss rate in year 4 and subsequent years (RR = 0.52; 95% CI = 0.29 to 0.95). CONCLUSIONS: Our findings were mixed for an association of statin use with reduced tooth loss in chronic periodontitis patients. Lack of control for some potential confounders, particularly smoking, and evaluation of different patterns of statin usage hamper the interpretation of the results. Exploration of these findings in additional epidemiological studies may be worthwhile.

Adult↗
PubMed2006

Thienopyridines and statins: assessing a potential drug-drug interaction.

Clopidogrel and statins are frequently administered in patients with ischemic heart disease or other atherothrombotic manifestations and are effective in the prevention of cardiovascular disease. The thienopyridine clopidogrel is a pro-drug metabolised in the liver via the cytochrome P450 (CYP) 3A4 system to the active compound which inhibits the P2Y(12) ADP platelet receptor. The assumption exists that the effect of clopidogrel in inhibiting platelet aggregation is attenuated by co-administration of lipophilic statins such as atorvastatin or simvastatin which are metabolised by the CYP3A4 system to inactive substrates. Assessing a possible drug-drug interaction ex-vivo, inconclusive studies have been published: In an aggregometer study, a strong and dose-dependent interference between atorvastatin and the inhibitory effect of clopidogrel on platelet function was observed. Another study, measuring the effect of clopidogrel by flow cytometry, found a significant attenuation of the clopidogrel effect by lipophilic statins, predominantly in the loading phase. In contrast a recent study, which used 600 mg clopidogrel for loading, found no significant interference between various statins and clopidogrel on ADP-induced platelet aggregation and in addition another study revealed no attenuation of the clopidogrel effect despite statin co-medication after 5 weeks. Additionally, retrospective analysis of clinical studies (CREDO-study) or registries (MITRA-PLUS) revealed no significant influence of different statins on the clinical outcome in patients treated with clopidogrel. However, these clinical studies showed a trend towards a diminishing effect of clopidogrel on those treated with cytochrome CYP3A4 metabolised statins. Even more important seems to be the considerable variability in the response of the antiplatelet effect of clopidogrel. A certain percentage of patients apparently do not respond adequately to clopidogrel treatment. This effect of clopidogrel resistance seems to be more important as the potential interference between CYP3A4 metabolized statins and clopidogrel. Finally, up until now sufficient evidence has not been gained to prefer hydrophil statins on patients receiving clopidogrel co-medication or when to discontinue the use of statins in clopidogrel treatment. Prospective studies are necessary in order to evaluate the magnitude of clopidogrel resistance and the impact of clopidogrel co-medication as well as to redefine antithrombotic therapy for this subgroup.

Animals↗
PubMed2006

Statins for diabetic cardiovascular complications.

The prevalence of diabetes mellitus (DM), particularly Type 2 DM, has rapidly increased in industrialized and many developing countries. The predominant cause of death in diabetic patients is vascular complications. Dyslipidemia and hypercholesterolemia are common in diabetic patients. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) were designed for lowering cholesterol synthesis. Landmark clinical trials indicated that statins effectively reduced cardiac death and events in patients with coronary artery disease or DM. The benefits of statins on the prevention of vascular events were independent from age, sex or baseline lipid levels in diabetic patients. Statins not only prevent atherosclerotic macrovascular complications, but also postpone the development of microvascular complications of DM, such as nephropathy and retinopathy. The non-cholesterol lowering or pleiotropic effects of statins have attracted vast attention. Results from experimental and clinical studies suggest that statins may attenuate inflammation, oxidative stress, coagulation, platelet aggregation, and improve insulin resistance, fibrinolysis and endothelial functions and help to prevent thrombosis, restenosis or organ transplantation rejection. Statins may affect the intracellular prenylation of proteins, which modulate the activity of small-GTP binding proteins. This may be an underlying mechanism for some pleiotropic effects of statins. Statins have an excellent safety profile and seldom cause adverse effects. Increasing evidence suggests that statins are the current treatment of choice to prevent vascular complications in diabetic patients with hypercholesterolemia.

Aged↗
PubMed2001

Synthetic statins: more data on newer lipid-lowering agents.

Extensive trial evidence supports the use of hydroxy-methyl-glutaryl-CoA reductase inhibitors (HMG-CoA-RI; statins) in atherosclerotic disease. Statins can be divided into two broad groups: the 'natural' statins derived from a fungal metabolites, and synthetic compounds. Whether all statins have similar anti-atherosclerotic properties, or whether these actions are specific to the 'natural' statins, is controversial. This commentary reviews the differences between natural and synthetic statins with regard to lipid-lowering and non-lipid-lowering effects, including their action on the acute phase reactant C-reactive protein. Among the newer synthetic statins, fluvastatin has some positive end-point evidence while cerivastatin shares many biochemical properties with the 'natural' statins. Extensive clinical trial programmes are underway with both atorvastatin and cerivastatin. These trials will give a definitive answer to the question of whether synthetic statins are as equally efficacious as 'natural' statins in preventing atherosclerotic events.

Arteriosclerosis↗
PubMed2003

[Long-term treatment with statins in patients with ischemic heart disease after coronary angioplasty].

UNLABELLED: Long-term statin therapy is the corner-stone in management of patients with coronary artery disease. PURPOSE OF STUDY: The aim of our study was to analyze the state of the statin therapy at patients undergoing percutaneous coronary intervention (PCI) and to determine predictors of long-term statin treatment. METHODS: We performed a retrospective study in 520 patients who underwent percutaneous coronary angioplasty in 2nd Dept. of Internal Medicine, 1st School of Medicine, Charles University, Prague during the year 2000. Data were collected from hospital records and from a mailed questionnaire. RESULTS: The response rate was 61.9% and the average response time was 11.6 +/- 3.5 months after PCI. Long-term statin therapy was prescribed in 52.5%. In patients with hypercholesterolemia 67.1% were treated in comparison with 32.3% treated patients without this diagnosis (p < 0.0001). Patients aged 70 years and older were treated significantly less frequently then younger individuals (30.6% vs. 61.3%, p < 0.0001). Patients with a history of prior revascularization procedure were treated significantly more often then patients undergoing the first procedure (64.8% vs. 49.8%, p < 0.05). Multivariate logistic regression analysis was applied to detect significant predictors of long-term statin therapy. Only hypercholesterolemia and statin prescription at discharge were identified as independent positive predictors, whereas age > or = 70 years and male gender had negative predictive value. CONCLUSION: By course of evidence-based medicine, patients who underwent PCI in our study are undertreated by statins. Statin treatment should be initiated in all patients treated by PCI with increased cardiovascular risk. Patients at defined risk for undertreatment are mainly older patients and men. The prescription of statin therapy at the time of hospital discharge appears to be a very effective tool to improve long-term statin therapy.

Aged↗
PubMedDate not supplied

Clinical pharmacokinetics of statins.

This article reviews the pharmacokinetic properties of HMG-CoA reductase inhibitors (or statins), as reported in humans. Most data presented here refer to commercially available statins (atorvastatin, fluvastatin, lovastatin and simvastatin), although statins that have recently been withdrawn (cerivastatin) or are currently under development (glenvastatin, pitavastatin and rosuvastatin) will also be considered. All statins with the exception of pitavastatin show very low systemic bioavailability due to an extensive first pass effect at the intestinal and/or hepatic level. Such a characteristic can be advantageous, since the liver is the target organ for statins. Unlike most statins, lovastatin and simvastatin are administered as inactive lactone prodrugs. Statins differ mainly in the degree of metabolism and the number of active and inactive metabolites. All statins but pravastatin show highly active metabolites, the pharmacological activity depending on the kinetic profile of both parent compound and active metabolites. Pravastatin has the lowest protein binding (50% vs. > 90%) and is eliminated by both metabolism and renal excretion. Atorvastatin shows the longest terminal half-life (11-14 h vs. 1-3 h). Pharmacokinetic interactions with statins are very likely to occur, particularly for those statins that are CYP3A4 substrates. However, although of extreme interest in clinical practice, this subject was extensively reviewed in a previous article and therefore is not discussed here.

Administration, Oral↗
PubMed2003

Potential antitumor effects of statins (Review).

Statins, which have been introduced to the clinic for the treatment of hypercholesterolemia, are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the major rate-limiting enzyme that controls the conversion of HMG-CoA to mevalonic acid (MA). MA is the precursor in the biosynthesis of isoprenoid compounds including cholesterol, dolichol and ubiquinone. Furthermore, mevalonate-derived prenyl groups enable precise cellular localization and function of many proteins such as Ras and Rho proteins. Therefore, besides lowering cholesterol level, statins exert pleiotropic effects on many essential cellular functions including cell proliferation, differentiation, and survival but also participate in the regulation of cell shape and motility. Statins have been shown to inhibit proliferation and to induce apoptosis in a variety of tumor cells. They have also been found to display antitumor effects against melanoma, mammary carcinoma, pancreatic adenocarcinoma, fibrosarcoma, glioma, neuroblastoma, and lymphoma in animal tumor models resulting in retardation of tumor growth, and/or inhibition of the metastatic process. In preclinical studies statins have also been demonstrated to potentiate the antitumor effects of some cytokines and chemotherapeutics. The molecular mechanisms underlying antitumor activity of statins have not been fully elucidated but interference with the function of Ras and Rho family GTPases, inhibition of the activity of certain cyclin-dependent kinases (CDK), and activation of CDK inhibitors, all seem to participate in this activity. The results of several clinical studies of statins in cancer patients including phase I, phase I/II, and phase II trials have been published. Although evaluation of the therapeutic efficacy is not the purpose of early clinical trials and all conclusions might be premature at this stage, some preliminary conclusions have already been drawn. The results of these studies do not show any significant therapeutic effects of statins in cancer patients. However, the results of one of these studies suggest that statins could effectively strengthen the therapeutic activity of some chemotherapeutics. This observation seems to agree with the results of preclinical studies. However, as toxic side effects of statins have been particularly evident in their combination with some other drugs great caution should be advised while planning clinical trials based on combination therapy including statins in cancer patients.

Animals↗
PubMed2003

A qualitative study of barriers to the use of statins and the implementation of coronary heart disease prevention in primary care.

BACKGROUND: Statin prescribing to prevent coronary heart disease is well below recommended levels. Studies suggest that the prescribing behaviour of doctors may be the biggest factor in the wide variation in statin prescribing in general practice. Understanding doctors' perceptions offers some insight into why variation occurs. AIM: To understand general practitioners' (GPs') views about barriers to statin prescribing, statin prescribing guidelines, and the successes and barriers to coronary prevention in primary care. DESIGN OF STUDY: Qualitative analysis of semi-structured interviews. SETTING: General practices in mid and south Bedfordshire. METHOD: Interviews with 26 GPs. RESULTS: GPs spoke of a variety of barriers to initiating statin treatment specifically, and coronary heart disease prevention generally. Barriers to statin prescribing included: concerns about cost; increased workload and adherence to treatment; variation in treatment targets for lowering cholesterol; and concerns about medicalisation, lifestyle, and health behaviour. GPs found it difficult to prioritize patients for statin treatment, their statin treatment targets varied, and many found primary prevention risk assessment tools difficult to interpret. Coronary prevention was limited by practice space and organisational issues, by problems with recording and retrieval of electronic data, and by limited doctor and nurse time. GPs suggested that funded nurse time, nurse-led heart disease clinics, and better use of electronic data would improve primary care coronary prevention. CONCLUSION: There are complex barriers to statin prescribing and coronary prevention in general practice, which may explain some of the variation that exists. Further studies of patients' views of statins may provide more information. More resources, improved guidance, and better dissemination of guidance may only address some of the issues.

Attitude of Health Personnel↗
PubMed2005

Cholesterol levels and statin use in patients with coronary heart disease treated in primary care settings.

INTRODUCTION: Therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, has proven to be effective in the treatment of lipid disorders. However, statin therapy continues to be underused, even though statins are a relatively safe and well-tolerated class of agents. In this study, we assessed trends in lipid control in patients with heart disease who receive most of their health care in primary care clinics. The objective was to determine whether systems of care implemented within a large medical group are associated with improved treatment and control of dyslipidemia in a high-risk group of coronary heart disease patients. METHODS: All adults with heart disease in a Minnesota medical group (N = 2947) were identified using diagnosis and procedure codes related to coronary heart disease (sensitivity = 0.85; positive predictive value = 0.89) in 1996. Study subjects were observed from 1995 to 1998. Subjects had a baseline and follow-up test for low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Changes between baseline and follow-up measurements and trends in the use of statins and other lipid-active agents among the study subjects were analyzed. RESULTS: Among 1388 subjects with two or more eligible lipid measurements, mean low-density lipoprotein cholesterol improved from 137.6 mg/dL to 111.0 mg/dL (P < .001), and mean high-density lipoprotein cholesterol improved from 42.3 mg/dL to 46.3 mg/dL (P < .001). The percentage of patients with low-density lipoprotein cholesterol < or = 100 mg/dL rose from 12.5% to 39.8% (P < .001), and the percentage with high-density lipoprotein cholesterol > or = 40 mg/dL rose from 52.5% to 67.6% (P < .001). In multivariate models, statin use was identified as the main factor that contributed to the improvement in low-density lipoprotein cholesterol (P < .001). Men had greater decreases in low-density lipoprotein cholesterol than women after adjusting for other variables (P < .001). Statin use rose from 24.3% at baseline to 69.6% at follow-up. The statin discontinuation rate was 8.3% for baseline statin users and 12.2% for subjects who used statins at any time during the study period. CONCLUSION: Investment in better heart disease care for patients in primary care clinics led to major improvement in lipid control over 30 months, primarily due to increased statin use. Improvements in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were sufficient to substantially reduce risk of subsequent major cardiovascular events.

Aged↗
PubMed2006

An assessment of statin safety.

Recently, statin safety and potential drug interactions have received close attention in the consumer and medical press. In particular, rosuvastatin, the most recent statin introduced into the US market, has been the object of much speculation. Many of these reports have lost sight of the proven efficacy of statins in coronary disease prevention at a time when coronary heart disease is the number one killer of adults, and have failed to frame the potential drug toxicity in the context of this benefit. Summarized here are the conclusions of the National Lipid Association's Statin Safety Assessment Task Force, which reviewed extensive new drug application (NDA) and postmarketing data for all the currently marketed statins regarding their effect on the liver, muscle, renal, and neurologic systems. The task force found that, overall, hepatic, renal, or neurologic function does not appear to be compromised by statin use. They do not recommend routine monitoring of these systems but do recommend ongoing surveillance of symptomatic patients. With respect to muscle toxicity, the task force's Muscle Expert Panel concluded that the incidence of myopathy and rhabdomyolysis is low and appears to be dose-related, rather than associated with the degree of low-density lipoprotein cholesterol lowering and also appears to be related to the individual statin used. For example, from the rosuvastatin NDA database and additional postmarketing data, the overall incidence of myopathy was found to be lower than that observed with other statins. Administrative claims data of hospitalization rates for adverse events in statin patients confirm the task force conclusion that, overall, statins are safe and well tolerated when used as monotherapy.

Advisory Committees↗
PubMed2006

Impact of statin copayments on adherence and medical care utilization and expenditures.

OBJECTIVE: To examine the effects of statin cost-sharing (ie, copayments, coinsurance) on adherence to statin medications and the impact of adherence on healthcare utilization and spending. STUDY DESIGN: Retrospective, observational study of statin users receiving health benefits or supplemental coverage from employer-sponsored health plans. METHODS: Medical and pharmacy claims were selected from the Medstat MarketScan database for patients who were continuously enrolled from 2000 through 2003. Two-stage residual inclusion models were estimated. The first stage modeled adherence to statins, which was derived from the medication possession ratio, and represented the percentage of days on therapy in an 18-month time frame, July 2001 through December 2002. In the second stage, generalized linear models were used to estimate 2003 utilization and expenditures. Separate estimates were produced for new statin users (n = 24 113) and continuing statin users (n = 93 253). RESULTS: Lower statin copayments were associated with higher levels of statin adherence. In percentage terms, when holding all other variables at their mean value, a $10 increase in copayment resulted in a 1.8 percentage point reduction in the probability of adherence for new users and a 3 percentage point reduction in the probability of adherence for continuing users. For continuing users adherent to statins, total costs did not change, but fewer negative events (emergency department visits, hospitalizations, and coronary heart disease-related hospitalizations) occurred. CONCLUSIONS: Policy makers and plan managers should consider interventions that improve adherence to statins, such as lower copayments.

Aged↗
PubMed2005

Expanding indications for statins in cerebral ischemia: a quantitative study.

BACKGROUND: New US Food and Drug Administration labeling in 2003 recognizes stroke and evidence of cerebrovascular disease as indicator conditions for initiating statin (simvastatin) therapy, based on results of the Heart Protection Study, thereby extending the indications for statins in stroke beyond current US and European guidelines. OBJECTIVE: To assess the impact on clinical practice of broadening indications for statins in patients with stroke. DESIGN: Observational study. SETTING: University hospital stroke service. PATIENTS: One hundred consecutive patients with ischemic stroke and transient ischemic attack. INTERVENTIONS: Development and application of algorithms for initiating statin therapy in patients with stroke and transient ischemia abstracted from recent national and international guidelines (National Cholesterol Education Program Adult Treatment Panel III, European Joint Task Force II), Heart Protection Study entry criteria, and Heart Protection Study-based US Food and Drug Administration labeling. MAIN OUTCOME MEASURES: Percentages of patients who met clinical trial-validated and US Food and Drug Administration-approved criteria for initiation of statin therapy. RESULTS: Patient age averaged 74 years (range, 35-96 years); 64% were female, and 74% were white. Stroke subtype was large-vessel atherosclerosis in 24%, cardioembolic in 44%, small-vessel atherosclerosis in 22%, and other in 10%. Twenty of 100 patients were already taking statins on admission. Guidelines for definite initiation of statin treatment were met by 48% of patients for the National Cholesterol Education Program III, 38% for the European Joint Task Force II, 92% for the Heart Protection Study, and 100% for the Food and Drug Administration. CONCLUSIONS: Most clinically encountered patients with ischemic stroke meet clinical trial-validated criteria for initiation of statin therapy. Rigidly applying current national and international guidelines may deprive up to one half of these patients of advantages of statin therapy.

Adult↗
PubMed2005

Statins and fibrates for preventing melanoma.

BACKGROUND: Effective treatment for advanced melanoma is lacking. While no drug therapy currently exists for prevention of melanoma, in vitro, case-control, and animal model evidence suggest that lipid-lowering medications, commonly taken for high cholesterol, might prevent melanoma. OBJECTIVES: To assess the effects of statin or fibrate lipid-lowering medications on melanoma outcomes. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (February 2003), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (to March 2003), EMBASE (to September 2003), CANCERLIT (to October 2002), Web of Science (to May 2003), and reference lists of articles. We approached study investigators and pharmaceutical companies for additional information (published or unpublished studies). SELECTION CRITERIA: Trials involving random allocation of study participants, where experimental groups used statins or fibrates and participants were enrolled for at least four years of therapy. DATA COLLECTION AND ANALYSIS: Three authors screened 109 abstracts of articles with titles of possible relevance. We then thoroughly examined the full text of 72 potentially relevant articles. We requested unpublished melanoma outcomes data from the corresponding author of each qualifying trial. MAIN RESULTS: We identified 16 qualifying randomised controlled trials (RCTs) (seven statin, nine fibrate). Thirteen of these trials (involving 62,197 participants) provided data on incident melanomas (six statin, seven fibrate). A total of 66 melanomas were reported in groups receiving the experimental drug and 86 in groups receiving placebo or other control therapies. For statin trials this translated to an odds ratio of 0.90 (95% confidence interval 0.56 to 1.44) and for fibrate trials an odds ratio of 0.58 (95% confidence interval 0.19 to 1.82). Subgroup analyses failed to show statistically significant differences in melanoma outcomes by gender, melanoma occurrence after two years of participation in trial, stage or histology, or trial funding. Subgroup analysis by type of fibrate or statin also failed to show statistically significant differences, except for the statin subgroup analysis which showed reduced melanoma incidence for lovastatin, based on one trial only (odds ratio 0.52, 95% confidence interval 0.27 to 0.99). AUTHORS' CONCLUSIONS: The melanoma outcomes data collected in this review of RCTs of statins and fibrates does not exclude the possibility that these drugs prevent melanoma. There was a 10% and 42% reduction for participants on statins and fibrates, respectively, however these results were not statistically significant. Until further evidence is established, limiting exposure to ultraviolet radiation remains the most effective way to reduce the risk of melanoma.

Anticholesteremic Agents↗
PubMed2004

Use of statins prior to percutaneous coronary intervention reduces myonecrosis and improves clinical outcome.

Primary and secondary prevention with statins reduce major cardiac events in patients with coronary artery disease. The impact of pretreatment with statins prior to percutaneous coronary intervention (PCI) is not well established. The objective of this study was to determine if pretreatment with statins prior to PCI reduce myonecrosis and improve clinical outcome. One hundred nineteen consecutive patients with acute coronary syndrome who underwent PCI were identified. We compared the incidence of myonecrosis defined as peak elevation of CK-MB or CK three time above upper limit of normal within 24 hr and the 6-month cardiovascular event rate (death, nonfatal myocardial infarction unrelated to PCI, target vessels revascularization, and unstable angina requiring hospitalization) among patients who received statins prior to PCI (n = 63) to those who did not (n = 56). Pretreated patients were more likely to have history of myocardial infarction or revascularization (63% vs. 43%; P = 0.015), hyperlipidemia (80% vs. 48%; P = 0.001), hypertension (83% vs. 49%; P = 0.02), and use of angiotensin-converting enzyme inhibitor (62% vs. 38%; P = 0.008). The rest of baseline characteristics were similar between the two groups, including use of glycoprotein IIb/IIIa inhibitors, number of diseased vessels, and type of lesions. Patients pretreated with statins had a significantly lower incidence of myonecrosis (2% vs. 10%; P = 0.04) at 24 hr and a significantly lower clinical event (CE) rate at 6 months (17% vs. 21%; P = 0.015). Of patients not pretreated with statins, 72% were taking statins at 6 months as compared to 98% of pretreated patients. After adjusting for all baseline characteristics, use of statins prior to PCI was associated with a marked decrease in risk of all CEs (OR = 0.2; CI = 0.06-0.63; P = 0.006). Statin therapy prior to PCI may reduces peri-PCI myonecrosis and late cardiac events. These results need to be confirmed in large prospective randomized trials.

Angioplasty, Balloon, Coronary↗